Streptococci

Diagn Microbiol Infect Dis, 2002 Nov, 44(3), 213 - 20
Microbiology of newer fluoroquinolones: focus on respiratory pathogens; Jones RN; Community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute sinusitis are among the most common bacterial infections encountered in clinical practice . Pathogens frequently associated with these infections include Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae . Unfortunately, resistance to antimicrobials commonly used for the treatment of these infections is increasing, limiting the clinical efficacy of these agents . Fluoroquinolones offer several advantages over other classes of antimicrobials used for the treatment of community-acquired respiratory tract infections . In general, fluoroquinolones have excellent in vitro activity against common respiratory pathogens, including some drug-resistant strains of S . pneumoniae . Microbial resistance to the newer fluoroquinolones is relatively uncommon, currently occurring in approximately 1% of clinical isolates in North America . Fluoroquinolones currently in clinical development may offer additional benefits over the marketed agents because they maintain good potency against isolates of S . pneumoniae displaying resistance to older quinolones (i.e., ofloxacin or ciprofloxacin) and may have a lower potential to engender resistance . This article reviews the in vitro activity of several newer fluoroquinolones, including agents currently in clinical development, against common respiratory pathogens, including antimicrobial-resistant strains . The mechanisms and prevalence of resistance of beta-lactam antimicrobials, macrolides, and fluoroquinolones also are reviewed.

Nippon Jibiinkoka Gakkai Kaiho, 2002 Nov, 105(11), 1143 - 6
{A case of spinal epidural abscess associated with retropharyngeal abscess}; Fujiyoshi T et al.; Spinal epidural abscesses are known to occur associated with retropharyngeal abscess, but such cases are few in the literature . We treated a 72-year-old woman who reported pain in the back of the neck . Computed tomography (CT) showed a retropharyngeal abscess extending to the upper neck through the carotid space on the left side and an magnetic resonance imaging (MRI) showed a spinal epidural abscess without cervical vertebral osteomyelitis . The abscess was assumed to reach the epidural space along the nerve root through the intervertebral foramen . Since tonsillitis appeared to cause the retropharyngeal abscess, we performed tonsillectomy, and then drained pus through the superior constrictor muscle, effecting a subsequent cure . Staphylococcus aureus was recovered from both the pus and tonsil, and Streptococcus constellatus, a member of the Streptococcus milleri group, from the tonsil . Based on a review of the literature, clinical courses of spinal epidural abscess associated with retropharyngeal abscess are not always simple, as 4 of the 7 cases found demonstrated poor prognosis . Spinal epidural abscess should be considered a critical complication of retropharyngeal abscess.

Strahlenther Onkol, 2002 Dec, 178(12), 722 - 6
Sparing of contralateral major salivary glands has a significant effect on oral health in patients treated with radical radiotherapy of head and neck tumors; Beer KT et al.; BACKGROUND: Has a conscious exclusion of the contralateral major salivary glands (parotid, submandibular, and sublingual glands) a significant impact on the milieu of the oral cavity (saliva flow, pH, buffer capacity, and colonisation with Streptococcus mutans) in patients with ENT tumors receiving radical radiotherapy? PATIENTS AND METHODS: 20 consecutive consenting patients with ENT tumors were evaluated once before, weekly during, and 6 weeks after the end of treatment in regard to saliva flow, ph, buffer capacity, and colonisation with Streptococcus mutans . In 13 patients the major salivary glands on both sides were included in the treated volume, in seven patients the treatment portals excluded consciously the contralateral major salivary glands . RESULTS: The stimulated saliva flow decreases already during the 1st week of radiotherapy, the decrease follows the dose exponentially; the saliva flow is further reduced in the weeks after the end of treatment . The effect is less pronounced in patients with sparing of contralateral major salivary glands . The majority of patients with unilateral sparing of the major salivary glands retain the baseline value of buffer capacity, whereas buffer capacity of all patients with inclusion of all major salivary glands is markedly reduced with 20 Gy already, without signs of recovery when treatment has stopped . With unilateral salivary gland sparing the pH always remains basic, in bilaterally irradiated patients the pH changes from a mean of 7.3 to 5.8 during treatment . The colonisation with Streptococcus mutans varies little in both groups during the radiotherapy; after the end of therapy, it is higher in bilaterally irradiated patients . CONCLUSIONS: The conscious arrangement of irradiation portals in order to spare contralateral major salivary glands in patients with radical radiotherapy of ENT tumors has a significant influence on the oral environment: the stimulated saliva flow is higher, the buffer capacity retains the baseline value, the saliva pH remains basic, and the colonisation with Streptococcus mutans is reduced.

Pathol Biol (Paris), 2002 Nov, 50(9), 560 - 4
{Antibiotics resistance of Streptococcus pneumoniae . Results from the Brittany registry for 1999}; Desbordes L et al.; Throughout 1999, clinical microbiology laboratories of 13 hospitals in Brittany have recovered Streptococcus pneumoniae isolates in 832 patients, 312 (37.5%) female and 518 (62.2%) male . Two hundred fifty five of them (30.6%) were children . One hundred eighty eight isolates were recovered from blood cultures (22.6%), 16 from CSF (1.9%), 449 from lungs (54%), and 88 from ear exsudates (10.6%).A 5 microgram oxacillin-disk test was used to detect isolates with reduced susceptibility to penicillin G . Determination of MICs of penicillin G, amoxicillin and cefotaxime were then performed by agar dilution method on 402 strains previously categorized resistant or intermediate.Five hundred forty six isolates were PSDP, 33.5% of them were resistant to penicillin G, 2.2% to amoxicillin and 0.2% to cefotaxime . As expected, a decreased susceptibility to beta-lactamins was frequently associated with resistance to macrolides, cotrimoxazole and tetracycline . Among PSDP, the most prevalent serotypes were 23 (23.7%), 14 (23.5%) and 19 (19.1%).In Brittany, the constant rise of PSDP (1993-1994: 28.5%; 1997: 56.4%; 1999: 65.6 %) could be perhaps explain by analysis of social and demographic data.

Pediatr Nephrol, 2003 Jan, 18(1), 39 - 45 Epub 2002 Nov 22.
Oral health in children with chronic renal failure; Al-Nowaiser A et al.; Seventy children with chronic renal failure (CRF) aged 4-13.6 years were recruited from the Renal Unit of the Great Ormond Street Hospital for Children . Indices were recorded for dental caries, dental plaque, gingival inflammation, gingival enlargement, and enamel defects . Salivary urea, buffering capacity, and the oral streptococcal flora were determined for 25 of the children . A significantly greater proportion of the CRF children was caries free, 40% compared with 8.5% of the controls . The mean plaque score was significantly greater in the CRF group for both the primary 12.7 (16) and permanent dentition 22.0 (18.2) compared with the controls, 5.3 (7.6) and 15.5 (13.3), respectively . Eight CRF children had gingival enlargement . Enamel defects affecting the permanent teeth were observed in 57% of the CRF children compared with 33% of the controls . The buffering capacity was significantly greater in the CRF group, pH 6.4 (0.5) compared with the controls pH 5.6 (0.8) . The mean salivary urea level (mmol/l) was significantly greater in the CRF children, 11.6 (5.9) compared with 3.6 (1.4) for the controls . The isolation frequency of Streptococcus mutans was significantly greater from controls compared with the CRF children ( P=0.002) . An integrated dental service needs to be developed with emphasis on tooth brushing to prevent gingival hyperplasia and periodontal disease after puberty.

J Am Chem Soc, 2002 Dec 25, 124(51), 15368 - 74
Saturation transfer difference 1D-TOCSY experiments to map the topography of oligosaccharides recognized by a monoclonal antibody directed against the cell-wall polysaccharide of group A streptococcus; Johnson MA et al.; A new saturation transfer difference 1D-TOCSY NMR experiment that allows the investigation of complex ligands interacting with proteins and its application in the mapping of which portions of oligosaccharide ligands (epitope) interact with a complementary antibody are described . The interaction between trisaccharide and hexasaccharide ligands, corresponding to fragments of the cell-wall polysaccharide of Streptococcus Group A, and a monoclonal antibody directed against the polysaccharide is investigated at the molecular level . The polysaccharide consists of alternating alpha-(1-->2) and alpha-(1-->3) linked L-rhamnopyranose (Rha) residues with branching N-acetyl-D-glucopyranosylamine (GlcNAc) residues linked beta-(1-->3) to alternate rhamnopyranose rings . The epitope is proven to consist not only of the immunodominant GlcNAc sugar but also of an entire branched trisaccharide repeating unit . The experimental NMR data serve to check and validate the computed models of the oligosaccharide-antibody complexes.

Laryngorhinootologie, 2002 Dec, 81(12), 857 - 60
{Therapy of acute mastoiditis}; Michalski G et al.; BACKGROUND: Acute otitis media is a common disease, mostly contracted at childhood . The development of acute mastoiditis has been decreased since the introduction of antibiotics . Currently it is only developed in 0.004 % cases of acute otitis media . But despite of this fact, even today one should not neglect this condition as the complications such as intracranial spread and lateral sinus thrombosis are still life threatening . METHODS AND PATIENTS: In a retrospective study from 01/96 - 09/00 we reviewed the cases of acute mastoiditis as a result of acute otitis media at our department . Additionally we compared study results out of 1972 until 1989 with our current results . RESULTS: Altogether mastoidectomy has been carried out at 157 patients . The cases have steadily increased since 1996 . This is confirmed by comparison with study results of previous years . The majority of the patients were between 8 months and 3 years old (60 %) . When the patients first presented at our department, the first signs of otitis media were 19.5 days ago in average . 38 % of the patients received no antibiotic treatment before admission . A thickened mucous membrane was seen by the mastoidectomy mostly (58 %) . A subperiostal abscess we noted in 8.5 % . The most common isolated bacteria were Streptococcus pneumoniae (33 %) and Streptococcus pyogenes (11 %) . The patients stayed at the department about 10 days . In comparison to recent study results the "typical" mastoiditis has decreased . The causative pathogens have not changed . CONCLUSIONS: In the last years we realised an increasing number of mastoiditis at our department . The isolated bacteria are the same as presented in the literature . Early surgery combined with an effective antibiotic treatment can avoid the known complications of mastoiditis.

J Bacteriol, 2003 Jan, 185(1), 371 - 3
Choline starvation induces the gene licD2 in Streptococcus pneumoniae; Desai BV et al.; Mutant strains of Streptococcus pneumoniae were constructed to monitor the regulation of three dispersed genes known or predicted to act in choline metabolism . One gene (licD2) was regulated in response to choline deprivation over a 30-fold range . The other two (SP1860 and licC) responded little if at all to the same challenge.

J Bacteriol, 2003 Jan, 185(1), 359 - 70
Transcriptional regulation and signature patterns revealed by microarray analyses of Streptococcus pneumoniae R6 challenged with sublethal concentrations of translation inhibitors; Ng WL et al.; The effects of sublethal concentrations of four different classes of translation inhibitors (puromycin, tetracycline, chloramphenicol, and erythromycin) on global transcription patterns of Streptococcus pneumoniae R6 were determined by microarray analyses . Consistent with the general mode of action of these inhibitors, relative transcript levels of genes that encode ribosomal proteins and translation factors or that mediate tRNA charging and amino acid biosynthesis increased or decreased, respectively . Transcription of the heat shock regulon was induced only by puromycin or streptomycin treatment, which lead to truncation or mistranslation, respectively, but not by other antibiotics that block translation, transcription, or amino acid charging of tRNA . In contrast, relative transcript amounts of certain genes involved in transport, cellular processes, energy metabolism, and purine nucleotide (pur) biosynthesis were changed by different translation inhibitors . In particular, transcript amounts from a pur gene cluster and from purine uptake and salvage genes were significantly elevated by several translation inhibitors, but not by antibiotics that target other cellular processes . Northern blotting confirmed increased transcript amounts from part of the pur gene cluster in cells challenged by translation inhibitors and revealed the presence of a 10-kb transcript . Purine metabolism genes were negatively regulated by a homologue of the PurR regulatory protein, and full derepression in a DeltapurR mutant depended on optimal translation . Unexpectedly, hierarchical clustering of the microarray data distinguished among the global transcription patterns caused by antibiotics that inhibit different steps in the translation cycle . Together, these results show that there is extensive control of transcript amounts by translation in S . pneumoniae, especially for de novo purine nucleotide biosynthesis . In addition, these global transcription patterns form a signature that can be used to classify the mode of action and potential mechanism of new translation inhibitors.

J Bacteriol, 2003 Jan, 185(1), 349 - 58
Transient association of an alternative sigma factor, ComX, with RNA polymerase during the period of competence for genetic transformation in Streptococcus pneumoniae; Luo P et al.; Natural transformation in Streptococcus pneumoniae is regulated by a quorum-sensing system that acts through accumulation and sensing of a peptide pheromone (competence-stimulating peptide {CSP}) to control many competence-specific genes acting in DNA uptake, processing, and integration . The period of competence induced by CSP lasts only 15 min (quarter-height peak width) . The recently identified regulator ComX is required for the CSP-dependent expression of many competence-specific genes that share an unusual consensus sequence (TACGAATA) at their promoter regions . To test the hypothesis that this regulator acts as a transient alternative sigma factor, ComX was purified from an Escherichia coli overexpression strain and core RNA polymerase was purified from a comX-deficient S . pneumoniae strain . The reconstituted ComX-polymerase holoenzyme produced transcripts for the competence-specific genes ssbB, cinA, cglA, celA, and dalA and was inhibited by anti-ComX antibody, but not by anti-sigma(70) antibody . Western blotting using antibodies specific for ComX, sigma(70), and poly-His revealed a transient presence of ComX for a period of 15 to 20 min after CSP treatment, while RNA polymerase remained at a constant level and sigma(A) remained between 60 and 125% of its normal level . ComX reached a molar ratio to RNA polymerase of at least 1.5 . We conclude that ComX is unstable and acts as a competence-specific sigma factor.

J Bacteriol, 2003 Jan, 185(1), 60 - 70
The Streptococcus pneumoniae cia regulon: CiaR target sites and transcription profile analysis; Mascher T et al.; The ciaR-ciaH system is one of 13 two-component signal-transducing systems of the human pathogen Streptococcus pneumoniae . Mutations in the histidine protein kinase CiaH confer increased resistance to beta-lactam antibiotics and interfere with the development of genetic competence . In order to identify the genes controlled by the cia system, the cia regulon, DNA fragments targeted by the response regulator CiaR were isolated from restricted chromosomal DNA using the solid-phase DNA binding assay and analyzed by hybridization to an oligonucleotide microarray representing the S . pneumoniae genome . A set of 18 chromosomal regions containing 26 CiaR target sites were detected and proposed to represent the minimal cia regulon . The putative CiaR target loci included genes important for the synthesis and modification of cell wall polymers, peptide pheromone and bacteriocin production, and the htrA-spo0J region . In addition, the transcription profile of cia loss-of-function mutants and those with an apparent activated cia system representing the off and on states of the regulatory system were analyzed . The transcript analysis confirmed the cia-dependent expression of seven putative target loci and revealed three additional cia-regulated loci . Five putative target regions were silent under all conditions, and for the remaining three regions, no cia-dependent expression could be detected . Furthermore, the competence regulon, including the comCDE operon required for induction of competence, was completely repressed by the cia system.

Int J Food Microbiol, 2003 Mar 25, 81(3), 231 - 9
Rapid detection and identification of Streptococcus macedonicus by species-specific PCR and DNA hybridisation; Papadelli M et al.; The aim of this study was to develop a simple and specific method for the rapid detection and identification of Streptococcus macedonicus . The method was based on polymerase chain reaction (PCR) using species-specific primers derived from the 16S rRNA gene . Specific identification was proven on seven S . macedonicus strains, while 16 strains belonging to different lactic acid bacteria species were tested negative . The PCR assay was capable of detecting 100 pg of S . macedonicus DNA, and it was also efficient on single colonies of the bacterium . Furthermore, the same bacterial strains were used for the specificity evaluation of a S . macedonicus species-specific probe . Neither species-specific PCR nor DNA hybridisation experiments could differentiate Streptococcus waius from S . macedonicus, due to the identity of the 16S rRNA gene of the two species, indicating high phylogenetical relatedness . This was further confirmed by the comparative sequence analysis of the 16S-23S rRNA intergenic regions . It was thus clearly demonstrated that S . waius, recently described as a novel Streptococcus species, is phylogenetically identical to S . macedonicus.

J Vet Med B Infect Dis Vet Public Health, 2002 Dec, 49(10), 461 - 3
Epidemiological and bacteriological aspects of mastitis associated with yellow-jacket wasps (Vespula germanica) in a dairy cattle herd; Yeruham I et al.; The German wasp, Vespula germanica has been observed to injure teats of dairy cows, causing lesions that are associated with clinical and subclinical mastitis . The presence of skin lesions on the teats, caused by the wasps, was recorded in a dairy cattle herd located in the Samaria foothills during July-October 1999 . Wasp-inflicted injuries were found in 43.6% (58 of 133) of the adult cows and 1.4% (one of 71) of the first-calving cows . They were located in 42.4% of cows (n = 25) on all quarters, 18 cows (30.5%) had lesions on the front quarters and 27.1% (n = 16) of cows on the hind quarters only . Clinical and subclinical mastitis were diagnosed in 61% (36 of 59) and 28.8% (17 of 59), respectively, of the injured adult and first-calving cows . The most common bacterial isolates from the mastitic cows were Staphylococcus aureus 45.1% (n = 14), Streptococcus dysgalactiae 16.1% (n = 5), Streptococcus spp . 19.4% (n = 7) and others 13.9% (n = 5) . The loss of milk production was estimated at 300 kg milk for each cow injured by wasps and exhibiting clinical mastitis . An increase in the bulk-milk somatic cell count, from 186 x 103 at 1 month prior to the outbreak to a peak of 1200 x 10(3) in the post-outbreak month, was noted . The culling rate reached 13.6% (eight of 59) of the affected cows . In summary, the considerable economic losses caused by the wasp infestation resulted from decreased milk production and a decline in milk quality, culling of affected cows, and increased demand for use of drugs and veterinary care.

Biochemistry, 2002 Dec 24, 41(51), 15144 - 51
A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides; Choi YH et al.; In contrast to the conventional dogma that carbohydrates are poorly immunogenic T-cell-independent antigens, zwitterionic polysaccharides (ZPSs) can significantly stimulate T-cell proliferation and regulate abscess formation in bacterial infection . Despite their similar biological activities, ZPSs from various bacteria are greatly different in primary chemical compositions and building block linkages . To identify the common structural features that govern the peculiar immunologic activity of ZPSs, we have been determining three-dimensional structures of compositionally different ZPSs by NMR spectroscopy and molecular mechanics and dynamics calculations . We report here the conformation of type 1 capsular polysaccharide from the human pathogen Streptococcus pneumoniae (Sp1) to be a right-handed helix with repeated zwitterionically charged grooves . We also report the striking similarity between the structures of Sp1 and our previously determined PS A2 from Bacteroides fragilis . These results support our hypothesis that T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized by specific receptors and that account for their common property as T-cell activators.

Arch Otolaryngol Head Neck Surg, 2002 Dec, 128(12), 1361 - 4
Presentation, diagnosis, and management of deep-neck abscesses in infants; Cmejrek RC et al.; OBJECTIVE: To clarify the presenting signs and symptoms, clinical course, pathogenic organisms, and management of deep-neck-space abscesses in infants . DESIGN: Retrospective chart review . SETTING: Tertiary care academic children's hospital . PATIENTS: Records of 25 patients 9 months or younger with deep-neck-space abscesses from July 1989 through May 1999 were reviewed . MAIN OUTCOME MEASURE: Resolution of abscess . RESULTS: Presenting symptoms included neck mass, 92% (n = 23); fever, 60% (n = 15); and dysphagia and/or poor intake by mouth, 36% (n = 9) . Overall, patients were symptomatic for a mean duration of 3.8 days before presenting to the hospital; 21 of 22 evaluated patients had elevated white blood cell counts . Imaging included 68% computed tomographic scan (n = 17) and 44% plain radiographs (n = 11) . On the basis of radiology and operative findings, locations of the abscesses were as follows: anterior triangle, 8; parapharyngeal, 5; posterior triangle, retropharyngeal, and undefined, 3 each; submandibular, 2; and parotid, 1 . Of 17 scanned patients, 13 had some degree of airway compromise evident on computed tomography . All were treated with incision and drainage, 3 of 25 intraorally and 22 of 25 externally . Pus was identified in all 25; 20 of these grew Staphylococcus aureus, 1 grew group A Streptococcus, and 4 grew no organism . All patients received intravenous antibiotics for a mean of 4.8 days and oral antibiotics for a mean of 11 days . Only 1 patient required a second procedure . CONCLUSIONS: Deep-neck-space abscesses in infants are rapidly progressive, often cause airway compromise, and usually present with fever and neck mass . The most common pathogen is S aureus . Patients are effectively treated with incision and drainage coupled with intravenous followed by oral antibiotics.

Microbiology, 2002 Dec, 148(Pt 12), 3961 - 70
lcd from Streptococcus anginosus encodes a C-S lyase with alpha,beta-elimination activity that degrades L-cysteine; Yoshida Y et al.; Hydrogen sulfide is highly toxic to mammalian cells . It has also been postulated that hydrogen sulfide modifies haemoglobin resulting in haemolysis . The enzyme that produces hydrogen sulfide from L-cysteine was purified from Streptococcus anginosus . Using the N-terminal amino acid sequence of the purified enzyme, the lcd gene encoding L-cysteine desulfhydrase was cloned; the recombinant protein was then purified to examine its enzymic and biological characteristics . This L-cysteine desulfhydrase had the Michaelis-Menten kinetics K(m)=0.62 mM and V(max)=163 micro mol min(-1) mg(-1) . DL-Cystathionine, L-cystine, S-(2-aminoethyl)-L-cysteine, 3-chloro-DL-alanine and S-methyl-L-cysteine were substrates for the enzyme, whereas D-cysteine, DL-homocysteine, L-methionine, DL-serine, DL-alanine, L-cysteine methyl ester, L-tryptophan, L-tyrosine and L-phenylalanine were not . These findings suggest that this L-cysteine desulfhydrase is a C-S lyase that catalyses the alpha,beta-elimination (alphaC-N and betaC-S) reaction . In addition, it is demonstrated that the hydrogen sulfide produced by this enzyme caused the modification and release of haemoglobin in sheep erythrocytes.

Biochem Biophys Res Commun, 2003 Jan 3, 300(1), 149 - 54
The activation of glycolysis performed by the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase in the model system; Arutyunov DY et al.; Influence of non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) on glycolysis was investigated . The addition of GAPN-which oxidizes glyceraldehyde-3-phosphate directly to the 3-phosphoglyceric acid-led to the strong increase in the rate of lactate accumulation in the rat muscle extract with low ADP content . The lactate accumulation was also observed in the presence of GAPN in rat muscle extract, which contained only ATP and no ADP . This can be the evidence of the "futile cycle" stimulated by GAPN . Here ADP can be regenerated from ATP by the phosphoglycerate kinase reaction . The high resistance of GAPN from Streptococcus mutans towards inactivation by natural oxidant-H(2)O(2) was showed . This feature distinguishes GAPN from phosphorylating glyceraldehyde-3-phosphate dehydrogenase, which is very sensitive to modification by hydrogen peroxide . A possible role of the oxidants and non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase in the regulation of glycolysis is discussed.

FEMS Microbiol Lett, 2002 Dec 17, 217(2), 219 - 24
Screening of large numbers of Streptococcus pneumoniae isolates for mutations associated with fluoroquinolone resistance using an oligonucleotide probe assay; Davies TA et al.; Mutations at a relatively small number of sites in parC, parE and gyrA account for most of the fluoroquinolone resistance in Streptococcus pneumoniae clinical isolates . A high throughput oligonucleotide probe assay was developed to screen for mutations in the quinolone-resistance determining region (QRDR) of parC (Ser79), gyrA (Ser81) and parE (Asp435) of Streptococcus pneumoniae . Eight oligonucleotide probes (17mers) were used in the presence of tetramethyl ammonium chloride so that the melting temperature was dependent on length and not on base composition . Using this assay it was possible to accurately detect QRDR mutations from several hundred S . pneumoniae clinical isolates that were grown on nylon membranes .

Immunity, 2002 Dec, 17(6), 713 - 23
Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses; Haas KM et al.; The CD21/35 receptor provides an important link between innate and adaptive immunity . Its importance during protective immune responses to encapsulated extracellular bacteria was assessed using a new line of mice completely deficient in CD21/35 expression (CD21/35(-/-)) . CD21/35 expression was essential for the rapid trapping of C3dg-antigen complexes by B cells in vivo, especially in splenic marginal zones . Despite normal B cell development in CD21/35(-/-) mice, T cell-independent and -dependent antibody responses to low-dose antigens were significantly decreased, with a striking impairment in IgG3 responses . Accordingly, CD21/35(-/-) mice were more susceptible to acute lethal Streptococcus pneumoniae infection . Thus, CD21/35 expression is critical for early protective antibody responses to lethal pathogens that rapidly multiply and quickly overwhelm the immune system.

J Periodontol, 2002 Nov, 73(11), 1292 - 8
Bactericidal effect of the Er:YAG laser on dental implant surfaces: an in vitro study; Kreisler M et al.; BACKGROUND: The aim of the in vitro study was to examine the bactericidal effect of an Er:YAG laser on common dental implant surfaces . METHODS: Seventy-two titanium platelets with 3 different surfaces--sandblasted and acid-etched (SA), titanium plasma-sprayed (TPS), and hydroxyapatite-coated (HA)--were incubated with a suspension of Streptococcus sanguinis (ATCC 10556) . Irradiation at pulse energies of 60 and 120 mJ and a frequency of 10 pps was performed on a computer-controlled XY translation stage . After laser treatment the specimens were sonicated and the bacterial growth examined by counting colony forming units on blood agar plates . Temperature elevations during irradiation were investigated using K-type thermocouples . Laser treated implant surfaces were analyzed by means of electron microscopy . RESULTS: Compared to non-irradiated specimens, mean bacterial reductions of 99.51% (SA), 98.39% (HA), and 99.6% (TPS) at a pulse energy of 60 mJ and 99.92% (SA), 99.85% (HA), and 99.94% (TPS) at 120 mJ were calculated . At these laser parameters, no excessive temperature elevations or morphological implant surface alterations were detected . CONCLUSIONS: Even at low energy densities, the Er:YAG laser has a high bactericidal potential on common implant surfaces . Clinical studies are justified to evaluate the applicability and efficacy of the Er:YAG laser in the treatment of peri-implantitis.

Zhonghua Nan Ke Xue, 2002, 8(5), 329 - 31
{Practicability study on a group of vigilant chemical compounds including chlorheridine diacetate}; Fu XM et al.; OBJECTIVES: To test in vitro the spermatozocidine drug which can also prevent sex transmitting diseases (STD) pathogens . METHODS: Chlorheridine diacetate and other three chemical compounds were applied in vitro spermatozocidine and sperm inhibitting tests . RESULTS: The lowest concentrations of chlorheridine diacetate and p-nitrophenol which can inhibit human sperm in 20 seconds were 1.25 mg/ml . The minimal inhibitory concentration and minimal bactericidal concentration of chlorheridine diacetate and p-nitrophenol on Streptococcus albus Stemberg were 0.125 to 0.50 mg/ml and 0.25 to 1.00 mg/ml . CONCLUSIONS: Chlorheridine diacetate and p-uitrophenol have strong spermatozocidine and antibacteria effects.

Proc Natl Acad Sci U S A, 2002 Dec 24, 99(26), 16969 - 74 Epub 2002 Dec 11.
The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice; Brown JS et al.; The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae . The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response . Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens . However, the functional importance of the classical pathway for innate immunity to S . pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined . By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S . pneumoniae . Our results show that the proportion of a population of S . pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway . Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S . pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation . These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.

Mol Cell Probes, 2002 Oct, 16(5), 385 - 90
Real-time quantitative PCR for the detection of Streptococcus pneumoniae in the middle ear fluid of children with acute otitis media; Saukkoriipi A et al.; PCR based on the amplification of pneumolysin gene fragments has previously been applied to demonstrate Streptococcus pneumoniae in clinical specimens . Here, a real-time PCR method for the detection and quantification of pneumococci by amplifying a 206-bp fragment of the pneumolysin-encoding gene is described . The amplified fragments were detected simultaneously using fluorescent-labeled sequence-specific hybridization probes . The applicability of the assay to clinical samples was evaluated by studying 50 middle ear fluid (MEF) specimens from children with acute otitis media . Twenty-six of the MEF samples were positive by real-time PCR and the numbers of genome equivalents detected varied from 90 to 88,000/microl in 17 culture-positive samples and from 1 to 1,200/microl in 9 culture-negative samples . The results were compared to culture findings and to results obtained by using agarose gel electrophoresis or Europium-labeled hybridization probes for the detection of amplification products of conventional PCR . The sensitivity and specificity of the real-time PCR assay developed in the present study compared to culture were 100 and 73%, and to conventional PCR with agarose gel and/or TRF detection 93 and 96%, respectively . The real-time PCR assay was found to be rapid, easy to use, and sensitive in detecting and quantifying pneumococci.

Scand J Infect Dis, 2002, 34(10), 764 - 6
Streptococcus bovis bacteremia from a venous access port in a patient with AIDS; Angel-Moreno A et al.; We report the first case of S . bovis bacteremia related to endoluminal colonization of a venous access port in a setting of advanced HIV infection, neutropenia and co-infection with HBV . The patient had no bowel abnormalities . The clinical picture was mild and was resolved by removal of the device.

Scand J Infect Dis, 2002, 34(10), 720 - 8
Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia; San Pedro GS et al.; Intravenous (i.v.) to oral linezolid (600 mg twice daily for both, with optional aztreonam) and a cephalosporin regimen (i.v . ceftriaxone 1 g twice daily followed by oral cefpodoxime 200 mg twice daily) were compared for the treatment of community-acquired pneumonia (CAP), with emphasis on patients with Streptococcus pneumoniae . This multicenter, randomized, open-label trial was conducted in 27 countries in 6 continents . Efficacy was assessed 12-28 d following treatment . Clinical and laboratory safety assessments were evaluated; isolates for microbiologic assessments were identified primarily by sputum or blood culture . In all treated patients (linezolid, n = 381; ceftriaxone/cefpodoxime, n = 366), linezolid had a higher clinical cure rate than ceftriaxone/cefpodoxime (83.0% vs . 76.4%, respectively; p = 0.040) . S . pneumoniae was isolated in 73.2% (186/254) of patients at baseline, with similar eradication rates in the linezolid and ceftriaxone/cefpodoxime groups (88.7% vs . 89.9%, respectively; p = 0.830) . Linezolid had a superior clinical cure rate (93.1% vs . 68.2%; p = 0.021) in patients with S . pneumoniae bacteremia . Logistic regression analyses revealed that linezolid-treated patients with bacteremia, pleural effusion, cardiac comorbidities, diabetes or abnormal white blood cell counts had significantly better outcomes than cephalosporin-treated patients . Both regimens were well tolerated, although the incidence of drug-related adverse events was higher in the linezolid group than in the ceftriaxone/cefpodoxime group (21.3% vs . 11.2%, respectively; p = 0.0002) . In summary, empiric i.v./oral linezolid was more effective than ceftriaxone/cefpodoxime in patients hospitalized with CAP, with comparable cure rates in S . pneumoniae pneumonia and higher cure rates in pneumonia complicated by bacteremia.

Appl Opt, 2002 Dec 1, 41(34), 7334 - 8
Determination of bacterial activity by use of an evanescent-wave fiber-optic sensor; John MS et al.; A novel technique based on fiber-optic evanescent-wave spectroscopy is proposed for the detection of bacterial activity in human saliva . The sensor determines th e specific concentration of Streptococcus mutans in saliva, which is a major causative factor in dental caries . In this design, one prepares the fiber-optic bacterial sensor by replacing a portion of the cladding region of a multimode fiber with a dye-encapsulated xerogel, using the solgel technique . The exponential decay of the evanescent wave at the core-cladding interface of a multimode fiber is utilized for the determination of bacterial activity in saliva . The acidogenic profile of Streptococcus mutans is estimated by use of evanescent-waveabsorption spectra at various levels of bacterial activity.

Mikrobiyol Bul, 2002 Jan, 36(1), 23 - 9
{Retrospective microbiologic evaluation of vaginal cultures}; Acikgoz ZC et al.; Vaginal culture is one of the most difficult cultures to be evaluated in clinical microbiology practice . The necessity of some expensive and complicated processes for diagnosis of some specific agents, age related variability of normal vaginal flora and failure caused by temporary presence of some pathogens in normal flora can be listed among the probable causes of that problem . In this study 8050 vaginal cultures performed in our hospital laboratories between 1 March 1999-15 September 2001 were evaluated retrospectively . It was shown that the most frequently isolated pathogens were yeasts belonging to the Candida genus (26.8%) . The second most frequent pathogen (13.8%) was Gardnerella vaginalis which was an indicator of bacterial vaginosis . The rate of isolation of Trichomonas vaginalis was 2.2% . Group B streptococcus (GBS) was isolated in 2.0% of the total cultures . Some nonspecific bacteria, mainly Gram negative bacilli, were noted as colonizing agents (6.5%).

Harefuah, 2002 Nov, 141(11), 957 - 9, 1010
{The severity and prolonged morbidity of community acquired pneumonia caused by group A Streptococcus}; Aharoni S et al.; We describe a case report of a sixteen year old patient who was admitted with severe group A streptococcal (GAS) pleuro-pneumonia, underwent pleurocentesis and recovered after two weeks of hospitalization, although complete recovery lasted for another three weeks . The present publication aims to highlight the severe, prolonged and complicated course of GAS pneumonia in children which has not yet been reported in Israel . Accurate diagnosis is crucial for appropriate therapy, which is a prolonged i.v . course of penicillin.

Nippon Jinzo Gakkai Shi, 2002 Oct, 44(7), 558 - 63
{A case of fulminant acute poststreptococcal glomerulonephritis showing mesangiolysis and crescent formation preceded by erysipelas}; Hikita T et al.; A 66-year-old man with erysipelas was admitted with complaints of oliguria and massive proteinuria/hematuria . He was diagnosed as having acute poststreptococcal glomerulonephritis(APSGN) due to erysipelas infected by group A streptococcus pyogenes . On admission, his white cell count increased to 31,000, and CRP was 27.3 mg/dl . Serum urea nitrogen and creatinine were increased to 90.1 mg/dl and 4.5 mg/dl, respectively . He had diabetes mellitus(HbA1c 7.9%) and liver dysfunction(total bilirubin 3.5 mg/dl, AST 76 IU, ALT 41 IU) caused by alcoholic liver cirrhosis . Hypocomplementemia was found in addition to ASO 216 U/ml and ASK 10,240 x . After antibiotics treatment was initiated, inflammation of the erysipelas began to improve . Disseminated intravascular coagulation syndrome, probably due to sepsis, occurred on the 5th hospital day . He died of gastrointestinal bleeding on the 18th hospital day . Renal autopsy revealed 37% formation of fibrocellular crescents, and marked mesangiolysis was noted by light microscopy . Granular deposition of C3 and IgG was seen along the capillary walls on immunofluorescence study . Intramembranous deposits were scattered on electron microscopy . This case illustrates a fulminant type of APSGN, which was in part attributed to the presence of diabetes and alcoholic liver cirrhosis . Histological findings of crescent formation and marked mesangiolysis may account for the fulminant clinical course.

Chemotherapy, 2002 Dec, 48(5), 232 - 7
The activity of levofloxacin and comparator agents against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999 and 2000; Jones ME et al.; BACKGROUND: Increases in penicillin-resistant Streptococcus pneumoniae have been documented worldwide . METHODS: During 1999 and 2000, 5,015 S . pneumoniae isolates were collected from 13 countries on five continents and tested for antimicrobial susceptibility . RESULTS: Penicillin resistance rates were as follows: South Korea, 70.1%; Hong Kong, 50.3%; Thailand, 39.3%; France, 28.7%; Spain, 24.8%; Mexico, 18.1%; Ireland, 11.8%; South Africa, 11.1%; Italy, 9.4%; United Kingdom, 3.1%; Brazil, 2.9%; China, 2.3%, and Germany, 0.7% . Resistance to azithromycin, clarithromycin and trimethoprim-sulfamethoxazole was commonly associated with penicillin resistance . Levofloxacin-resistant isolates were detected in 8 of 13 countries: Germany (0.2%), France (0.4%), Thailand (0.5%), South Korea (0.9%), Mexico (1.5%), Spain (1.6%), China (3.3%) and Hong Kong (8.0%) . Multidrug resistance (resistance to >/=3 antimicrobial classes) occurred in 626/5,015 isolates (12.5%) . Levofloxacin was active against 96.0% (601/626) of the multidrug-resistant (MDR) isolates and 99.7% (4,374/4,389) of the non-MDR isolates . CONCLUSION: Although relatively high levels of levofloxacin resistance were detected in China and Hong Kong, overall, levofloxacin remained active against >99% of clinical isolates of S . pneumoniae despite their resistance to other agents . Continued surveillance of S . pneumoniae will track any changes in levofloxacin activity, should they occur .

Chest, 2002 Dec, 122(6), 2212 - 6
Evaluation of the polymerase chain reaction method for detection of Streptococcus pneumoniae DNA in pleural fluid samples; Falguera M et al.; STUDY OBJECTIVE: Streptococcus pneumoniae is the most frequent causative agent of community-acquired pneumonia (CAP); however, an etiologic diagnosis by traditional techniques can be accomplished in only a small percentage of patients with CAP . Pleural fluid is present in approximately 40% of patients with CAP; therefore, we hypothesized that detection of S pneumoniae DNA in pleural fluid by polymerase chain reaction (PCR) may help to increase the rate of diagnosis of pneumococcal pneumonia . DESIGN: A prospective study of cases . SETTING: A university hospital in Lleida, Spain . PATIENTS AND METHODS: One hundred two samples of pleural fluid (51 samples from consecutive adult patients with pneumonia and 51 samples from unselected control subjects) were tested by the nested-PCR method to detect selected pneumolysin gene of S pneumoniae, and the results were compared with those provided by alternative diagnostic methods . RESULTS: PCR in pleural fluid had a diagnostic sensitivity of 78% in patients with pneumococcal pneumonia, with positive results in 2 of 2 patients (100%) and 5 of 7 patients (71%) who had positive or negative pleural fluid culture findings, respectively . PCR results were also positive in 3 of 24 patients (12%) with pneumonia of unknown etiology and negative in all patients with pneumonia due to microorganisms other than S pneumoniae . Thus, the calculated specificity was 93% . Among control subjects, PCR gave positive results in two cases (4%) . CONCLUSION: The nested-PCR test, applied to pleural fluid samples from patients with CAP, showed a sensitivity of 78% and a specificity of 93% in the diagnosis of pneumococcal pneumonia.

J Biol Chem, 2003 Mar 14, 278(11), 9885 - 95 Epub 2002 Dec 08.
Zinc binding and dimerization of Streptococcus pyogenes pyrogenic exotoxin C are not essential for T-cell stimulation; Swietnicki W et al.; Streptococcal pyrogenic enterotoxin C (Spe-C) is a superantigen virulence factor produced by Streptococcus pyogenes that activates T-cells polyclonally . The biologically active form of Spe-C is thought to be a homodimer containing an essential zinc coordination site on each subunit, consisting of the residues His(167), His(201), and Asp(203) . Crystallographic data suggested that receptor specificity is dependent on contacts between the zinc coordination site of Spe-C and the beta-chain of the major histocompatibility complex type II (MHCII) molecule . Our results indicate that only a minor fraction of dimer is present at T-cell stimulatory concentrations of Spe-C following mutation of the unpaired side chain of cysteine at residue 27 to serine . Mutations of amino acid residues His(167), His(201), or Asp(203) had only minor effects on protein stability but resulted in greatly diminished MHCII binding, as measured by surface plasmon resonance with isolated receptor/ligand pairs and flow cytometry with MHCII-expressing cells . However, with the exception of the mutants D203A and D203N, mutation of the zinc-binding site of Spe-C did not significantly impact T-cell activation . The mutation Y76A, located in a polar pocket conserved among most superantigens, resulted in significant loss of T-cell stimulation, although no effect was observed on the overall binding to human MHCII molecules, perhaps because of the masking of this lower affinity interaction by the dominant zinc-dependent binding . To a lesser extent, mutations of side chains found in a second conserved MHCII alpha-chain-binding site consisting of a hydrophobic surface loop decreased T-cell stimulation . Our results demonstrate that dimerization and zinc coordination are not essential for biological activity of Spe-C and suggest the contribution of an alternative MHCII binding mode to T-cell activation.

J Autoimmun, 2002 Dec, 19(4), 233 - 40
Restriction in the usage of variable beta regions in T-cells infiltrating valvular tissue from rheumatic heart disease patients; Figueroa F et al.; Rheumatic Heart Disease (RHD) is a delayed consequence of a pharyngeal infection with group A streptococcus (GAS), usually ascribed to a cross-reactive immune response to the host's cardiac tissues . Several GAS proteins have been reported to be superantigens, also raising the possibility that T cells in RHD could be driven by superantigens . We therefore analysed the variable beta (V beta) repertoire of T cells infiltrating heart valves from chronic RHD patients undergoing elective valvular surgery . We analysed 15 valve specimens from patients with longstanding quiescent RHD and control valves from four non-rheumatic individuals . Total RNA was extracted from fresh valve tissue and employed to amplify 22 V beta genes by RT-PCR . In valvular tissue, a restricted number of only 2 to 9 V beta regions were detected as opposed to the findings in control valves . In 8 RHD valves, the expression of V beta1, 2, 3, 5.1, 7, 8, 9 or 14 was marked . These V beta regions have been related to GAS superantigens . Our results evidence the presence of a restricted set of T lymphocytes in valvular tissue from a majority of patients with chronic RHD and suggest that valvular sequelae in these patients might be related to a local antigen or superantigen driven inflammatory process that persists even many years after the initial triggering event.

Eur J Neurosci, 2002 Dec, 16(11), 2113 - 22
Interferon-gamma differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophages; Hausler KG et al.; During bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto- and chemokines . In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern . Here, we analyzed the capacity of interferon-gamma (IFNgamma) to serve as such a leucocyte-to-microglia signal . Production of cyto- and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram-negative Escherichia coli or cell walls from Gram-positive Streptococcus pneumoniae (PCW) . IFNgamma presence during the stimulation (0.1-100 ng/mL) modulated the patterns of LPS- and PCW-induced cyto- and chemokine release in a dose-dependent, potent and complex manner . While amounts of TNFalpha and IL-6 remained nearly unchanged, IFNgamma enhanced the production of IL-12, MCP-1 and RANTES, but attenuated that of KC, MIP-1alpha and MIP-2 . Release modulation was obtained with IFNgamma preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation . Together the changes observed for the microglial chemokine release under IFNgamma would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations--as actually seen during the course of bacterial meningitis . The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte-derived IFNgamma could potentially regulate the microglial chemokine release pattern.

Ann Thorac Cardiovasc Surg, 2002 Jun, 8(3), 177 - 9
Rupture of a smoldering mycotic aneurysm of the thoracic aorta into the lung; Shinonaga M et al.; A 65-year-old man was a diagnosed with meningitis and bacteremia, as Streptococcus pneumoniae was isolated from spinal fluid and blood cultures . After three weeks of antibiotic therapy, computed tomography revealed a ruptured aneurysm of the descending thoracic aorta . The aneurysm had appeared during the first episode of meningitis but had remained silent for two years . The patient underwent in situ Dacron graft replacement and his postoperative course was uneventful with no infectious complication.

Afr J Reprod Health, 2001 Aug, 5(2), 130 - 4
Storage beyond three hours at ambient temperature alters the biochemical and nutritional qualities of breast milk; Eteng MU et al.; The effect of storage on stability of human breast milk was investigated in 30 lactating mothers . Samples stored for 3, 6 and 24 hours at ambient temperature of 302K (29 degrees) were analysed for protein, lactose, pH, and microbial content . There were significant (p < 0.01) decreases in protein, lactose and pH upon storage for 6 and 24 hours, compared with storage for 3 hours as control . The mean +/- SEM values for protein for 6 and 24 hours were 15.56 +/- 0.48 and 13.27 +/- 0.50, compared with 17.26 +/- 0.41 for 3 hours . For lactose, corresponding values for 6 and 24 hours were 0.08 +/- 0.005 and 0.07 +/- 0.006, compared with 3 hours (0.09 +/- 0.005) . The pH values were 6.1 +/- 0.09, 5.9 +/- 0.07 in 3, 6 and 24 hour samples rspectively . The skin floras investigated were Streptococcus viridians, Straphylococcus aureus and Staphylococcus albus . The microbial content increased with increase in storage time from 3 to 24 hours . The predominant bacterial specie was S . Albus, followed by S.viridians and S . aureus . A positive correlation (r = 0.453, p < 0.01) between lactose level and pH were obtained . These results suggest that breast milk is stable for 3 hours, beyond which significant changes occur in its biochemical composition and nutritional quality . The implications of these findings are discussed with respect to its consequences on their child's survival.

Clin Infect Dis, 2002 Dec 15, 35(12), 1505 - 11 Epub 2002 Dec 04.
Widespread use of fluoroquinolones versus emerging resistance in pneumococci; Goldstein EJ et al.; During the past decade, respiratory-tract pathogens have shown an increase in resistance to all classes of antimicrobial agents . Although the increasing prevalence of penicillin-resistant Streptococcus pneumoniae has resulted in an increased reliance on newer classes of agents, such as the fluoroquinolones, the broad use of these agents has contributed to increasing prevalence of strains with in vitro fluoroquinolone resistance, which are associated with treatment failures, nosocomial outbreaks, and patient fatalities . Strategies to limit this emerging dilemma and preserve the clinical utility of these agents are needed.

Annu Rev Physiol, 2003, 65, 349 - 69 Epub 2002 May 01.
The gastric biology of Helicobacter pylori; Sachs G et al.; Helicobacter pylori is a neutralophilic, gram-negative, ureolytic organism that is able to colonize the human stomach but does not survive in a defined medium with a pH <4.0 unless urea is present . In order to live in the gastric environment, it has developed a repertoire of acid resistance mechanisms that can be classified into time-independent, acute, and chronic responses . Time-independent acid resistance depends on the structure of the organism's inner and outer membrane proteins that have a high isoelectric point, thereby reducing their proton permeability . Acute acid resistance depends on the constitutive synthesis of a neutral pH optimum urease that is an oligomeric Ni(2+)-containing heterodimer of UreA and UreB subunits . Gastric juice urea is able to rapidly access intrabacterial urease when the periplasmic pH falls below approximately 6.2 owing to pH-gating of a urea channel, UreI . This results in the formation of NH3, which then neutralizes the bacterial periplasm to provide a pH of approximately 6.2 and an inner membrane potential of -101 mV, giving a proton motive force of approximately -200 mV . UreI is a six-transmembrane segment protein, with homology to the amiS genes of the amidase gene cluster and to UreI of Helicobacter hepaticus and Streptococcus salivarius . Expression of these UreI proteins in Xenopus oocytes has shown that UreI of H . pylori and H . hepaticus can transport urea only at acidic pH, whereas that of S . salivarius is open at both neutral and acidic pH . Site-directed mutagenesis and chimeric analysis have identified amino acids implicated in maintaining the closed state of the channel at neutral pH and other amino acids that play a structural role in channel function . Deletion of ureI abolishes the ability of the organism to survive in acid and also to colonize the mouse or gerbil stomach . However, if acid secretion is inhibited in gerbils, the deletion mutants do colonize but are eradicated when acid secretion is allowed to return, showing that UreI is essential for gastric survival and that the habitat of H . pylori at the gastric surface must fall to pH 3.5 or below . The chronic response is from increased Ni(2+) insertion into the apo-enzyme, which results in a threefold increase in urease, which is also dependent on expression of UreI . This allows the organism to live in either gastric fundus or gastric antrum depending on the level of acidity at the gastric surface . There are other effects of acid on transcript stability that may alter levels of protein synthesis in acid . Incubation of the organism at acidic pH also results in regulation of expression of a variety of genes, such as some outer membrane proteins, that constitutes an acid tolerance response . Understanding of these acid resistance and tolerance responses should provide novel eradication therapies for this carcinogenic gastric pathogen.

Am J Ophthalmol, 2002 Dec, 134(6), 908 - 10
Postoperative infection with group A beta-hemolytic Streptococcus after blepharoplasty; Goldberg RA et al.; PURPOSE: To report a case of group A beta-hemolytic streptococcal infection with signs of early necrotizing fasciitis after cosmetic blepharoplasty in a healthy patient . DESIGN: Interventional case report . METHODS: A healthy 59-year-old woman underwent outpatient bilateral upper and lower blepharoplasty with midface lifting . Thirty hours postoperatively she developed marked pain and edema of the left eyelids and face, and a violaceous eyelid bulla, which heralded early necrotizing fasciitis . Culture of the serosanguinous exudates from the left eyelid revealed group A beta-hemolytic Streptococcus organisms . RESULTS: The patient was treated with intravenous antibiotics, intravenous corticosteroids, hyperbaric oxygen therapy, and wound debridement . The infection resolved with mild cicatrization of the left upper eyelid . CONCLUSIONS: Group A beta-hemolytic Streptococcus is an increasingly recognized cause of infection that occurs after trauma or surgery, even in highly vascularized areas such as the eyelids and face . It is a potentially devastating infection, particularly in vascularly compromised patients, and requires immediate and aggressive treatment.

An Esp Pediatr, 2002 Nov, 57(5), 408 - 13
{Bacteremic pneumococcal pneumonia}; Pineda Solas V et al.; BACKGROUND: Streptococcus pneumonia is the most common bacterial cause of community-acquired pneumonia in children . The reference standard for etiological diagnosis is isolation of S . pneumoniae from blood Since the advent of conjugate vaccines, disease caused by this organism can now be prevented . Many studies have been performed of the global incidence of invasive pneumococcal infections and of pneumococcal meningitis but few studies investigated bacteremic pneumococcal pneumonia and its complications in children . OBJECTIVES: To determine the incidence, patient characteristics, clinical signs, laboratory data, percentage and days of hospitalization, response to antibiotic treatment, antibiotic resistance, complications and causal serogroups of bacteremic pneumococcal pneumonia in our environment in order to estimate requirements for systematic vaccination programs . MATERIAL AND METHODS: From January 1990 to May 2001, data on all pediatric cases of invasive pneumococcal infections diagnosed in our hospital were collected . Several characteristics of patients with bacteremic pneumococcal pneumonia were analyzed . Bacteremic pneumococcal pneumonia was diagnosed in patients with positive blood or pleural fluid cultures for S . pneumoniae and radiographically evident pulmonary infiltrate . The incidence of both types of pneumonia were determined according to population census data . All S . pneumonia strains were sent to the Pneumococci Reference Laboratory of the Instituto Carlos III in Madrid for serotyping . We estimated the serotype coverage of the pneumococcal 7-valent conjugate vaccine according to the serotypes included in this vaccine and their distribution . RESULTS: Forty cases of bacteremic pneumococcal pneumonia were diagnosed, yielding an incidence of 17,10 and 5 cases per 10(5) children aged less than 2, 4 and 15 years old respectively . The mean age was 50 months and 43% were aged less than 4 years . Peaks occurred in January, March, April and May . A total of 77.5% of the patients were admitted to hospital and the mean length of stay was 9.2 days . The mean duration of fever was 2 days and was 4.2 days in patients with pleural empyema . All patients presented fever and its mean duration before admission was 4 days . Fifty-eight percent of the patients had cough . Thirty-nine percent appeared generally unwell, vomiting was present in 47% and abdominal pain in 28% . Respiratory auscultation detected rales in 30% of the patients, hypophonesis in 28% and polypnea or dyspnea in 35% . Most patients showed alveolar bilateral infiltrations and 20% had pleural empyema . Seventy-eight percent had WBC counts > 15,000 and 93% showed neutrophilia of > 60% . Erythrocyte sedimentation rate and C-reactive protein were elevated in 77% and 85% of the patients, respectively . Overall, 40% of the isolates showed intermediate susceptibility to penicillin and 5% were resistant . Eighteen percent showed intermediate susceptibility to cefotaxime and 18% were resistant to erythromycin . Thirty-four strains were resistant to erythromycin . Thirty-four strains were serogroups and in children < or = 59 months, 34% of the serogroups were included in the pneumococcal 7-valent pneumococcal conjugate vaccine . CONCLUSION: The significant morbidity of bacteremic pneumococcal pneumonia and the implicated serogroups supports the use of the new heptavalent vaccine in the pediatric age group.

An Esp Pediatr, 2002 Nov, 57(5), 401 - 7
{Epidemiology of invasive pneumococcal disease in children in Gipuzkoa (Spain) from 1981 to 2001}; Iglesias Sanchez L et al.; OBJECTIVES: To assess the epidemiological characteristics of invasive pneumococcal disease (IPD) in children in Gipuzkoa (Spain) as well as the serotype distribution among these episodes and to analyze the potential impact of new conjugate vaccines . METHODS: We performed a retrospective study of cases of IPD in the pediatric population (< 15 years) between 1981 and 2001 . Patients were included if blood, cerebrospinal, joint or peritoneal fluid isolates were culture-positive for Streptococcus pneumoniae . RESULTS: One hundred twenty-nine episodes (30 meningitis, 39 bacteremic pneumonia, 7 peritonitis, 1 arthritis and 52 bacteremia without focus) were identified . The incidence of IPD in children increased throughout the study period and from 1999-2001 was 12.6 cases per 100,000/ year in children aged < 15 years, 34.5 in those < 5 years, 48.4 in those < 2 years and 40.8 in infants < 2 months . The incidence of pneumococcal meningitis was similar throughout the study period (1981-2001): 1.3 in children aged < 15 years, 3.5 in those < 5 years, 8.1 in those < 2 years and 10.2 in infants < 2 months . From 1989 to 2001 mortality was 1 % (1/98 cases) . The pneumococcal serotypes and serogroups present in the 7-valent vaccine accounted for 60.5 % and 70.9 % of the cases (9-valent vaccine: 70.2 % and 80.6 %; 11-valent vaccine: 76.6 % and 87.2 %) . From 1999-2001, penicillin resistance was 35.4 % and erythromycin resistance was 38.7 % . CONCLUSIONS: The incidence of IPD in children in Gipuzkoa has increased in the last few years, with rates similar to those in other European countries . Continued surveillance is required to assess the impact of the new conjugate vaccines on this infection.

J Org Chem, 2002 Dec 13, 67(25), 8789 - 93
Synthesis of novel nocathiacin-class antibiotics . Condensation of glycolaldehyde with primary amides and tandem reductive amination of amadori-rearranged 2-oxoethyl intermediates; Hrnciar P et al.; Nocathiacin I (1) and nocathiacin IV (2) are novel indole-containing thiazolyl peptide antibiotics, which exhibit potent activity against key Gram-positive bacterial pathogens, including multi drug-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium . New nocathiacins 7-12 were prepared from 2 by a condensation with glycolaldehyde followed by tandem reductive amination of the 2-oxoethyl intermediate 4 . The latter was formed via Amadori rearrangement from initial 2-hydroxyethylideneamide 3 . This transformation readily tolerates the complex architecture of nocathiacins and allows selective incorporation of water solubilizing groups to the primary amide in 2 without protecting group manipulation.

Am J Pathol, 2002 Dec, 161(6), 2219 - 28
CD44 deficiency leads to enhanced neutrophil migration and lung injury in Escherichia coli pneumonia in mice; Wang Q et al.; CD44 is a major cell-surface receptor for hyaluronic acid (HA), a glycosaminoglycan component of extracellular matrix . HA-CD44 interactions have been implicated in leukocyte extravasation into an inflammatory site . This study examined the role of CD44 in acute inflammatory responses during pneumonias induced by Escherichia coli and Streptococcus pneumoniae using CD44-deficient mice . In E . coli-induced pneumonia, neutrophil accumulation in the lungs and edema formation was increased by 84% and 88%, respectively, in CD44-deficient mice compared to wild-type mice . In contrast, no difference was observed between these genotypes in S . pneumoniae-induced pneumonia, and the HA content in the lungs decreased after instillation of S . pneumoniae, but not E . coli, in both genotypes . Studies to determine the mechanisms for this enhanced response showed that: 1) neutrophil apoptosis was not different between these two genotypes in either type of pneumonia; 2) CD44 deficiency resulted in enhanced mRNA expression of several inflammatory genes; and 3) CD44-deficient neutrophils migrated through Matrigel in response to chemoattractants faster and in greater numbers than wild-type neutrophils in vitro and this increase was in part dependent on HA content in the Matrigel . These data demonstrate that CD44 deficiency results in enhanced inflammation in E . coli but not S . pneumoniae-induced pneumonia, suggesting a previously unrecognized role for CD44 in limiting the inflammatory response to E . coli.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2002 Dec, 94(6), 746 - 55
Identification of bacteria in acute endodontic infections and their antimicrobial susceptibility; Khemaleelakul S et al.; OBJECTIVE: The purpose of the study was to identify the bacterial composition of the microbiota from acute endodontic abscesses/cellulitis and their antimicrobial susceptibilities . STUDY DESIGN: Purulence from 17 patients with acute endodontic abscesses/cellulitis was obtained by needle aspiration and processed under anaerobic conditions . Bacteria were isolated and identified by biochemical or molecular methods . The antimicrobial susceptibility of isolated bacteria was determined by using the Etest . RESULTS: All 17 aspirates contained a mix of microorganisms . A total of 127 strains of bacteria were isolated . Of 127 strains, 80 strains were anaerobes and 47 strains were aerobes . The mean number of strains per sample was 7.5 (range, 3 to 13) . The average number of viable bacteria was 6.37 x 10(7) (range, 10(4) to 10(8)) colony-forming units/mL . Strict anaerobes and microaerophiles were the dominant bacteria in 82% (14 of 17) of the cases . The genera of bacteria most frequently encountered were Prevotella and Streptococcus . Prevotella and Peptostreptococcus were frequently found to dominate the mixture . The combination of Prevotella and Streptococcus was found in 53% (9 of 17) . The previously reported uncultured Prevotella clone PUS9.180 was frequently identified . The percentage of bacteria susceptible/intermediate for each antibiotic in this study was penicillin V, 81% (95 of 118); metronidazole, 88% (51 of 58); amoxicillin, 85% (100 of 118); amoxicillin + clavulanic acid, 100% (118 of 118); and clindamycin, 89% (105 of 118) . CONCLUSIONS: The present results confirm the existence of mixed infection with the predominance of anaerobic bacteria in acute endodontic abscesses/cellulitis . The frequency of uncultured Prevotella clone PUS9.180 suggests the possible key role of this Prevotella species in acute endodontic infections . Penicillin V still possesses antimicrobial activity against the majority of bacteria isolated from acute endodontic infections . However, if penicillin V therapy has failed to be effective, the combination of penicillin V with metronidazole or amoxicillin with clavulanic acid is recommended . Switching to clindamycin is another good alternative.

Acta Paediatr, 2002, 91(11), 1265 - 7
Acute rheumatic fever associated with Henoch-Schönlein purpura: report of three cases and review of the literature; Eisenstein EM et al.; AIM: To describe a possible relationship between Henoch-Schonlein purpura and rheumatic fever . METHODS: Patients with features of both diseases were identified by reviewing the hospital records . Medline and reference lists from published articles were used to search for previous reports of the two conditions occuring simultaneously . RESULTS: Three newly described cases, and three previous reports of Henoch-Schonlein purpura associated with rheumatic carditis or chorea were identified . CONCLUSIONS: The coexistence of these two disorders in some patients supports the view that Group A streptococcus may have a pathogenic role in Henoch-Schonlein purpura.

Acta Paediatr, 2002, 91(11), 1251 - 6
Epidemiology of invasive Streptococcus pneumoniae infections in children in an area of Barcelona, Spain; Pineda V et al.; AIM: Streptococcus pneumoniae is the most common cause of bacteraemia, pneumonia, sinusitis and acute otitis media . With the advent of conjugate vaccines, there is now the possibility of preventing disease caused by this organism . However, little is known about the epidemiology of invasive pneumococcal disease in children in Spain . The aim of this study was to determine the incidence and the clinical and microbiologic characteristics of invasive pneumococcal disease in Sabadell, an industrial area in the province of Barcelona, Spain . METHODS: From January 1990 to December 2000, the case records of children with pneumococcal invasive disease at Sabadell Hospital were retrospectively (1990-1996) reviewed and prospectively (1997-2000) collected . The hospital serves a population of 61,143 children under 15 y of age, 18,073 children under 4 y of age and 7300 children under 2 y of age . RESULTS: A total of 112 children (54% under 24 mo of age and 93% under 6 y of age) with invasive pneumococcal disease were diagnosed during a period of 11 y . The incidence of invasive pneumococcal disease was 76 per 100,000 for children aged 0 to 24 mo, 45 for children aged 0-48 mo and 16.6 for children aged 0-14 y . Occult bacteraemia was the most common manifestation of invasive pneumococcal disease (66 cases), pneumonia was the second form (34 cases) and meningitis (10 cases) and arthritis (2 cases) were the other clinical manifestations . Of the 105 strains tested, 8.6% were highly penicillin resistant, 37.1% were intermediately penicillin resistant . 16.2% were intermediately cefotaxime resistant and 32.4% were erythromycin resistant . Pneumococci of serogroups 6, 14, 18, 19, 1, 5, 4, 9, 23 and 33 were the most frequently isolated groups (92%) but only 6, 9, 14, 19 and 23 were resistant to penicillin, cefotaxime, or erythromycin . CONCLUSIONS: In this study the incidence of invasive pneumococcal disease was found to be greater than that reported elsewhere in Spain and Europe . Penicillin resistance levels are high but the trend towards increasing penicillin resistance may have ended over the past few years . The currently licensed seven-valent (7-V) pneumococcal conjugate vaccine would cover 78% of cases of invasive pneumococcal in children aged 0-14 y, 80% in children aged 0-24 mo and 100% of cases of penicillin- or cefotaxime-resistant invasive pneumococcal disease.

Curr Drug Targets Infect Disord, 2002 Mar, 2(1), 51 - 65
Non-fluorinated quinolones (NFQs): new antibacterials with unique properties against quinolone-resistant gram-positive pathogens; Roychoudhury S et al.; Wide variations in the antibacterial potency and spectrum of quinolones are presumably attributable, in part, to their variable potency against the molecular targets, DNA gyrase and topoisomerase i.v . In addition, susceptibility of quinolones to resistance development via known point mutations in the target genes gyrA and parC/grlA varies depending on the effective affinities of the compounds toward the mutated targets . Using a medicinal chemistry approach, a series of 8-methoxy, Non-Fluorinated Quinolones (NFQs), with fluorine in the R6 position of the traditional fluoroquinolones replaced with hydrogen, were designed to retain potency against DNA gyrase and/or topoisomerase i.v . with point mutations in the serine-aspartate/glutamate hotspots . This resulted in compounds with antibacterial activity against a broad-spectrum of bacterial species, including multidrug-resistant gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) . The efficacy of the NFQs was also demonstrated in a murine septicemia model . Furthermore, the design of the NFQs resulted in lower acute intravenous (i.v.) toxicity and clastogenicity relative to their 6-fluorinated counterparts . Use of the non-fluorinated quinolone nucleus allowed exploration of new structure-activity space and generation of a series of NFQs with unique combinations of affinities toward the wild type and mutated forms of the molecular targets.

J Antimicrob Chemother, 2002 Dec, 50(6), 953 - 64
Comparability of antimicrobial susceptibility test results from 22 European countries and Israel: an external quality assurance exercise of the European Antimicrobial Resistance Surveillance System (EARSS) in collaboration with the United Kingdom National External Quality Assurance Scheme (UK NEQAS); Bronzwaer S et al.; The goal of this exercise was to organize external quality assurance (QA) of antibiotic susceptibility testing for laboratories participating in EARSS and to assess the comparability of susceptibility test results across countries, and guidelines . In September 2000, UK NEQAS distributed a set of three Streptococcus pneumoniae strains, two Staphylococcus aureus strains and one Streptococcus haemolyticus strain . Laboratories reported the guideline followed, the interpretation of the susceptibility test result and the MIC, if tested . In this study we considered results 'concordant' if the reported interpretation of the participating laboratory agreed with the designated interpretation of reference laboratories . Overall, 433 (92%) of 471 laboratories from 23 countries reported back . Of the 8685 tests that were assessed, 8322 (96%) were interpreted correctly by the participants . Concordance for detection of penicillin non-susceptibility in the three S . pneumoniae strains was 96%, 90% and 87%, respectively . Laboratories performed extremely well in detecting oxacillin resistance in the homogeneously methicillin-resistant S . aureus (MRSA) strain, but the concordance rate dropped from 100% to 77% in the heterogeneously resistant MRSA strain . Concordance for detection of teicoplanin resistance in the S . haemolyticus strain was 82% . We stratified concordance rates first for country and then for guideline used, but observed only minor differences among countries and guidelines . Quantitative methods yielding an MIC were more concordant than non-MIC methods for penicillin resistance in the S . pneumoniae strains (94% versus 79%) . The NCCLS guideline was the most frequently followed, by 61% of laboratories from 19 countries . This exercise shows that, overall, countries participating in EARSS are capable of delivering susceptibility data of good quality . The comparability of susceptibility data for penicillin resistance in S . pneumoniae and for homogeneous methicillin resistance in S . aureus is satisfactory among European countries and across guidelines . However, we emphasize the importance of determining an MIC for suspected penicillin non-susceptible S . pneumoniae and for suspected glycopeptide non-susceptible S . aureus . Laboratories, particularly in some countries, may need to improve their capability to detect oxacillin resistance in heterogeneously resistant MRSA . For continuous external quality assessment we recommend that laboratories participate in national and international schemes with frequent distribution of control strains.

J Antimicrob Chemother, 2002 Dec, 50(6), 907 - 13
Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes; Hamilton-Miller JM et al.; OBJECTIVES: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketolide, against sensitive and erythromycin-resistant pneumococci; (ii) to subdivide erythromycin-resistant pneumococci into resistance phenotypes, more extensive than the conventional M and MLS(B) groups, by assessing susceptibilities to, and interactions between, erythromycin (14-membered macrolide), clindamycin (lincosamide), rokitamycin (16-membered macrolide), ABT-773 (ketolide), quinupristin (streptogramin B) and dalfopristin (streptogramin A) . METHODS: MICs and MBCs of ABT-773 were determined for 165 strains of pneumococci (113 resistant to erythromycin) . Extended phenotypes for the erythromycin-resistant strains were described in terms of intrinsic susceptibility to, and induction of resistance by, the antibiotics listed above . RESULTS: Erythromycin-resistant strains could be divided into 10 extended phenotypes (designated II-XI), two of which (II and IX) predominated . ABT-773 at 0.12 mg/L inhibited 109 strains (median 0.03 mg/L) . MICs for the other four strains (of phenotypes X and XI) were 0.25-1 mg/L . MICs were only slighter higher when measured on agar in CO(2) than by the NCCLS method (in broth in air) . MBCs were usually < or = 2 x MIC, but for 10 strains (eight of phenotype X, one each of types IX and XI) MBCs were > 1 mg/L, and three of the latter (all type X) were tolerant . Clones of reduced susceptibility (MICs 1-8 mg/L, increased by up to 32-fold) could be isolated from some strains of phenotypes VII, IX and X, but not from those of type II (efflux mechanism) or from erythromycin-sensitive strains . CONCLUSIONS: ABT-773 was active against all 113 erythromycin-resistant pneumococci tested, which belonged to 10 phenotypes . Extended phenotyping of pneumococci revealed interesting and potentially useful subdivisions of the classical phenotypes.

FEBS Lett, 2002 Dec 4, 532(1-2), 159 - 63
A novel mechanism for glucose side-chain formation in rhamnose-glucose polysaccharide synthesis; Ozaki K et al.; We have cloned two genes (rgpH and rgpI) that encode proteins for the formation of the glucose side-chains of the Streptococcus mutans rhamnose-glucose polysaccharide (RGP), which consists of a rhamnan backbone with glucose side-chains . The roles of rgpH and rgpI were evaluated in a rhamnan-synthesizing Escherichia coli . An E . coli strain that harbored rgpH reacted with antiserum directed against complete RGP, whereas the E . coli strain that carried rgpI did not react with this antiserum . Although E . coli:rgpH reacted strongly with rhamnan-specific antiserum, co-transformation of this strain with rgpI increased the number of glucose side-chains and decreased immunoreactivity with the rhamnan-specific antiserum significantly . These results suggest that two genes are involved in side-chain formation during S . mutans RGP synthesis in E . coli: one gene encodes a glucosyltransferase, and the other gene probably controls the frequency of branching . This is the first report to identify a gene that is involved in regulation of branching frequency in polysaccharide synthesis.

Int J Antimicrob Agents, 2002 Dec, 20(6), 412 - 8
Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000; Diekema DJ et al.; We report age-related trends in pathogen frequency and antimicrobial susceptibility from 25,745 bloodstream infections (BSI) due to bacterial pathogens reported from medical centres participating in the North American SENTRY Antimicrobial Surveillance Program between January 1997 and September 2000 . Staphylococcus aureus, Escherichia coli and coagulase-negative staphylococci (CoNS) were the most common pathogens, together accounting for 55% of all BSI pathogens during this time period . Among nosocomial BSI, CoNS were the most frequently isolated pathogens in infants less than 1 year of age, but S . aureus increased in frequency with increasing age . Among community-onset BSI pathogens, Streptococcus pneumoniae was the most frequently reported pathogen causing BSI in patients aged 1-5, S . aureus among those aged 6-64, and E . coli predominated at the extremes of age (less than 1 year and > or = 65 years of age) . Among key organism: antimicrobial agent combinations evaluated, oxacillin resistance in S . aureus increased with increasing age; conversely, oxacillin resistance among CoNS was highest among children 5 years of age or younger . Penicillin resistance among S . pneumoniae BSI was highest in children younger than 5 years, while vancomycin resistance among Enterococcus spp . predominated among nosocomial BSI in patients over 50 years of age . Important age-related differences exist in species distribution and antimicrobial susceptibility of pathogens causing BSI . This information should be helpful for clinicians as they consider empirical antimicrobial therapy for patients with suspected BSI across the age continuum .

Front Biosci, 2003 Jan 01, 8, s1 - 18
Molecular epidemiology of Streptococcus agalactiae (group B Streptococcus); Manning SD; Group B Streptococcus (GBS) is a common cause of sepsis and meningitis in newborns, and causes disease in pregnant women and non-pregnant adults . The incidence of disease among non-pregnant adults, particularly those with underlying conditions, is increasing . In addition, many individuals are asymptomatically colonized with GBS . When compared to group A Streptococcus and Streptococcus pneumoniae, however, little is known about the pathogenesis, natural history and transmission dynamics of GBS . Various molecular tools have been utilized to study this organism, including both phenotypic techniques, such as serotyping and multilocus enzyme electrophoresis, and genotypic techniques such as plasmid analysis and pulsed-field gel electrophoresis . This review outlines the contributions of these methods to our current understanding of GBS infections.

Front Biosci, 2003 Jan 01, 8, e87 - 93
Molecular epidemiology of Streptococcus pneumoniae mediated otitis media; McCoy S et al.; Streptococcus pneumoniae is leading cause of bacterial otitis media in young children . Increasing rates of antibiotic resistance and the changing epidemiology of pneumococcal strains dictate the need to develop new methods to study, control, and prevent these important infections . Investigation into the molecular epidemiology of these bacteria will provide important insights into disease; progress in this field is described below.

J Gynecol Obstet Biol Reprod (Paris), 2002 Nov, 31(7 Suppl), 5S74 - 83
{Management of threatening preterm labor with intact membranes: indications for antibiotics}; Winer N; OBJECTIVE: To analyse the benefits and disadvantages of systematic antibiotic therapy in patient presenting a preterm labor with intact membranes . METHODS: We reviewed French and English reports on Medline using to the following key words: "antibiotic therapy and preterm labor, preterm labor, streptococcus B, vaginose, mycoplasma, antenatal infection" . RESULTS: The systematic prescription of antibiotics is not recommended for patients presenting preterm labor who have intact membranes and no symptoms of infection . The benefit of antibiotics is small and shows a tendency to prolong the pregnancy and the reduction of maternal infection . No benefit has been shown for neonatal results . When early-onset neonatal sepsis develops in a case in which antepartum chemoprophylaxis was used, the isolated bacteria will present an increasing risk of bacterial drug resistance . Local treatment (cream or pessary) do not belong in the treatment of threatening preterm labor and are not recommended for the prevention of prematurity or materno fetal infection . Risk groups of patients who present a positive vaginal colonization are subject to discussion . Studies do not allow us to ascertain that antibiotics have a beneficial effect on prematurity in these groups . Antibiotics are recommended for the treatment of asymptomatic bacteriuria . This treatment reduces prematurity and maternal infections . Despite poor consensus criteria, if threatening preterm labor is associated with a bacteriuria, experts usually recommend treatment.

J Gynecol Obstet Biol Reprod (Paris), 2002 Nov, 31(7 Suppl), 5S43 - 51
{Prognostic and therapeutic value of biologic signs of infection in the management of preterm labor (amniocentesis excepted)}; Subtil D; During threatened preterm delivery, both general and local signs of infection increase the risks of amniotic infection, premature rupture of membranes, preterm delivery, and neonatal and/or maternal morbidity of infectious origin . Nonetheless, as antibiotics have not been sufficiently studied to be proved of benefit in chorioamnionitis with intact membranes, search for these general (C Reactive Protein, hyperleucocytosis) or cervical/vaginal (Group B Streptococcus, Escherichia Coli, bacterial vaginosis) signs of infection have not been proved to be really necessary . We have to except Group B Streptococcus, which have to be searched during weeks that precede delivery: in those cases where it is shown to be present in the cervix or the vagina, antibiotics must be prescribed during delivery (ANAES recommendation) . Finally, it must be emphasized that these recommendations are mainly based on the absence of studies specifically done to prove the benefits or risks of antenatal antibiotics - or fetal extraction - in case of chorioamnionitis with intact membranes . Systematic vaginal and blood samples (CRP, leukocytes, vaginal micro-organisms) would be helpful in determining the appropriate option in those situations.

J Clin Microbiol, 2002 Dec, 40(12), 4466 - 71
M types of group a streptococcal isolates submitted to the National Centre for Streptococcus (Canada) from 1993 to 1999; Tyrrell GJ et al.; The National Centre for Streptococcus (NCS) (Canada) determined the group A streptococcal (GAS) M types of 4,760 Canadian isolates submitted between 1993 and 1999 by classic serotyping . The 10 most frequently identified M types were M1 (26.4%), M12 (9.8%), M28 (8.9%), M3 (6.8%), M4 (6.2%), M11 (4.8%), M89 (3.1%), M6 (3.0%), M2 (2.6%), and M77 (1.9%) . Nontypeable isolates accounted for 15.4% of the collection . The province of Ontario submitted 51.1% of the isolates, followed by Quebec (21.2%) and Alberta (13.9%) . Together, these three provinces constituted 71.3% of the Canadian population in 1996 . The numbers of M types M1, M12, M28, and M3 occurred most frequently in subjects whose ages were <1 to 15 years and 25 to 45 years, as well as in the elderly (60 to 90 years) . Further analysis found that the four most frequently identified M types from blood, brain, and cerebrospinal fluid were M1 (28.2%), M28 (9.2%), M12 (9.1%), and M3 (8.2%), with 13.4% of isolates being nontypeable . The four isolates from throats most frequently identified were M1 (19.5%), M12 (15.3%), M3 (8.6%), and M28 (5%) with 19.4% of isolates being nontypeable . The sic gene of a subset of M1 strains (9.5% of the M1 collection) was sequenced . Of 36 sic types identified, the four most common were sic1.01 (22.8%), sic1.02 (14.9%), sic1.135 (10.5%), and sic1.178 (9.6%) . Together these four sic types further characterized nearly 60% of the M1 strains sequenced . In summary, from the years 1993 to 1999, the NCS detected 54 M types, of which 10 different M types constituted 73.5% of the collection . M1 was the most common GAS M type circulating in the Canadian population, responsible for more than a quarter of the isolates typed . The most common throat isolates differed in M-type and proportion from those of invasive isolates . Sequencing the sic gene further characterized the most common M-type serotype 1 in a fashion that may be useful for epidemiologic investigations.

Clin Exp Immunol, 2002 Dec, 130(3), 467 - 74
Inflammatory cytokine (interleukin 6 and tumour necrosis factor alpha) release in a human whole blood system in response to Streptococcus pneumoniae serotype 14 and its capsular polysaccharide; Jagger MP et al.; Gram-positive bacteria, which lack lipopolysaccharide (LPS), produce a septic-shock-like condition, accompanied by release of pro-inflammatory cytokines . Various components of the bacteria may be responsible for this . We stimulated a whole blood system with heat-inactivated Streptococcus pneumoniae serotype 14 (S14) bacteria, with pneumococcal S14 capsular polysaccharide (PPS S14) and with PPS S14 coated on to latex beads, to compare interleukin 6 (IL-6) and tumour necrosis factor alpha (TNFalpha) production over a six hour period, to ascertain the contribution of PPS to the inflammatory response . This was compared with the response to LPS . After sonication of the bacteria, their PPS content was estimated by an enzyme-linked immunoabsorbent assay, to compare this with the concentration of free PPS needed to generate cytokine release . The whole bacteria elicited a much larger cytokine response than the equivalent amount of PPS alone, whereas the PPS-coated beads gave minimal response . The different cytokine responses to PPS and LPS suggest that there are differences in the receptors and/or signalling pathways for Gram-negative and Gram-positive bacteria . We conclude that the estimated amount of PPS in the bacteria is not enough to account for the large cytokine response we observed . Since PPS could not be shown to contribute significantly to cytokine induction, specific antibodies to PPS would not play any significant role in combating cytokine release associated with pneumococcal infection and possible septic shock . This needs to be considered in production of future vaccines.

J Gynecol Obstet Biol Reprod (Paris), 2002 Oct, 31(6 Suppl), 4S65 - 4S73
{Obstetrical management of Streptococcus agalactiae}; Quentin R et al.; S . agalactiae is the main cause of maternal and neonatal infections . Correct bacteriological explorations of pregnant women and neonates with risk factors may allow early and effective antibiotherapy . The screening of S . agalactiae vaginal carriage at 34-38 weeks of amenorrhea and the administration of penicillin at delivery is considered as the best strategy for preventing S . agalactiae infections for asymptomatic patients.

Am Fam Physician, 2002 Nov 1, 66(9), 1685 - 92
Common issues in the care of sick neonates; Hashim MJ et al.; Newborn infants may be transferred to a special care nursery because of conditions such as prematurity (gestation less than 37 weeks), prolonged resuscitation, respiratory distress, cyanosis, and jaundice, and for evaluation of neonatal sepsis . Newborn infants' core temperature should be kept above 36.4 degrees C (97.5 degrees F) . Nutritional requirements are usually 100 to 120 kcal per kg per day to achieve an average weight gain of 150 to 200 g (5 to 7 oz) per week . Standard infant formulas containing 20 kcal per mL and maternal breast milk may be inadequate for premature infants, who require special formulas or fortifiers that provide a higher calorie content (up to 24 kcal per mL) . Intravenous fluids should be given when infants are not being fed enterally, such as those with tachypnea greater than 60 breaths per minute . Hypoglycemia can be asymptomatic in large-for-gestational-age infants and infants of mothers who have diabetes . A hyperoxia test can be used to differentiate between pulmonary and cardiac causes of hypoxemia . The potential for neonatal sepsis increases with the presence of risk factors such as prolonged rupture of membranes and maternal colonization with group B streptococcus . Jaundice, especially on the first day of life, should be evaluated and treated . If the infant does not progressively improve in the special care nursery, transfer to a tertiary care unit may be necessary.

J Vet Med B Infect Dis Vet Public Health, 2002 Oct, 49(8), 366 - 70
Aetiology and histopathology of bovine mastitis of espontaneous occurrence; Benites NR et al.; Infectious bovine mastitis is responsible for serious economic losses in dairy cattle breeding . Information about the damages caused by micro-organisms is of great interest and importance . The purpose of the present study was to report on the microbiological and histopathological aspects of the mammary parenchymas of slaughtered dairy cows . A total of 184 mammary glands were examined and samples of mammary parenchyma were collected for microbiological and histopathological examinations . Micro-organisms were isolated from 69.6% samples; 23 (12.5%) of the 184 samples did not show histological changes; inflammatory response was observed in 56 (30.4%) samples; inflammatory response and repair were present in 82 (44.6%) samples; repair process was verified in 23 (12.5%) of the mammary glands . Coagulase-negative Staphylococci were observed in 53.8% of the samples followed by coagulase-positive Staphylococci (7.6%), Prototheca sp . (2.2%) and Streptococcus dysgalactiae (1.6%) . Coagulase-negative Staphylococci and coagulase-positive Staphylococci were associated mainly to chronic inflammatory response and chronic inflammatory response and repair . Samples from which no micro-organisms were isolated (n = 56) had no histological changes in 82.6% of the cases . These results were higher (P < 0.05) when compared to the samples with micro-organisms and without histological changes (17.4%).

J Infect Dis, 2002 Dec 1, 186(11), 1608 - 14 Epub 2002 Nov 01.
Spread of Streptococcus pneumoniae and antibiotic-resistant S . pneumoniae from day-care center attendees to their younger siblings; Givon-Lavi N et al.; A prospective study was conducted to determine the association between pneumococcal carriage among 36 infants and young toddlers cared for at home and carriage among their older siblings who attended 8 day-care centers (DCCs); 71 pneumococcal strains acquired by the younger siblings were compared with those present in the DCCs for 6 months . In 76% of cases, > or =1 strain identical by serotype and antibiogram was isolated in the older siblings' DCC versus 32%-63% in all other DCCs (P<.001) . When phenotypically identical strains were compared by pulsed-field gel electrophoresis, the similarity between strains from older siblings' DCCs and the younger siblings' isolates was striking . This was not found when isolates from other DCCs were compared . Vaccinating DCC attendees with a 7-valent pneumococcal conjugate vaccine may play a key role in controlling the spread of antibiotic-resistant pneumococci, because the most resistant serotypes are included in the vaccine.

J Biol Chem, 2003 Jan 31, 278(5), 3079 - 88 Epub 2002 Nov 21.
The function of hydrophobic residues in the catalytic cleft of Streptococcus pneumoniae hyaluronate lyase . Kinetic characterization of mutant enzyme forms; Nukui M et al.; Streptococcus pneumoniae hyaluronate lyase is a surface antigen of this Gram-positive human bacterial pathogen . The primary function of this enzyme is the degradation of hyaluronan, which is a major component of the extracellular matrix of the tissues of vertebrates and of some bacteria . The enzyme degrades its substrate through a beta-elimination process called proton acceptance and donation . The inherent part of this degradation is a processive mode of action of the enzyme degrading hyaluronan into unsaturated disaccharide hyaluronic acid blocks from the reducing to the nonreducing end of the polymer following the initial random endolytic binding to the substrate . The final degradation product is the unsaturated disaccharide hyaluronic acid . The residues of the enzyme that are involved in various aspects of such degradation were identified based on the three-dimensional structures of the native enzyme and its complexes with hyaluronan substrates of various lengths . The catalytic residues were identified to be Asn(349), His(399), and Tyr(408) . The residues responsible for the release of the product of the reaction were identified as Glu(388), Asp(398), and Thr(400), and they were termed negative patch . The hydrophobic residues Trp(291), Trp(292), and Phe(343) were found to be responsible for the precise positioning of the substrate for enzyme catalysis and named hydrophobic patch . The comparison of the specific activities and kinetic properties of the wild type and the mutant enzymes involving the hydrophobic patch residues W292A, F343V, W291A/W292A, W292A/F343V, and W291A/W292A/F343V allowed for the characterization of every mutant and for the correlation of the activity and kinetic properties of the enzyme with its structure as well as the mechanism of catalysis.

J Bacteriol, 2002 Dec, 184(24), 6987 - 7000
Vancomycin tolerance induced by erythromycin but not by loss of vncRS, vex3, or pep27 function in Streptococcus pneumoniae; Robertson GT et al.; Vancomycin-tolerant Streptococcus pneumoniae is a growing problem among drug-resistant human pathogens . Some vancomycin-tolerant pneumococci have been reported to carry mutations in loci encoding a two-component regulatory system designated VncRS or in a proximal ABC transporter, Vex . A model was advanced proposing that the tolerance phenotype resulted from the inability of a vncS mutant to respond to the Vex-transported Pep27 "death peptide" signal and dephosphorylate VncR, thereby preventing relief of repression of autolytic and other cell death functions in response to antibiotics . To explore this hypothesis, we constructed mutations in vncS, vncR, vex3, and pep27 in S . pneumoniae strain R6 and two additional genetic backgrounds . The lytic responses of the isogenic DeltavncS, Deltavex3, DeltavncR, and Deltapep27 mutants, but not a DeltalytA strain, to vancomycin were indistinguishable from that of the parent strain . DeltavncS strains also failed to exhibit tolerance to vancomycin at various doses in multiple media and showed wild-type sensitivity to other classes of autolysis-inducing antibiotics . In contrast, addition of subinhibitory levels of the antibiotic erythromycin led to tolerance to vancomycin during late, but not early, exponential-phase growth in a DeltavncS strain, in the parent strain R6, and in two other strains bearing erythromycin resistance markers, namely, a DeltavncR strain and an unrelated DeltacomD strain that is defective in competence-quorum sensing . Thus, this tolerance effect resulted from changes in cell growth or other erythromycin-dependent phenomena and not inactivation of vncS per se . Consistent with these results, and in contrast to a previous report, we found that a synthetic form of Pep27 did not elicit lytic or nonlytic killing of pneumococci . Finally, microarray transcriptional analysis and beta-galactosidase reporter assays revealed VncS-dependent regulation of the vex123 gene cluster but did not support a role for VncRS in the regulation of autolytic or other putative cell death loci . Based on these findings, we propose that vancomycin tolerance in S . pneumoniae does not result from loss of vncS function alone.

FEMS Microbiol Lett, 2002 Nov 19, 217(1), 51 - 5
The effect of bovicin HC5, a bacteriocin from Streptococcus bovis HC5, on ruminal methane production in vitro; Lee SS et al.; Methane represents a loss of feed energy to ruminant animals, and nutritionists have sought methods of inhibiting ruminal methane production . When mixed ruminal bacteria (approximately 400 mg protein ml(-1)) from a cow fed timothy hay were incubated in vitro with carbon dioxide and hydrogen (0.5 atm) for less than 8 h, the first-order rate of methane production was 17 micromol ml(-1) . Semi-purified bacteriocin from Streptococcus bovis HC5 (bovicin HC5) inhibited methane production, by as much as 50%, and even a low concentration of bovicin HC5 (128 activity units (AU) ml(-1)) caused a significant decrease . Mixed ruminal bacteria that were transferred successively retained their ability to produce methane from carbon dioxide and hydrogen, and the first-order rate of methane production did not decrease . Cultures that were treated with bovicin HC5 (128 AU ml(-1)) gradually lost their ability to produce methane, and methane was not detected after four transfers . These latter results indicated that ruminal methanogens could not adapt and become resistant to bovicin HC5 . When the chromosomal DNA was amplified with 16S rDNA primers specific to archaea, digested with restriction enzymes (HhaI and HaeIII) and separated on agarose gels, approximately 12 fragments were observed . DNA from control and treated cultures (third transfer) had the same fragment pattern indicating bovicin HC5 was not selective . Given the perception that the routine use of antibiotics in animal feeds should be avoided, bacteriocins may provide an alternative strategy for decreasing ruminal methane production.

FEMS Microbiol Lett, 2002 Nov 19, 217(1), 23 - 30
Real-time PCR for quantification of Streptococcus mutans; Yano A et al.; A real-time polymerase chain reaction (PCR) assay was developed for the quantification of Streptococcus mutans . Primers targeting gtf genes of S . mutans were designed and tested for their specificity using 28 oral streptococcal strains, three other bacterial strains, and human DNA . The primers could amplify specifically the target DNA fragment from a mixture of oral streptococcus genomic DNA containing about 10 fg to 10 ng of S . mutans genome DNA . The real-time PCR produced a linear quantitative detection range over concentrations spanning seven exponential values, with a detection limit of a few copies of S . mutans' genomic DNA per reaction tube . The results of the real-time PCR assay corresponded well to those of conventional culture assays for S . mutans in saliva samples . A real-time PCR assay for Streptococcus sobrinus and Streptococcus downei was also established and produced results that corresponded well to those from conventional culture assays for S . sobrinus in saliva samples . These assays will be useful as a new means to assess one of the important risk factors for caries.

Clin Microbiol Infect, 2002 Nov, 8(11), 745 - 8
Susceptibility of strains of Streptococcus agalactiae to macrolides and lincosamides, phenotype patterns and resistance genes; Aracil B et al.; The Group B streptococcus (Streptococcus agalactiae) is a pathogen of increasing importance in human disease . We therefore studied the susceptibility of clinical isolates of S . agalactiae to penicillin G, erythromycin, azithromycin and clindamycin using National Committee for Clinical Laboratory Standards methodology, and we also determined the phenotypes of macrolide-lincosamide susceptibility and the resistance genes implicated in a group of selected isolates of the different phenotypes . We used 221 isolates collected between 1997 and 1999 in two Health Authority Areas in Mostoles and Granada, Spain . The minimal concentration for 90% inhibition (MIC90) for penicillin G was 0.12 mg/L and all the isolates tested were susceptible . One hundred and eighty-five (83.7%) were susceptible to erythromycin and azithromycin and 191 (86.4%) were susceptible to miocamycin and clindamycin . Twenty-three isolates (10.4%) had a constitutive MLSB phenotype, seven (3.2%) an inducible phenotype, and six (2.7%) an M phenotype . All except one of the MLSB phenotype isolates tested (n = 23) carried erm genes; in two strains with the mef (A) gene, all the M phenotype (n = 6) isolates tested carried mef genes, while erm and mef (A) genes were absent in all the macrolide-lincosamide-susceptible (n = 12) isolates tested . In our environment, resistance to macrolide and lincosamide in S . agalactiae was present in 10-16% of the isolates . The majority of resistant strains had the MLSB phenotype.

J Immunol, 2002 Dec 1, 169(11), 6149 - 53
Zwitterionic polysaccharides stimulate T cells by MHC class II-dependent interactions; Kalka-Moll WM et al.; Polysaccharides of pathogenic extracellular bacteria commonly have negatively charged groups or no charged groups at all . These molecules have been considered classic T cell-independent Ags that do not elicit cell-mediated immune responses in mice . However, bacterial polysaccharides with a zwitterionic charge motif (ZPSs), such as the capsular polysaccharides of many strains of Bacteroides fragilis, Staphylococcus aureus, and Streptococcus pneumoniae type 1 elicit potent CD4(+) T cell responses in vivo and in vitro . The cell-mediated response to ZPS depends on the presence of both positively charged and negatively charged groups on each repeating unit of the polysaccharide . In this study, we define some of the requirements for the presentation of ZPS to CD4(+) T cells . We provide evidence that direct interactions of T cells with APCs are essential for T cell activation by ZPS . Monocytes, dendritic cells, and B cells are all able to serve as APCs for ZPS-mediated T cell activation . APCs lacking MHC class II molecules do not support this activity . Furthermore, mAb to HLA-DR specifically blocks ZPS-mediated T cell activation, while mAbs to other MHC class II and class I molecules do not . Immunoprecipitation of lysates of MHC class II-expressing cells following incubation with ZPS shows binding of ZPS and HLA-DR . Electron microscopy reveals colocalization of ZPS with HLA-DR on the cell surface and in compartments of the endocytic pathway . These results indicate that MHC class II molecules expressing HLA-DR on professional APCs are required for ZPS-induced T cell activation . The implication is that binding of ZPS to HLA-DR may be required for T cell activation.

Am J Perinatol, 2002 Oct, 19(7), 367 - 78
Delivery room risk factors for meconium aspiration syndrome; Liu WF et al.; The objective of this study is to identify risk factors for meconium aspiration syndrome (MAS) in newborns born through meconium-stained amniotic fluid (MSAF) . From May 27, 1994 to June 9, 1997 maternal and neonatal data were prospectively collected on all infants born through MSAF . Development of MAS was the primary outcome . Using bivariate and logistic regression analysis we identified risk factors for MAS . There were 8,967 births during this period: 7.9% (708 of 8,967) were delivered through MSAF . Respiratory symptoms developed in 6.8% (48 of 708) of births . Of these, 50% (24 of 48) were excluded due to the diagnosis of transient tachypnea of the newborn (17), respiratory distress syndrome (4), group B streptococcus pneumonia (1), congenital cytomegalic inclusion disease (1), and supraventricular tachycardia (1) . Of the 24 infants with respiratory symptoms consistent with MAS, 45.8% (11 of 24) required ventilatory support, one required extracorporeal-membrane oxygenation . Bivariate analysis identified six risk factors ( p <0.05): Apgar <7 at 1 minute, Apgar <7 at 5 minutes, thick meconium, fetal distress, suction of infant's stomach by delivery room team at <5 minutes of age, and need for resuscitation . Tracheal meconium was very prevalent in our population at 74% of all intubated infants, and was not significantly associated with MAS . Logistic regression analysis identified four independent risk factors . Looking at multiple prediction models, an infant with fetal distress, Apgar <7 at 1 and 5 minutes and thick meconium has a 79.8% probability of developing respiratory symptoms . If these risk factors are not present, there is a 0.8% risk . In our cohort, this group had 16.7% positive predictive value (4 of 24) and 99.6% negative predictive value (657 of 660) . In meconium deliveries, infants with thick meconium, fetal distress, and Apgar scores <7 at 1 and 5 minutes are at high risk for development of respiratory symptoms . Infants delivered in the absence of all of these risk factors are at low risk for development of MAS.

Pediatr Infect Dis J, 2002 Nov, 21(11), 1008 - 16
Multinational study of pneumococcal serotypes causing acute otitis media in children; Hausdorff WP et al.; BACKGROUND: Streptococcus pneumoniae is a major cause of acute otitis media (AOM) in young children . More than 90 immunologically distinct pneumococcal serotypes have been identified, but limited information is available regarding their relative importance in AOM . METHODS: We analyzed nine existing datasets comprising pneumococcal isolates from middle ear fluid samples collected from 1994 through 2000 from 3,232 children with AOM from Finland, France, Greece, Israel, several East European countries, the US and Argentina . We examined the distribution of pneumococcal serotypes in relation to several demographic and epidemiologic variables, including gender, age, antibiotic resistance and source of culture material . RESULTS: The major serotypes identified included 19F and 23F, each comprising 13 to 25% of pneumococcal middle ear fluid isolates in most datasets; 14 and 6B, comprising 6 to 18%; whereas 6A, 19A and 9V each comprised 5 to 10% . Despite differences in location, study design and antibiotic susceptibility, each major serotype was prominent in most age groups of each dataset . Serotypes represented in the 7-valent pneumococcal conjugate vaccine (PCV-7, 4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 60 to 70% of all pneumococcal isolates in the 6- to 59-month age range, but only 40 to 50% of isolates in children <6 or >/=60 months old . Serotype 3 and, in certain datasets, serotypes 1 and 5, were more important in the <6- and >/=60-month age groups . In each age group vaccine-related serotypes (mainly 6A and 19A) comprised an additional 10 to 15% of all pneumococcal isolates . Four serotypes (23F, 19F, 14 and 6B) accounted for 83% of all penicillin-resistant observations . CONCLUSIONS: This analysis of several geographically diverse datasets indicates that a limited number of serotypes, largely represented in PCV-7, accounted for the majority of episodes of pneumococcal AOM in children between 6 and 59 months of age . Certain serotypes appeared to be relatively more significant in children <6 months or >59 months of age.

Retina, 2002 Oct, 22(5), 622 - 32
Contribution of pneumolysin and autolysin to the pathogenesis of experimental pneumococcal endophthalmitis; Ng EW et al.; PURPOSE: To determine the contribution of pneumolysin and autolysin, two putative pneumococcal virulence proteins, to the pathogenesis of Streptococcus pneumoniae endophthalmitis . METHODS: Endophthalmitis was established in Lewis rats by intravitreal injection of pneumococcal strains at an inoculum of 10 organisms . The virulence of three closely related type 2 S . pneumoniae strains were compared: a pneumolysin-deficient derivative (PLN-A), an autolysin-deficient derivative (AL-6), and their isogenic wild-type parent (D 39) . Clinical and histologic inflammation scores were compared 24 hours and 48 hours after inoculation . RESULTS: Eyes infected with PLN-A and AL-6 strains showed less anterior segment inflammation clinically at 24 hours than did eyes infected with the wild-type strain . Histologic examination at 24 hours showed significantly less corneal infiltration and vitritis and more relative preservation of retinal tissue in eyes infected with PLN-A and AL-6 strains than in eyes infected with the wild-type strain . At 48 hours, no observable differences between PLN-A and wild-type strains were present clinically or histologically . Histologically, however, the AL-6 strain caused less retinal damage than did the wild-type strain . CONCLUSIONS: Intraocular infection with pneumolysin-deficient S . pneumoniae results in less severe tissue damage in the first 24 hours of disease compared with infection with pneumolysin-producing S . pneumoniae . Autolysin-deficient S . pneumoniae shows a similar degree of attenuated virulence . Pneumolysin and autolysin may contribute to the early pathogenesis of pneumococcal endophthalmitis.

Biochem Soc Trans, 2002 Nov, 30(Pt 6), 1050 - 5
Mechanistic diversity and regulation of Type II fatty acid synthesis; Marrakchi H et al.; Fatty acid biosynthesis is catalysed in most bacteria by a group of highly conserved proteins known as the Type II fatty acid synthase (FAS) system . The Type II system organization is distinct from its mammalian counterpart and offers several unique sites for selective inhibition by antibacterial agents . There has been remarkable progress in the understanding of the genetics, biochemistry and regulation of Type II FASs . One important advance is the discovery of the interaction between the fatty acid degradation regulator, FadR, and the fatty acid biosynthesis regulator, FabR, in the transcriptional control of unsaturated fatty acid synthesis in Escherichia coli . The availability of genomic sequences and high-resolution protein crystal structures has expanded our understanding of Type II FASs beyond the E . coli model system to a number of pathogens . The molecular diversity among the pathway enzymes is illustrated by the discovery of a new type of enoyl-reductase in Streptococcus pneumoniae {enoyl-acyl carrier protein (ACP) reductase II, FabK}, the presence of two enoyl-reductases in Bacillus subtilis (enoyl-ACP reductases I and III, FabI and FabL), and the use of a new mechanism for unsaturated fatty acid formation in S . pneumoniae ( trans -2- cis -3-enoyl-ACP isomerase, FabM) . The solution structure of ACP from Mycobacterium tuberculosis revealed features common to all ACPs, but its extended C-terminal domain may reflect a specific interaction with very-long-chain intermediates.

Ann Thorac Surg, 2002 Nov, 74(5), S1781 - 5; discussion S1792-9
Replacing the ascending aorta and aortic valve for acute prosthetic valve endocarditis: is using prosthetic material contraindicated?
Hagl C, Galla JD, Lansman SL, Fink D, Bodian CA, Spielvogel D, Griepp RB.
BACKGROUND: The use of prosthetic material (rather than a homograft) for ascending aorta/aortic valve replacement (Bentall procedure) in cases of acute prosthetic valve endocarditis is controversial . We report favorable results using this technique almost exclusively (a homograft was used in only 3 patients with hematological problems) during a 12-year interval . METHODS: Twenty-eight patients (55 +/- 14 years; 22 male) underwent a Bentall procedure for acute prosthetic valve endocarditis between 1988 and 2000 . Twenty-five patients had undergone previous aortic valve replacement (1 with concomitant mitral valve replacement, 4 with coronary artery bypass grafting), and 3 had had a previous Bentall operation . The median interval between initial surgery and reoperation was 13 months (range, 1 to 106) . Sixty-eight percent of operations were urgent or emergencies . Ninety-three percent of patients had significant aortic regurgitation; complete annuloaortic dehiscence occurred in 71%, and in 57%, an abscess was found . Causative organisms were identified in 25 of 28 patients: Staphylococcus epidermidis (9), Staphylococcus aureus (7), Streptococcus viridans (6), Pseudomonas (2), and Legionella (1) . RESULTS: Twenty-three patients had mechanical and 5 had biological valves implanted during the Bentall procedure . Hypothermic circulatory arrest was used in 64% . Hospital mortality was 11%: there was one intraoperative death, and two before discharge (one cardiac, one sepsis) . Eighty-nine percent survived without stroke . During follow-up (median, 44.5 months; complete in 92%), 1 patient died of recurrent endocarditis at 4 months . CONCLUSIONS: These results indicate that prosthetic root replacement may be superior to use of a homograft for acute aortic prosthetic valve endocarditis, with only a 4% incidence of recurrent endocarditis and reoperation.

Clin Infect Dis, 2002 Dec 1, 35(11), 1353 - 9 Epub 2002 Nov 11.
An outbreak of group A Streptococcal infection among health care workers; Kakis A et al.; We describe the nosocomial transmission of group A Streptococcus species (GAS) from a single source patient to 24 health care workers (HCWs) . DNA typing revealed that all of the isolates were identical to that of the source patient . The isolates were M type 1, positive for production of nicotine adenine dinucleotidase, and negative for opacity factor, all of which are factors reported to have a higher correlation with invasive disease . The 24 HCWs developed symptoms of pharyngitis < or =4 days after exposure to the source patient . Nosocomial transmission occurred < or =25 h after exposure to the source patient, before the institution of outbreak-control measures . A questionnaire was distributed to HCWs to help identify the factors responsible for the high attack rate among those who were exposed . Invasive GAS disease in a nosocomial setting can be highly transmissible . Rapid identification, early treatment, and adherence to infection-control practices may prevent or control outbreaks of infection.

Clin Infect Dis, 2002 Dec 1, 35(11), 1345 - 52 Epub 2002 Nov 13.
Characteristics of Streptococcus pneumoniae and atypical bacterial infections in children 2-5 years of age with community-acquired pneumonia; Esposito S et al.; The characteristics of community-acquired pneumonia associated with Streptococcus pneumoniae infection were compared with those associated with atypical bacterial infection and with mixed S . pneumoniae-atypical bacterial infection in 196 children aged 2-5 years . S . pneumoniae infections were diagnosed in 48 patients (24.5%); atypical bacterial infections, in 46 (23.5%); and mixed infections, in 16 (8.2%) . Although white blood cell counts and C-reactive protein levels were higher in patients with pneumococcal infections, no other clinical, laboratory, or radiographic characteristic was significantly correlated with the different etiologic diagnoses . There was no significant difference in the efficacy of the different treatment regimens followed by children with S . pneumoniae infection, whereas clinical failure occurred significantly more frequently among children with atypical bacterial or mixed infection who were not treated with a macrolide . This study shows the major role of both S . pneumoniae and atypical bacteria in the development of community-acquired pneumonia in young children, the limited role of clinical, laboratory, and radiological features in predicting etiology, and the importance of the use of adequate antimicrobial agents for treatment.

Zentralbl Gynakol, 2002 Jul, 124(7), 378 - 85
{Three case reports of breast abscess after nipple piercing: underestimated health problems of a fashion phenomenon}; Jacobs VR et al.; OBJECTIVE: Piercing is a growing fashion trend among young people . Nipple piercing has shown an increase over the last years . We report about three coincidental cases of breast abscess after nipple piercing within the last months in our clinics and discuss the related problems for health and society . MATERIAL AND METHODS: Retrospective analysis of three case reports regarding course of illness and reasons as well as review of literature and internet . RESULTS: Three patients average age 31.9 (28-35) years were hospitalized with breast abscess after nipple piercing (2 x left, 1 x right) . The distance piercing to infection was on average 7.7 (5-12) months . In all patients the abscess was incised and the abscess cavity removed, two had an irrigation tubing for a three days, all received i . v . antibiotics postoperatively . Evidence for bacteria was found in case 1: PCR-confirmation of atypical mycobacteria and coagulase negative staphylococcus, case 2: coagulase negative staphylococcus and group B-streptococcus and case 3: green and microaerophilic staphylococcus . The length of hospital stay was on average 8.0 (6-9) days/case, the hospital costs were 3 624,54 e (3 000,26-4 310,58 e) euro;/case . In a follow-up period of 10,0 (5-15) months one relapse occurred which had to be re-operated . CONCLUSION: Nipple piercing has grown in popularity within the last years and is in general not a stigma of a subculture or lower social classes any more . However, the risk for breast infection is on the one hand underestimated by the women and on the other hand played down by piercing studios . Breast infection after nipple piercing is rarely documented in scientific literature and data bases . Only seven case reports are scientifically published so far . Healing of the wound channel varies and can take up to 6-12 months . The risk for infection is approximately 10-20 %, often in a interval of months after the procedure . Insufficient understanding as well as inconsequent performance of hygienic preparation of the wound beneath other risk factors like nicotine abuse, wrongs size of jewelry, post breast enlargement with prosthesis etc . increase the risk of breast infection after nipple piercing . Due to obvious under documentation this is the largest series of breast infection after nipple piercing in the world.

Infect Immun, 2002 Dec, 70(12), 7176 - 8
Peptidoglycan N-acetylglucosamine deacetylase, a putative virulence factor in Streptococcus pneumoniae; Vollmer W et al.; Many glucosamine residues of the pneumococcal peptidoglycan (PG) are not acetylated, which makes the PG resistant to lysozyme . A capsular type III mutant with an inactivated pgdA gene (encoding the peptidoglycan N-acetylglucosamine deacetylase A) became hypersensitive to exogenous lysozyme and showed reduced virulence in the intraperitoneal mouse model.

Infect Immun, 2002 Dec, 70(12), 7095 - 104
Characterization of two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks; Smoot LM et al.; The pathogenesis of acute rheumatic fever (ARF) is poorly understood . We identified two contiguous bacteriophage genes, designated speL and speM, encoding novel inferred superantigens in the genome sequence of an ARF strain of serotype M18 group A streptococcus (GAS) . speL and speM were located at the same genomic site in 33 serotype M18 isolates, and no nucleotide sequence diversity was observed in the 33 strains analyzed . Furthermore, the genes were absent in 13 non-M18 strains tested . These data indicate a recent acquisition event by a distinct clone of serotype M18 GAS . speL and speM were transcribed in vitro and upregulated in the exponential phase of growth . Purified SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes and human peripheral blood mononuclear cells in picogram amounts . SpeL preferentially expanded human T cells expressing T-cell receptors Vbeta1, Vbeta5.1, and Vbeta23, and SpeM had specificity for Vbeta1 and Vbeta23 subsets, indicating that both proteins had superantigen activity . SpeL was lethal in two animal models of streptococcal toxic shock, and SpeM was lethal in one model . Serologic studies indicated that ARF patients were exposed to serotype M18 GAS, SpeL, and SpeM . The data demonstrate that SpeL and SpeM are pyrogenic toxin superantigens and suggest that they may participate in the host-pathogen interactions in some ARF patients.

Infect Immun, 2002 Dec, 70(12), 6880 - 90
Opsonophagocytosis-inhibiting mac protein of group a streptococcus: identification and characteristics of two genetic complexes; Lei B et al.; Recently, it was reported that a streptococcal Mac protein (designated Mac(5005)) made by serotype M1 group A Streptococcus (GAS) is a homologue of human CD11b that inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear leukocytes (PMNs) (B . Lei, F . R . DeLeo, N . P . Hoe, M . R . Graham, S . M . Mackie, R . L . Cole, M . Liu, H . R . Hill, D . E . Low, M . J . Federle, J . R . Scott, and J . M . Musser, Nat . Med . 7:1298-1305, 2001) . To study mac variation and expression of the Mac protein, the gene in 67 GAS strains representing 36 distinct M protein serotypes was sequenced . Two distinct genetic complexes were identified, and they were designated complex I and complex II . Mac variants in each of the two complexes were closely related, but complex I and complex II variants differed on average at 50.66 +/- 5.8 amino acid residues, most of which were located in the middle one-third of the protein . Complex I Mac variants have greater homology with CD11b than complex II variants . GAS strains belonging to serotypes M1 and M3, the most abundant M protein serotypes responsible for human infections in many case series, have complex I Mac variants . The mac gene was cloned from representative strains assigned to complexes I and II, and the Mac proteins were purified to apparent homogeneity . Both Mac variants had immunoglobulin G (IgG)-endopeptidase activity . In contrast to Mac(5005) (complex I), Mac(8345) (complex II) underwent autooxidation of its cysteine residues, resulting in the loss of IgG-endopeptidase activity . A Mac(5005) Cys94Ala site-specific mutant protein was unable to cleave IgG but retained the ability to inhibit IgG-mediated phagocytosis by human PMNs . Thus, the IgG-endopeptidase activity was not essential for the key biological function of Mac(5005) . Although Mac(5005) and Mac(8345) each have an Arg-Gly-Asp (RGD) motif, the proteins differed in their interactions with human integrins alpha(v)beta(3) and alpha(IIb)beta(3) . Binding of Mac(5005) to integrins alpha(v)beta(3) and alpha(IIb)beta(3) was mediated primarily by the RGD motif in Mac(5005), whereas binding of Mac(8345) involved the RGD motif and a region in the middle one-third of the molecule whose sequence is different in Mac(8345) and Mac(5005) . Taken together, the data add to the emerging theme in GAS pathogenesis that allelic variation in virulence genes contributes to fundamental differences in host-pathogen interactions among strains.

Infect Immun, 2002 Dec, 70(12), 6779 - 87
Enhanced immunogenicity of a genetic chimeric protein consisting of two virulence antigens of Streptococcus mutans and protection against infection; Zhang P et al.; The saliva-binding region (SBR) of the cell surface antigen I/II (AgI/II) and the glucan-binding region (GLU) of the glucosyltransferase enzyme of Streptococcus mutans have been implicated in the initial adherence of S . mutans to saliva-coated tooth surfaces and the subsequent sucrose-dependent accumulation of S . mutans, respectively . Here, we describe the construction and characterization of a genetic chimeric protein consisting of the two virulence determinants SBR and GLU (SBR-GLU) . The effectiveness of this construct in inducing mucosal and systemic immune responses to each virulence determinant following intranasal immunization was compared to that of each antigen alone or an equal mixture of SBR and GLU (SBR+GLU) in a mouse model . Furthermore, the ability of antibodies induced to SBR-GLU to protect against S . mutans infection was also investigated . Immunization of mice with the chimeric protein SBR-GLU resulted in significantly enhanced (P < 0.001) levels of serum immunoglobulin G (IgG) anti-SBR antibody activity compared to those in the SBR and SBR+GLU groups . The SBR-GLU-immunized mice also demonstrated a significant (P < 0.05) increase in salivary and vaginal IgA antibody responses to SBR and GLU . Analysis of the serum IgG subclass responses to SBR in mice immunized with SBR alone indicated a mixed IgG1 and IgG2a response . A preferential IgG1 response compared to an IgG2a anti-GLU response was induced in mice immunized with GLU alone . Similarly, a preferential IgG1 response was also induced to SBR when GLU was present in either a mixed or conjugated form . Finally, a significant reduction (P < 0.05) in S . mutans colonization was observed only in mice immunized with the SBR-GLU chimeric protein . Taken together, our results indicate that the chimeric protein SBR-GLU significantly enhanced mucosal immune responses to SBR and GLU and systemic immune responses to SBR . The ability of SBR-GLU to induce responses effective in protection against colonization of S . mutans suggests its potential as a vaccine antigen for dental caries.

Infect Immun, 2002 Dec, 70(12), 6646 - 51
EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis; Collin M et al.; The human pathogen Streptococcus pyogenes primarily infects the upper respiratory tract and skin, but occasionally it disseminates and causes severe invasive disease with high mortality . This study revealed that the activity of extracellular EndoS, which hydrolyzes the functionally important N-linked oligosaccharides on opsonizing immunoglobulin G (IgG), contributes to increased survival of S . pyogenes in human blood ex vivo . The inability to kill the bacteria is due to reduced binding of IgG to Fc receptors and impaired classical pathway-mediated activation of complement . In addition, the activity of extracellular SpeB, which cleaves IgG into Fc and Fab fragments, also increases bacterial survival . This suggests that S . pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system.

Infect Immun, 2002 Dec, 70(12), 6534 - 40
Construction of a novel transposon mutagenesis system useful in the isolation of Streptococcus parasanguis mutants defective in Fap1 glycosylation; Chen Q et al.; Streptococcus parasanguis, a primary colonizer of the tooth surface, has long, peritrichous fimbriae . A fimbria-associated protein, Fap1, is identified as an adhesin of S . parasanguis FW213 . The mature Fap1 protein is glycosylated, and the glycosylation is required for fimbria biogenesis and bacterial adhesion . Little is known about the mechanism of Fap1 glycosylation due to the lack of identifiable mutants . A novel transposon mutagenesis system was established and used to generate a mutant library . Screening of the library with a monoclonal antibody specific for a glycan epitope of Fap1 yielded six mutants with decreased expression levels of surface-associated glycosylated Fap1 protein . Southern blot analyses revealed that three of the mutants had the transposon inserted in the fap1 locus, whereas the other three mutants had insertions in other genes . Among the latter three mutants, two expressed Fap1 polypeptides on which no glycosylation was detected by glycan-specific antibodies; the other mutant expressed a partially glycosylated Fap1 polypeptide . These data suggest that three mutants were isolated with defects in genes implicated in Fap1 glycosylation.

Am J Manag Care, 2002 Nov, 8(11), 988 - 94
Antibiotic resistance: the Iowa experience; Bell N; BACKGROUND: In the past 10 years, the number of strains of Streptococcus pneumoniae and other common respiratory pathogens that are resistant to penicillin has increased . OBJECTIVE: The Iowa Department of Public Health convened a multidisciplinary task force in January 1998 to develop strategies to combat antibiotic resistance in the state because they were alarmed by these reports . METHODS: Within 18 months, the task force implemented statewide surveillance of resistant organisms and posted information about the surveillance on the Internet, distributed a public health guide on judicious antibiotic use and infection control measures to 7500 healthcare providers, and held a press conference to inform the public about antibiotic resistance . The task force collaborated with several major insurers in the state to profile the top prescribers of antibiotic agents in their plan . RESULTS AND CONCLUSIONS: The profiling and educational interventions led to a substantial decrease in both overall antibiotic prescribing and drug costs . Other states may want to undertake similar programs to help protect their citizens from infections caused by resistant pathogens.

New Microbiol, 2002 Oct, 25(4), 495 - 7
Effect of date extract on growth and hemolytic activity of Streptococcus pyogenes; Hammad M et al.; The effect of date extract on growth and hemolytic activity of S . pyogenes was examined . It was found that 5% DE caused 78 % growth inhibition . However, 20% DE inhibited the growth by 86% . 5% DE inhibited hemolysin and streptolysin O activities by 43% and 24% respectively,while 20% caused 95 and 91 %inhibition.

Antimicrob Agents Chemother, 2002 Dec, 46(12), 3987 - 90
Erythromycin-resistant pharyngeal isolates of Streptococcus pyogenes recovered in Italy; Dicuonzo G et al.; Three classes of macrolide resistance phenotypes and three different erythromycin resistance determinants were found among 127 erythromycin-resistant group A streptococcal (GAS) isolates recovered from 355 (35.8%) pediatric pharyngitis patients in Rome, Italy . According to emm and sof sequence typing results, erythromycin-resistant isolates comprised 11 different clonal types . Remarkably, 126 of the 127 macrolide-resistant isolates were serum opacity factor (sof) gene positive . These data suggest a strong association between macrolide resistance and the presence of sof among GAS isolates recovered from Italian pediatric pharyngitis patients.

Antimicrob Agents Chemother, 2002 Dec, 46(12), 3756 - 64
Genes involved in bacitracin resistance in Streptococcus mutans; Tsuda H et al.; Streptococcus mutans is resistant to bacitracin, which is a peptide antibiotic produced by certain species of BACILLUS: The purpose of this study was to clarify the bacitracin resistance mechanism of S . mutans . We cloned and sequenced two S . mutans loci that are involved in bacitracin resistance . The rgp locus, which is located downstream from rmlD, contains six rgp genes (rgpA to rgpF) that are involved in rhamnose-glucose polysaccharide (RGP) synthesis in S . mutans . The inactivation of RGP synthesis in S . mutans resulted in an approximately fivefold-higher sensitivity to bacitracin relative to that observed for the wild-type strain Xc . The second bacitracin resistance locus comprised four mbr genes (mbrA, mbrB, mbrC, and mbrD) and was located immediately downstream from gtfC, which encodes the water-insoluble glucan-synthesizing enzyme . Although the bacitracin sensitivities of mutants that had defects in flanking genes were similar to that of the parental strain Xc, mutants that were defective in mbrA, mbrB, mbrC, or mbrD were about 100 to 120 times more sensitive to bacitracin than strain Xc . In addition, a mutant that was defective in all of the mbrABCD genes and rgpA was more sensitive to bacitracin than either the RGP or Mbr mutants . We conclude that RGP synthesis is related to bacitracin resistance in S . mutans and that the mbr genes modulate resistance to bacitracin via an unknown mechanism that is independent of RGP synthesis.

Antimicrob Agents Chemother, 2002 Dec, 46(12), 3750 - 5
A novel efflux system in inducibly erythromycin-resistant strains of Streptococcus pyogenes; Giovanetti E et al.; Streptococcus pyogenes strains inducibly resistant (iMLS phenotype) to macrolide, lincosamide, and streptogramin B (MLS) antibiotics can be subdivided into three phenotypes: iMLS-A, iMLS-B, and iMLS-C . This study focused on inducibly erythromycin-resistant S . pyogenes strains of the iMLS-B and iMLS-C types, which are very similar and virtually indistinguishable in a number of phenotypic and genotypic features but differ clearly in their degree of resistance to MLS antibiotics (high in the iMLS-B type and low in the iMLS-C type) . As expected, the iMLS-B and iMLS-C test strains had the erm(A) methylase gene; the iMLS-A and the constitutively resistant (cMLS) isolates had the erm(B) methylase gene; and a control M isolate had the mef(A) efflux gene . mre(A) and msr(A), i.e., other macrolide efflux genes described in gram-positive cocci, were not detected in any test strain . With a radiolabeled erythromycin method for determination of the intracellular accumulation of the drug in the absence or presence of an efflux pump inhibitor, active efflux of erythromycin was observed in the iMLS-B isolates as well as in the M isolate, whereas no efflux was demonstrated in the iMLS-C isolates . By the triple-disk (erythromycin plus clindamycin and josamycin) test, performed both in normal test medium and in the same medium supplemented with the efflux pump inhibitor, under the latter conditions iMLS-B and iMLS-C strains were no longer distinguishable, all exhibiting an iMLS-C phenotype . In conjugation experiments with an iMLS-B isolate as the donor and a Rif(r) Fus(r) derivative of an iMLS-C isolate as the recipient, transconjugants which shared the iMLS-B type of the donor under all respects, including the presence of an efflux pump, were obtained . These results indicate the existence of a novel, transferable efflux system, not associated with mef(A) or with other known macrolide efflux genes, that is peculiar to iMLS-B strains . Whereas the low-level resistance of iMLS-C strains to MLS antibiotics is apparently due to erm(A)-encoded methylase activity, the high-level resistance of iMLS-B strains appears to depend on the same methylase activity plus the new efflux system.

J Med Microbiol, 2002 Oct, 51(10), 837 - 43
Purification of native alpha-enolase from Streptococcus pneumoniae that binds plasminogen and is immunogenic; Whiting GC et al.; Many pathogenic bacteria express plasminogen receptors on their surface, which may play a role in the dissemination of organisms by binding plasminogen that, when converted to plasmin, can digest extracellular matrix proteins . A 45-kDa protein was purified from Streptococcus pneumoniae and confirmed as an alpha-enolase by its ability to catalyse the dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate and by N-terminal sequencing . The activity of alpha-enolase was found in the cytoplasm and in whole cells . Activity was also demonstrated in cell wall fractions, which confirmed that alpha-enolase is a cytoplasmic antigen also expressed on the surface of S . pneumoniae . The plasminogen-binding activity of alpha-enolase was examined by Western blot, which showed that purified alpha-enolase was able to bind human plasminogen . Immunoblots of the purified 45-kDa alpha-enolase with 22 sera from patients with pneumococcal disease showed binding in 15 cases, indicating that pneumococcal enolase is immunogenic.

Carbohydr Res, 2002 Nov 19, 337(21-23), 2353 - 8
Confirmation of the D configuration of the 2-substituted arabinitol 1-phosphate residue in the capsular polysaccharide from Streptococcus pneumoniae Type 17F; Jones C et al.; The absolute configuration of the 2-substituted arabinitol 1-phosphate residue present in the repeating unit of the capsular polysaccharide (CPS) from Streptococcus pneumoniae Type 17F is confirmed as D, based on a comparison of proton and carbon chemical shifts in a synthetic oligosaccharide and in an oligosaccharide derived from the CPS by degradation .

Carbohydr Res, 2002 Nov 19, 337(21-23), 2023 - 36
Synthesis and conformational analysis of a pentasaccharide corresponding to the cell-wall polysaccharide of the Group A Streptococcus; Hoog C et al.; The synthesis and conformational analysis of a pentasaccharide corresponding to a fragment of the cell-wall polysaccharide (CWPS) of the bacteria Streptococcus Group A are described . The polysaccharide consists of alternating alpha-(1 --> 2)- and alpha-(1 --> 3)-linked L-rhamnopyranose (Rhap) residues with branching 2-acetamido-2-deoxy-D-glucopyranose (GlcpNAc) residues linked beta-(1 --> 3) to alternate rhamnose rings . The pentasaccharide is of interest as a possible terminal unit on the CWPS, for use in a vaccine . The syntheses employed a trichloroacetimidate glycosyl donor . Molecular dynamics (MD) calculations of the pentasaccharide with the force fields CVFF and PARM22, both in gas phase and with explicit water present, gave different predictions for the flexibility and preferred conformational space . Metropolis Monte Carlo (MMC) calculations with the HSEA force field were also performed . Experimental data were obtained from 1D transient NOE measurements . Complete build-up curves were compared to those obtained by full relaxation matrix calculations in order to derive a model of the conformation . Overall, the best fit between experimental and calculated data was obtained with MMC simulations using the HSEA force field . Molecular dynamics and MMC simulations of a tetrasaccharide corresponding to the Group A-variant polysaccharide, which differs in structure from Group A in lacking the GlcpNAc residues, were also performed for purposes of comparison .

Curr Microbiol, 2003 Jan, 46(1), 18 - 23
Factors affecting the antibacterial activity of the ruminal bacterium, Streptococcus bovis HC5; Mantovani HC et al.; Streptococcus bovis HC5 inhibits a variety of S . bovis strains and other Gram-positive bacteria, but factors affecting this activity had not been defined . Batch culture studies indicated that S . bovis HC5 did not inhibit S . bovis JB1 (a non-bacteriocin-producing strain) until glucose was depleted and cells were entering stationary phase, but slow-dilution-rate, continuous cultures (0.2 h(-1)) had as much antibacterial activity as stationary-phase batch cultures . Because the activity of continuous cultures (0.2-1.2 h(-1)) was inversely related to the glucose consumption rate, it appeared that the antibacterial activity was being catabolite repressed by glucose . When the pH of continuous cultures (0.2 h(-1)) was decreased from 6.7 to 5.4, antibacterial activity doubled, but this activity declined at pH values less than 5.0 . Continuous cultures (0.2 h(-1)) that had only ammonia as a nitrogen source had antibacterial activity, and large amounts of Trypticase (10 mg ml(-1)) caused only a 2.0-fold decline in the amount of HC5 cell-associated protein that was needed to prevent S . bovis JB1 growth . Because S . bovis HC5 was able to produce antibacterial activity over a wide range of culture conditions, there is an increased likelihood that this activity could have commercial application.

Birth, 2002 Dec, 29(4), 285 - 90
Barriers to implementing the group B streptococcal prevention guidelines; Cardenas V et al.; BACKGROUND: Group B streptococcal disease is the leading cause of neonatal sepsis in the United States . We assessed predictors of compliance with the consensus guidelines for perinatal group B streptococcus disease prevention at two Group Health Cooperative hospitals . METHODS: A descriptive and cohort analysis was conducted of failure to comply with the screening-based approach to group B streptococcus prevention among singleton birth pregnancies in two Group Health Cooperative hospitals, September 1, 1996 to December 31, 1997 . We studied determinants of failure to screen pregnant women for group B streptococcus at 35 to 37 weeks' gestation and failure to deliver intrapartum antibiotic prophylaxis to Group B streptococcus-positive women . RESULTS: Nearly 28 percent of 1969 women delivering at two Group Health Cooperative hospitals were not screened appropriately for group B streptococcus . Women who were not screened properly were more likely to be in their teens . A short length of hospital stay before delivery was the strongest predictor of the lack of administration of intrapartum antibiotic prophylaxis to infected multiparas at delivery . Group B streptococcus-positive women without pregnancy complications were less likely to receive intrapartum antibiotic prophylaxis than infected women with complications . CONCLUSIONS: The findings of this study suggest that to improve group B streptococcus disease prevention, screening efforts should focus on teenage women, and intrapartum antibiotic prophylaxis delivery efforts should be aimed at low-risk women with precipitous labor.

Arthritis Rheum, 2002 Nov, 46(11), 3015 - 25
Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis; Massa M et al.; OBJECTIVE: To identify self T cell epitopes associated with proinflammatory immune responses and clinically active juvenile dermatomyositis (juvenile DM) . The target of our search for relevant epitopes was represented by amino acid sequences shared between human skeletal myosin and Streptococcus pyogenes M5 protein . The long-term objective of the project is to identify suitable targets for immunotherapy of the disease . METHODS: We used computerized algorithms to identify putative agretopes on both the human myosin and Streptococcus M5 proteins . Direct binding assays for homolog peptides were used to confirm such predictions . Antigenicity and functional cross-reactivity were evaluated by cytotoxicity assays and by measurement of cytokine levels . Specific T cells were isolated by T cell capture, and T cell receptor (TCR) V(beta) gene usage was identified by reverse transcriptase-polymerase chain reaction . RESULTS: We identified peptides that are targets of disease-specific cytotoxic T cell responses . T cell reactivity against the self peptides correlates with clinical signs of early, active myositis . Such reactivity is accompanied by production of proinflammatory cytokines, which may contribute to the damage . T cell cross-recognition of bacterial and human homologs was shown functionally as well as by sorting peptide-specific T cells and identifying oligoclonal and largely overlapping TCR V(beta) gene usage . CONCLUSION: These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.

Microbiology, 2002 Nov, 148(Pt 11), 3347 - 52
Bovicin HC5, a bacteriocin from Streptococcus bovis HC5; Mantovani HC et al.; Previous work indicated that Streptococcus bovis HC5 had significant antibacterial activity, and even nisin-resistant S . bovis JB1 cells could be strongly inhibited . S . bovis HC5 inhibited a variety of Gram-positive bacteria and the spectrum of activity was similar to monensin, a commonly used feed additive . The crude extracts (ammonium sulfate precipitation) were inactivated by Pronase E and trypsin, but the activity was resistant to heat, proteinase K and alpha-chymotrypsin . Most of the antibacterial activity was cell associated, but it could be liberated by acidic NaCl (100 mM, pH 2.0) without significant cell lysis . When glycolysing S . bovis JB1 cells were treated with either crude or acidic NaCl extracts, intracellular potassium declined and this result indicated the antibacterial activity was mediated by a pore-forming peptide . The peptide could be purified by HPLC and matrix-assisted laser desorption ionization time-of-flight analysis indicated that it had a molecular mass of approximately 2440 Da . The terminal amino acid sequence was VGXRYASXPGXSWKYVXF . The unnamed amino acid residues (designated by X) had approximately the same position as dehydroalanines found in some lantibiotics, but samples that were reduced and alkylated prior to Edman degradation did not have cysteine residues . The only other bacteriocin that had significant similarity was the lantibiotic precursor of Streptococcus pyogenes SF370, but the identity was only 55% . Based on these results, the bacteriocin of S . bovis HC5 appears to be novel and the authors now designate it as bovicin HC5.

Avian Pathol, 2002 Oct, 31(5), 421 - 3
Failure of a low virulence Streptococcus gallolyticus serotype 1 strain to immunize pigeons against streptococcosis; Kimpe A et al.; Ten pigeons were inoculated intravenously with the low virulence Streptococcus gallolyticus strain PDH 827, which belongs to serotype 1, supernatant phenotype A(-)T2 . The birds did not develop clinical disease but shed S . gallolyticus in their faeces, and antibodies against the bacterium were detected in post-inoculation plasma samples of all birds . Seven weeks later, these pigeons, as well as 14 control pigeons, were challenged intravenously with the highly virulent S . gallolyticus strain STR 357, which also belongs to serotype 1 but to the supernatant phenotype A(+)T1 . Post-inoculation morbidity in the immunized group amounted to 90%, demonstrating that no protective immunity had been built up after the first infection . These findings indicate that serotype-specific antigens are not, or at least not solely, involved in induction of protection against S . gallolyticus septicaemia in pigeons.

Clin Microbiol Infect, 2002, 8 Suppl 2, 1 - 11
Outcomes in lower respiratory tract infections and the impact of antimicrobial drug resistance; Metlay JP et al.; Numerous published studies have documented the rapid rise in antimicrobial drug resistance among common respiratory pathogens, particularly Streptococcus pneumoniae . Yet, surprisingly few studies have evaluated the impact of these in vitro findings on clinical outcomes . Outcomes research is the measurement of the impact of illness and the effect of treatment on clinically relevant end-points . Studies of patients with community-acquired pneumonia have established certain expected rates of outcomes, including mortality, clinical complications, and time to resolution of symptoms . Recent studies have identified specific processes of care and treatment choices that have an impact upon these outcomes . However, there are no well-controlled studies that provide definitive estimates of the magnitude of the impact of antimicrobial therapy on these outcomes for patients with community-acquired pneumonia or other respiratory tract infections, such as acute exacerbations of chronic bronchitis . Most studies of the impact of drug resistance on outcomes for patients with respiratory tract infections have focused on the impact of beta-lactam drug resistance on outcomes for patients with community-acquired pneumococcal pneumonia . In general, these studies have demonstrated that outcomes are not affected by current levels of drug resistance, but most studies are hampered by small sample size, inability to control adequately for severity of illness and concordance of therapy, and inclusion of few subjects with high-level drug resistance . Additional studies are urgently needed to assess better whether the current empiric treatment guidelines are adequate or will need to be adjusted as patterns of resistance continue to evolve.

Cell Microbiol, 2002 Nov, 4(11), 751 - 8
The alpha C protein mediates internalization of group B Streptococcus within human cervical epithelial cells; Bolduc GR et al.; Group B Streptococcus (GBS) is the leading cause of bacterial chorioamnionitis and neonatal pneumonia, sepsis, and meningitis . Deletion of the alpha C protein gene (bca) attenuates the virulence of GBS in an animal model; significant survival differences in the first 24 h of infection suggest a pathogenic role for the alpha C protein early in the infection process . We examined the role of alpha C protein in the association between GBS and mucosal surfaces using a human cervical epithelial cell line, ME180 . Fluorescent and confocal microscopy and flow cytometry demonstrated that 9-repeat alpha C protein binds to the surface of ME180 cells . Isolated N-terminal region of this protein also binds to these cells and competitively inhibits binding of the full protein . Wild-type GBS strain A909 and the bca-null isogenic mutant JL2053 bound similarly to the surface of ME180 cells . However, A909 entered these cells threefold more . Internalization of A909 was inhibited with 2- and 9-repeat alpha C and with N-terminal region alone but not by repeat region-specific peptide . Translocation across polarized ME180 membranes was fivefold greater for A909 than for JL2053 . These findings suggest a role for the alpha C protein in interaction with epithelial surfaces and initiation of infection.

Environ Health Perspect, 2002 Oct, 110 Suppl 5, 871 - 5
A role for associated transition metals in the immunotoxicity of inhaled ambient particulate matter; Zelikoff JT et al.; Epidemiologic studies demonstrate that infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals following exposure to ambient particulate matter (PM) . This laboratory has previously demonstrated that a single inhalation exposure of Streptococcus pneumoniae-infected rats to concentrated ambient PM(2.5) (particulate matter with aerodynamic diameter < or =2.5 microm) from New York City (NYC) air exacerbates the infection process and alters pulmonary and systemic immunity . Although these results provide some basis for explaining the epidemiologic findings, the identity of specific PM constituents that might have been responsible for the worsening pneumonia in exposed hosts remains unclear . Thus, studies were performed to correlate the physicochemical attributes of ambient PM(2.5) with its in vivo immunotoxicity to identify and characterize the role of constitutive transition metals in exacerbating an ongoing streptococcal infection . Uninfected or previously infected rats were exposed in the laboratory to soluble divalent Fe, Mn, or Ni chloride salts . After exposure, uninfected rats were sacrificed and their lungs were lavaged . Lungs from infected hosts were used to evaluate changes in bacterial clearance and effects of exposure on the extent/severity of infection . Results demonstrated that inhalation of Fe altered innate and adaptive immunity in uninfected hosts, and both Fe and Ni reduced pulmonary bacterial clearance in previously infected rats . The effects on clearance produced in infected Fe-exposed rats were similar to those seen in infected rats exposed to ambient NYC PM . Taken together, these studies demonstrate that inhaled ambient PM can worsen the outcome of an ongoing pulmonary infection and that associated Fe may play some role in the immunotoxicity.

South Med J, 2002 Oct, 95(10), 1204 - 6
Listeria monocytogenes-induced monomicrobial non-neutrocytic bacterascites; Jammula P et al.; Spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis of the liver . The organisms most commonly involved in this infection are gram-negative bacteria like Escherichia coli and Klebsiella pneumoniae, and gram-positive bacteria like Streptococcus pneumoniae and Staphylococcus aureus . Listeria monocytogenes is an uncommon gram-positive bacillus implicated in infections in neonates, pregnant females, the elderly, and immunocompromised patients . Listeria monocytogene-induced SBP is rare, with less than 40 cases reported in the medical literature . Monobacterial non-neutrocytic bacterascites (MNB) is a variant of SBP, where the ascitic fluid culture is positive but the ascitic neutrophil count is less than 250/mm3 . Forty percent of these patients will subsequently have SBP . Only 2 cases of MNB from L monocytogenes have previously been reported . We report a case of MNB in a patient with cirrhosis whose ascitic neutrophil count was 164/mm', but Gram stain and microbiologic culture showed the growth of L monocytogenes.

J Infect Dis, 2002 Dec 1, 186 Suppl 2, S220 - 4
Strategy of Escherichia coli for crossing the blood-brain barrier; Kim KS; A major contributing factor to high mortality and morbidity associated with bacterial meningitis is the incomplete understanding of the pathogenesis of this disease: It is unclear how circulating bacteria cross the blood-brain barrier (BBB) . Recent studies with Escherichia coli K1 show that successful traversal of the BBB requires a high degree of bacteremia, invasion of brain microvascular endothelial cells (BMEC), host cell actin cytoskeleton rearrangements and related signaling pathways, and traversal of the BBB as live bacteria . Several microbial determinants such as the K1 capsule, OmpA, Ibe proteins, AslA, TraJ, and CNF1 contribute to BMEC invasion . Of interest, E . coli K1 trafficking mechanisms differ from those of other meningitis-causing bacteria such as Listeria monocytogenes and group B streptococcus . Complete understanding of bacteria-BMEC interactions contributing to translocation of the BBB should assist in developing novel strategies to prevent bacterial meningitis.

J Biol Chem, 2003 Feb 14, 278(7), 4510 - 5 Epub 2002 Nov 06.
The kinetic mechanism of phosphomevalonate kinase; Pilloff D et al.; Phosphomevalonate kinase catalyzes an essential step in the so-called mevalonate pathway, which appears to be the sole pathway for the biosynthesis of sterols and other isoprenoids in mammals and archea . Despite the well documented importance of this pathway in the cause and prevention of human disease and that it is the biosynthetic root of an enormous diverse class of metabolites, the mechanism of phosphomevalonate kinase from any organism is not yet well characterized . The first structure of a phosphomevalonate kinase from Streptococcus pneumoniae was solved recently . The enzyme exhibits an atypical P-loop that is a conserved defining feature of the GHMP kinase superfamily . In this study, the kinetic mechanism of the S . pneumoniae enzyme is characterized in the forward and reverse directions using a combination of classical initial-rate methods including alternate substrate inhibition using ADPbetaS . The inhibition patterns strongly support that in either direction the substrates bind randomly to the enzyme prior to chemistry, a random sequential bi-bi mechanism . The kinetic constants are as follows: k(cat(forward)) = 3.4 s(-1), K(i(ATP)) = 137 microm, K(m(ATP)) = 74 microm, K(i(pmev)) = 7.7 microm, K(m(pmev)) = 4.2 microm; k(cat(reverse)) = 3.9 s(-1), K(i(ADP)) = 410 microm, K(m(ADP)) = 350 microm, K(i(ppmev)) = 14 microm, K(m(ppmev)) = 12 microm, where pmev and ppmev represent phosphomevalonate and diphosphomevalonate, respectively.

Carbohydr Res, 2002 Oct 11, 337(19), 1715 - 22
Synthesis of oligosaccharides corresponding to Streptococcus pneumoniae type 9 capsular polysaccharide structures; Alpe M et al.; Two trisaccharides, alpha-D-Galp-(1-->3)-beta-D-ManpNAc-(1-->4)-beta-D-Glcp and alpha-D-Glcp-(1-->3)-beta-D-ManpNAc-(1-->4)-beta-D-Glcp, corresponding to structures from Streptococcus pneumoniae capsular polysaccharides type 9A, L, V and type 9N, respectively, have been synthesised as 2-aminoethyl glycosides and as protected TMSE glycosides . Ethyl thioglycosides were used as glycosyl donors and NIS/TfOH (in CH(2)Cl(2) for beta-linkages) and DMTST (in Et(2)O for alpha-linkages) as promoters in the glycosylations . The beta-ManNAc motif was introduced at the disaccharide level by azide displacement of a 2-O-triflate with beta-D-gluco configuration . The protecting group patterns allow continued syntheses of larger structures.

Obstet Gynecol, 2002 Nov, 100(5 Pt 2), 1126 - 9
Streptococcus bovis bacteremia and fetal death; White BA et al.; BACKGROUND: Preterm premature rupture of membranes leading to intraamniotic infection and fetal death may be due to unusual bacterial species . CASE: A young multipara presented at 24 weeks and 6 days' gestation with rupture of membranes of 2 days' duration . She was febrile and hypotensive . No fetal heart activity was noted . Antibiotics, fluid resuscitation, and oxytocin were begun with delivery of a 798-g stillborn fetus . Maternal and fetal cultures demonstrated Streptococcus bovis as the infectious agent . CONCLUSION: Unusual bacteria such as S bovis are sometimes responsible for severe maternal and fetal infections . Aggressive fluid resuscitation, uterine evacuation, and triple antibiotic therapy until culture results are available are indicated.

FEMS Microbiol Lett, 2002 Oct 29, 216(1), 23 - 32
Topological characterization of the essential Escherichia coli cell division protein FtsW; Lara B et al.; The membrane topology of Escherichia coli FtsW, a 46-kDa essential protein, was analyzed using a set of 28 ftsW-alkaline phosphatase (ftsW-phoA) and nine ftsW-beta-lactamase (ftsW-bla) gene fusions obtained by in vivo and in vitro methods . The alkaline phosphatase activities or resistance pattern of cells expressing the FtsW-PhoA or FtsW-Bla fusions confirmed only eight out of 10 transmembrane segments predicted by computational methods . After comparison with the recent topology of Streptococcus pneumoniae FtsW, we could identify all the fusions in absolute agreement with the predicted model: N-terminal and C-terminal ends in the cytoplasm, 10 transmembrane segments and one large loop of 67 amino acids (E240-E306) located in the periplasm.

Australas J Dermatol, 2002 Nov, 43(4), 274 - 7
Factors supporting sustainability of a community-based scabies control program; Wong LC et al.; Scabies remains a major problem in Aboriginal communities within the Northern Territory of Australia . Secondary skin infection with Group A streptococcus (GAS) is very common and post-streptococcal disease rates remain high . Treating families in isolation will have only limited success, as reinfection frequently occurs as a result of the high levels of movement between households and communities . We describe the results of a successful community intervention to reduce scabies and GAS skin infection in one of the largest Aboriginal communities in the Northern Territory, 15 months post-intervention, and we discuss factors that have led to the success and sustainability of the program.

Folia Microbiol (Praha), 2002, 47(4), 391 - 400
Isolation and partial characterization of an antibacterial substance produced by Enterococcus faecium; Pantev A et al.; A strain of Enterococcus faecium isolated from Bulgarian yellow cheese "kashkaval" produced a bacteriocin-like substance named enterococcin A 2000 . The antibacterial substance had a low molar mass (< 2 kDa), was relatively stable toward heat but was sensitive to selected proteolytic enzymes . It was active against Gram-positive bacteria including enterococci, such as Listeria, Bacillus and Streptococcus, and also against Gram-negative E . coli . Production of enterococcin A 2000 has a maximum near the end of the exponential phase of producer growth . The peptide was purified by ammonium sulfate precipitation, butanol extraction, followed by cation-exchange chromatography and reversed-phase chromatography . A partial sequence of purified enterococcin A 2000 indicated that this substance does not belong to the class IIa of bacteriocins presenting the consensus anti-Listeria motif YGNGV.

Pediatr Int, 2002 Dec, 44(6), 647 - 51
Investigation of risk factors for tonsillopharyngitis with macrolide resistant Streptococcus pyogenes in Turkish children; Ciftci E et al.; Background: Streptococcus pyogenes is the most important causative agent of tonsillopharyngitis . Although penicillin is the drug of choice in streptococcal tonsillopharyngitis, macrolides are recommended drugs in patients who have an allergy to penicillin . However, resistance to macrolides is an important problem in some regions of the world . Risk factors for resistance development have not been investigated sufficiently . Objectives: To investigate the risk factors for the development of tonsillopharyngitis with macrolide resistant S . pyogenes . Methods: Three hundred and forty-five children with tonsillopharyngitis caused by S . pyogenes were investigated for various risk factors . Streptococcus pyogenes isolated from children's throat culture were examined for erythromycin, clarithromycin and azithromycin susceptibility . Results: Two hundred and sixty-three children were found eligible for the analysis of risk factors . Resistances to erythromycin, clarithromycin and azithromycin were detected as 3.8, 4.2 and 4.2%, respectively . Macrolide use of the family members in the last 3 months (odds ratio = 7.04, P = 0.005) has been determined to be a risk factor for the development of tonsillopharyngitis with macrolide resistant S . pyogenes . Conclusion: Restriction of macrolide antibiotic use appears to be the most important measure to prevent the development of tonsillopharyngitis with resistant S . pyogenes.

Trends Microbiol, 2002 Nov, 10(11), 515 - 21
The fundamental contribution of phages to GAS evolution, genome diversification and strain emergence; Banks DJ et al.; The human bacterial pathogen group A Streptococcus (GAS) causes many different diseases including pharyngitis, tonsillitis, impetigo, scarlet fever, streptococcal toxic shock syndrome, necrotizing fasciitis and myositis, and the post-infection sequelae glomerulonephritis and rheumatic fever . The frequency and severity of GAS infections increased in the 1980s and 1990s, but the cause of this increase is unknown . Recently, genome sequencing of serotype M1, M3 and M18 strains revealed many new proven or putative virulence factors that are encoded by phages or phage-like elements . Importantly, these genetic elements account for an unexpectedly large proportion of the difference in gene content between the three strains . These new genome-sequencing studies have provided evidence that temporally and geographically distinct epidemics, and the complex array of GAS clinical presentations, might be related in part to the acquisition or evolution of phage-encoded virulence factors . We anticipate that new phage-encoded virulence factors will be identified by sequencing the genomes of additional GAS strains, including organisms non-randomly associated with particular clinical syndromes.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 May, 37(3), 222 - 4
The relativity between Streptococcus sanguis group and coronary heart disease; Deng S et al.; OBJECTIVE: To study the relativity between Streptococcus sanguis group (SSG) and coronary heart disease (CHD) . METHODS: 41 individuals were diagnosed with CHD and 18 normals served as controls . All of them had undergone coronary angiography . Their social class (including education and wages), smoking, drinking, blood lipids and oral health were also recorded . SSG in saliva and subgingival plaque were cultivated in NAYS-B agar plates and counted . SSG were identified into species with routine biochemical reaction and AP-PCR . RESULTS: In the multiple step regression analysis, the amount of SSG in saliva and subgingival plaque were positively associated with severe coronary atheromatosis after adjusting the classical risk factors of CHD . The average amount of SSG in saliva was (435 +/- 422) x 10(8) CFU/L in CHD group and (358 +/- 540) x 10(8) CFU/L in control group, F = 2.72, P = 0.08; the average amount of SSG in incisor was (331 +/- 484) x 10(7) CFU/L in CHD group and (98 +/- 164) x 10(7) CFU/L in control group, F = 5.54, P = 0.02; the average amount of SSG in molar was (352 +/- 381) x 10(7) CFU/L in CHD group and (185 +/- 232) x 10(7) CFU/L in control group, F = 2.86, P = 0.10 . S . sanguis and S . gordonii were more in CHD group than in control group (P < 0.05), whereas S . mitis and S . oralis were the same in two groups (P > 0.05) . CONCLUSION: The increase of SSG in oral floras may play an important role in the occurrence of CHD.

Can J Vet Res, 2002 Oct, 66(4), 240 - 8
Genetic diversity of Streptococcus suis serotypes 2 and 1/2 isolates recovered from carrier pigs in closed herds; Martinez G et al.; The aim of this study was to compare, by randomly amplified polymorphic DNA (RAPD), the diversity of Streptococcus suis serotypes 1/2 and 2 isolates recovered at slaughter houses from the tonsils of clinically healthy pigs . The pigs belonged to herds with or without clinical signs of S . suis disease . Overall, a low diversity was observed among isolates of serotype 1/2 . A representative isolate recovered from a diseased animal presented a relatively high similarity (85%), with most isolates recovered from carrier pigs, from herds either with or without clinical signs of S . suis disease . For serotype 2 isolates, a relatively high degree of heterogeneity was observed in the whole population . Two subpopulations were observed for serotype 2 isolates, which arose from herds with clinical signs . Interestingly, the representative isolate coming from the diseased pig was included in a small closed cluster, with 2 isolates recovered from carrier pigs belonging to the same herd . On the other hand, most of the S . suis serotype 2 isolates originating from herds with no history of S . suis disease, were closely related (90% similarity) . Furthermore, they presented different RAPD patterns from those originating from animals from the herd presenting S . suis clinical signs due to this serotype . Results suggest that, in the herds studied, clinical manifestations due to serotype 2 are probably related to the virulence of a specific isolate . Conversely, for the herd affected with serotype 1/2, clinical manifestations of the disease were more likely to be the result of inherent herd factors than the virulence of the specific isolate.

Int Dent J, 2002 Oct, 52(5), 325 - 9
Clinical and microbiological effects of local chlorhexidine applications; Frentzen M et al.; AIM: To study the effects of an application of chlorhexidine varnish (40%) on dental plaque . DESIGN: Randomised controlled clinical trial . SUBJECTS: 40 patients (50% females), aged 25-34 years after undergoing any necessary restorative treatment . Exactly one half of these individuals practiced good oral hygiene, the efforts of the others were poor . METHOD: Test groups received a chlorhexidine varnish application, the control group received a placebo varnish . Initially and after 2 and 6 weeks, a modified Dentocult SM-test, bleeding on probing, and a plaque index (Quigley-Hein) were recorded . RESULTS: In contrast to the control group, improvements in plaque index and bleeding on probing scores were found in patients with poor oral hygiene . The results of the Dentocult SM-tests showed a considerable reduction of streptococcus colonisation . The test group with good oral hygiene showed only slight improvement of the examined indices after chlorhexidine application . The index parameters of all patients of the placebo groups remained unchanged over the examination time period . CONCLUSION: The application of a chlorhexidine varnish reduced the quantity of the Streptococcus mutans colonies significantly and improved clinical parameters in patients with elevated plaque accumulation.

J Chemother, 2002 Jul, 14 Suppl 3, 42 - 56
Clinical and public health implications of macrolide-resistant Streptococcus pneumoniae; Moellering RC Jr et al.; Macrolide resistance among Streptococcus pneumoniae is a growing global concern, although its specific impact on public health is not currently well defined . A Consensus Working Group was convened in March 2001 to address whether credible, scientific data substantiate macrolide resistance in S . pneumoniae as: (i) producing significant morbidity; (ii) creating attendant health and economic burdens; (iii) constituting a public health threat; and (iv) warranting intervention, including development of new antibiotics with efficacy against these strains . Despite the limitations of available clinical data, concern about the possibility of treatment failure with macrolides is being expressed in clinical practice and in formal treatment guidelines, threatening the important role of these agents in the treatment of respiratory tract infections . Further studies are required to monitor and control macrolide resistance and evaluate settings in which macrolide treatment failures are occurring, and new therapeutic interventions are needed.

J Chemother, 2002 Jul, 14 Suppl 3, 31 - 41
The rise of fluoroquinolone resistance: fact or fiction; Ferraro MJ; Fluoroquinolone antibiotics have been available since the 1980s when ciprofloxacin and norfloxacin were licensed . Structural revisions of the quinolone molecule have provided new compounds that were well suited to the treatment of upper and lower community-acquired respiratory tract infections, having good activity against Streptococcus pneumoniae . Nevertheless, it was only a matter of time before the pneumococcus developed effective resistance against these new agents . There are populations of fluoroquinolone-resistant S . pneumoniae and, more worryingly, many of these strains are also resistant to penicillin and to macrolides . Surveillance studies such as PROTEKT (Prospective, Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) can provide an early warning system and, with the provision of global surveillance on a local level, can assist in the selection of empirical antibiotic treatment . The new ketolide antibiotic, telithromycin, has excellent activity against the major community-acquired respiratory pathogens (including atypical/intracellular organisms), and has the advantage of retaining its activity against strains of S . pneumoniae that are resistant to penicillin, macrolides and fluoroquinolones.

J Chemother, 2002 Jul, 14 Suppl 3, 25 - 30
Prevalence and characterization of macrolide resistance in clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes from North America; Hoban DJ; Resistance to macrolides is not a new phenomenon but it deserves attention because of the widespread use of these agents and their inclusion in many clinical guidelines for respiratory tract infections . The most common mechanisms by which Streptococcus pneumoniae and Streptococcus pyogenes develop resistance to macrolides is by target site modification (erythromycin ribosome methylase, erm) and efflux of the drug out of the organisms (macrolide efflux, mef) . Target site modification may be of greater concern because it confers high-level resistance to all antimicrobials in the macrolide-lincosamide-streptograminB (MLSB) group . The genotype profiles of macrolide-resistant S . pneumoniae and S . pyogenes differ somewhat across regions in the US and between the US and Canada and other countries . There is some evidence for an association between macrolide resistance and treatment failure but this must be researched more fully . S . pneumoniae and S . pyogenes isolates resistant to macrolides are generally susceptible to ketolide antimicrobials because these agents bind more strongly to the relevant domain of the ribosomal subunit (withstanding erm resistance) and are less vulnerable to efflux compared to the macrolides.

Clin Diagn Lab Immunol, 2002 Nov, 9(6), 1328 - 31
Antimicrobial susceptibilities and serotype distribution of Streptococcus pneumoniae isolates from a Low socioeconomic area in Lima, Peru; Cullotta AR et al.; Streptococcus pneumoniae isolates were obtained from nasopharyngeal swabs taken from children living in a low socioeconomic area of Lima, Peru, to determine the rates of antimicrobial resistance and serotype distribution . A total of 146 nasopharyngeal isolates were collected from children from 3 to 38 months of age . Twenty-one clinical laboratory isolates from both sterile and nonsterile sites were obtained from a local hospital . Isolates with reduced susceptibilities to penicillin represented 15.1 and 42.9% of the nasopharyngeal and clinical isolates, respectively . For neither group of isolates did penicillin MICs exceed 1.5 micro g/ml, indicating only intermediate resistance . Thirty-two different serotypes were identified from the 146 nasopharyngeal isolates . The serotypes of the clinical isolates were represented among those 32 types . Isolates with reduced susceptibility to multiple antimicrobial agents were present in both settings . These findings indicate some of the highest rates of antimicrobial resistance in the region as well as a slightly different serotype distribution pattern from those of other South American countries . The 7-valent conjugate pneumococcal vaccines would only have a limited effect, providing coverage for about half of all isolates . Increasing rates of resistance in Peru necessitate an awareness of antimicrobial treatment practices and vaccination strategies.

J Biotechnol, 2003 Jan 9, 100(1), 33 - 41
Amplifying the cellular reduction potential of Streptococcus zooepidemicus; Chong BF et al.; The valuable pharmaceutical polymer, hyaluronic acid, is produced industrially using the gram-positive bacterium Streptococcus zooepidemicus . Synthesis of this polymer is a significant energetic burden upon the microorganism hence the native NADH oxidase gene was cloned and overexpressed to increase the energy yield of catabolism during aerobic cultivation on glucose . Elevated NADH oxidase levels led to a decline in lactic acid generation and prevented ethanol formation, leaving acetate as the main fermentation product . Biomass yield increased due to the energy gained from the formation of acetate . Evaluation of the acetate flux control coefficient over a range of NADH oxidase expression levels revealed that acetate production was sensitive to the NADH oxidase level . However, at high NADH oxidase levels, the acetate flux was mainly influenced by another factor . The concomitant excretion of pyruvate at high NADH oxidase levels suggested that the flux through the pyruvate dehydrogenase enzyme complex was limiting the conversion of pyruvate to acetate.

Anal Biochem, 2002 Oct 15, 309(2), 232 - 40
Development of a fluorescence resonance energy transfer assay for measuring the activity of Streptococcus pneumoniae DNA ligase, an enzyme essential for DNA replication, repair, and recombination; Chen XC et al.; DNA ligase is an enzyme essential for DNA replication, repair, and recombination in all organisms . Bacterial DNA ligases catalyze a NAD(+)-dependent DNA ligation reaction, i.e., the formation of a phosphodiester bond between adjacent 3'-OH and 5'-phosphate termini of dsDNA . Due to their essential nature, unique cofactor requirement, and widespread existence in nature, bacterial DNA ligases appear to be valuable targets for identifying novel antibacterial agents . To explore bacterial DNA ligases as antibacterial targets and further characterize them, we developed a simple, robust, homogeneous time-resolved fluorescence resonance energy transfer assay (TR-FRET) for measuring Streptococcus pneumoniae DNA ligase activity . This assay involves the use of one dsDNA molecule labeled with biotin and another dsDNA molecule labeled with Cy5, an acceptor fluorophore . During ligation reactions, the donor fluorophore europium (Eu(3+)) labeled with streptavidin was added to the assay mixtures, which bound to the biotin label on the ligated products . This in turn resulted in the FRET from Eu(3+) to Cy5 due to their close proximity . The formation of ligation products was measured by monitoring the emission at 665nm . This assay was validated by the experiments showing that the DNA ligase activity required NAD(+) and MgCl(2), and was inhibited by NMN and AMP, products of the ligase reaction . Using this assay, we determined the K(m) values of the enzyme for dsDNA substrates and NAD(+), and the IC(50) values of NMN and AMP, examined the effects of MgCl(2) and PEG(8000) on the enzyme activity, optimized the concentrations of Eu(3+) in the assay, and validated its utilities for high-throughput screening and biochemical characterizations of this class of enzymes.

Respir Med, 2002 Oct, 96(10), 805 - 11
Cephalosporin-resistant pneumococcal pneumonia: does it, affect outcome?
Ailani RK, Alimchandani A, Hidalgo J, Ailani R, Buckley J, DiGiovine B.
STUDY OBJECTIVES: Penicillin resistance has been reported in various studies to have no impact on the outcome of pneumococcal pneumonia . However, the importance of cephalosporin resistance has not been systematically studied . We conducted an analysis of patients with high-level cephalosporin-resistant Streptococcus pneumoniae pneumonia (H-CRSPP) . DESIGN: Retrospective matched, case-control study . SETTING: Two inner-city academic hospitals . PATIENTS: Twenty-six patients with H-CRSPP admitted to the hospital between 1995 and 1999 were identified . Each patient was matched with two controls with cephalosporin-sensitive but oxacillin-resistant pneumococcal pneumonia admitted during the same time period . Matching was done based on pneumonia severity of illness index (PSI) and for other factors . INTERVENTIONS: None . MEASUREMENTS AND RESULTS: We evaluated a number of outcomes including mortality length of stay in the hospital, and time to respond to treatment . Patients with H-CRSPP took longer to respond to treatment (6.5 +/- 0.9 days vs 4.1 +/- 0.7 days, P=0.05) and had a longer length of stay in hospital (15.4 +/- 2.2 days vs 92 +/- 1.6 days, P=0.02) . None of the other outcomes were different between the two groups . CONCLUSIONS: Overall, we have found that the presence of cephalosporin resistance does impact the course of pneumococcal pneumonia.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 Jul, 37(4), 281 - 3
Detection of cariogenic Streptococcus mutans by quantitative polymerase chain reaction; Wang J et al.; OBJECTIVE: To establish a kind of molecular biology clinical detective method to cariogenic S . mutans . METHODS: Using the coamplification of target and reference genes . One pair of specific primers were designed according to a portion of the dextranase (dexA) gene of S . mutans . The reference gene was plasmid pET23b DNA . The saliva samples of 196 children were quantitative detected . The PCR method was compared with the routine culture method . RESULTS: The rate of S . mutans counts >/= 10(8) CFU/L (colony-forming unit per millilitre) saliva by quantitative PCR was 91.3% . The results of coincidence rate between the new method and the routine way was 94.9% . CONCLUSIONS: The new quantitative detective method is fast and provides with high scoincidence rate and high specificity, so have extensive clinical practice foreground.

Zhonghua Kou Qiang Yi Xue Za Zhi, 2002 Jul, 37(4), 275 - 7
The effect of para-aminobenzoic acid on growth and metabolism of Porphyromonas gingivalis; Zhou X et al.; OBJECTIVE: To study the effect of para-aminobenzoic acid (PABA) on the growth and metabolism of Porphyromonas gingivalis (P.g) . METHODS: After adding different concentrations of PABA into the medium, anaerobic technique was applied to culture P.g . The products' A value and action of TLP was assayed, and P.g grew in the medium was observed by a scanning electron microscope . RESULTS: PABA promoted the growth of P.g and action of TLP, which would reach the highest level when PABA was 1 mg/L, and would decrease with the increasing of concentration of PABA . When the concentration arrived at 100 mg/L, PABA had no effect on them . In the mean time, PABA had effect on the form and adherence of P.g . When the concentration was 1 mg/L and 100 mg/L, this effect was strong, but as the concentration was 10 mg/L, the effect disappeared . CONCLUSIONS: PABA influences the growth and metabolism of P.g, which indicate that Streptococcus sanguis has regulative effect on the microecology of subgingival plaque.

J Paediatr Child Health, 2002 Dec, 38(6), 615 - 7
Low molecular weight heparin for neonatal thrombosis; Shama A et al.; The clinical course of a term neonate (birthweight 3.14 kg) who developed thrombosis of the left common and internal iliac veins on day 21 following recovery from Streptococcus mitis septicemia, with shock diagnosed on day 13, is reported . Subcutaneous low molecular weight heparin (LMWH) was commenced (1.5 mg/kg 12 hourly for 10 days) after 13 h of standard heparin infusion, due to difficulties in securing a peripheral venous access . The inflammation of the left leg was completely resolved by day 5 of LMWH therapy . Prothrombin time, activated prothrombin time and fibrinogen levels were within normal limits during LMWH therapy . Treatment-related side effects, such as thrombocytopenia and bleeding tendency were not noted . Doppler studies 6 weeks after discharge home on day 33 revealed complete resolution of the thrombus . Apart from septicaemia and shock, the presence of an indwelling central venous catheter and a history of untreated maternal diabetes were additional risk factors for thrombosis . Because it is as effective as standard heparin, LMWH may be a therapeutic option for thrombosis in high-risk neonates, particularly given its ease of administration by the subcutaneous route, predictable pharmacokinetics and reduced incidence of adverse effects such as bleeding complications.

Clin Infect Dis, 2002 Nov 15, 35(10), 1174 - 82 Epub 2002 Oct 21.
Antimicrobial use and serotype distribution of nasopharyngeal Streptococcus pneumoniae isolates recovered from Greek children younger than 2 years old; Syrogiannopoulos GA et al.; The serotype distribution of 781 nasopharyngeal pneumococcal isolates recovered from 2448 unselected children aged 2-23 months was studied . Only 3.9% of the children for whom cultures were performed attended day care centers . The proportions of pneumococcal isolates that belonged to serotypes related to the 7-, 9- and 11-valent conjugate pneumococcal vaccine were 65%, 66%, and 70%, respectively . The pneumococcal carriage rate among untreated children was 34%; the rates among children treated with antibiotics during the periods 1-30 or 31-60 days before the time of nasopharyngeal sampling were 25% and 36%, respectively . There was a significant positive association between antimicrobial use and carriage of antibiotic-resistant pneumococci, which belonged mainly to vaccine-related serotypes . The proportion of isolates that belonged to vaccine-related serotypes in untreated carriers was 72%; however, the proportions in carriers treated 1-30 days or 31-60 days before sampling were 66% and 56%, respectively . In the nasopharynx, antimicrobial use selects for antibiotic-resistant pneumococci, mainly of vaccine-related serotypes, whereas it may promote an increase in the frequency of colonization with nonvaccine serotypes.

J Clin Microbiol, 2002 Nov, 40(11), 4357 - 9
High rate of transmission of penicillin-resistant Streptococcus pneumoniae between parents and children; Hoshino K et al.; Transmission of Streptococcus pneumoniae between children and their parents was evaluated in 29 pairs from 25 families . The serotypes of 35 pneumococcal isolates from 18 (62.1%) of 29 child-parent pairs were identical . Of the 35 isolates, 23 showed intermediate resistance and 10 were fully resistant to penicillin G . PCR indicated that all 35 strains had at least one alteration in penicillin-binding protein genes pbp1a, pbp2x, and pbp2b and 33 strains had macrolide resistance genes mef(A) and/or erm(B) . As a result, the PCR patterns of 16 of 18 pairs were identical . Molecular typing by pulsed-field gel electrophoresis showed that 12 pairs were indistinguishable, 3 pairs were closely related, 2 pairs were possibly related, and only one pair was different . Our data indicate the presence of a high rate of transmission of penicillin-resistant S . pneumoniae between children and their parents.

J Clin Microbiol, 2002 Nov, 40(11), 4332 - 3
Impact of modified nonmeningeal Streptococcus pneumoniae interpretive criteria (NCCLS M100-S12) on the susceptibility patterns of five parenteral cephalosporins: report from the SENTRY antimicrobial surveillance program (1997 to 2001); Jones RN et al.; The revised interpretive criteria for Streptococcus pneumoniae recently published in the NCCLS M100-S12 informational supplement provide two sets of breakpoints for some cephalosporins: one set for meningeal infection isolates and a new set for nonmeningeal infection isolates . The net effect of these changes was to increase the reported rates of susceptibility of S . pneumoniae to the more active parenteral cephalosporins, such as cefepime, cefotaxime, and ceftriaxone, by 9.1 to 13.0%, bringing their in vitro rates much closer to those of amoxicillin (modified in an earlier NCCLS publication) . These revised breakpoints will assist the rational prescribing of antimicrobial agents for the treatment of pneumococcal infections for specific types of infection and establish a greater correlation with clinical outcomes.

J Clin Microbiol, 2002 Nov, 40(11), 4329 - 31
Evaluation of methods to increase the sensitivity and timeliness of detection of Streptococcus agalactiae in pregnant women; Overman SB et al.; Direct culture of rectovaginal specimens on Granada agar was compared to culture on sheep blood agar plate (SBAP) and AccuProbe detection of group B streptococcus from overnight LIM broth enhancement cultures (LIM-SBAP) . Both broth-enhanced methods demonstrated excellent sensitivity (97.5% for LIM-SBAP and 93.5% for AccuProbe), while Granada agar demonstrated a sensitivity of only 40.3%.

J Clin Microbiol, 2002 Nov, 40(11), 3942 - 50
Dissemination of Streptococcus pneumoniae clone Colombia(5)-19 in Latin America; Gamboa L et al.; Streptococcus pneumoniae serotype 5 is the third most common capsular type causing invasive diseases in children younger than 5 years in Latin America . Preliminary data on Colombian serotype 5 isolates indicated a common clonal origin associated with resistance to tetracycline (TET) and chloramphenicol (CHL) . We studied 172 S . pneumoniae serotype 5 invasive isolates from Argentina, Brazil, Colombia, Guatemala, Mexico, and Uruguay and confirmed the presence of the Colombia(5)-19 clone throughout Latin America . Fifteen subtypes of a pulsed-field gel electrophoresis pattern and 4 electrophoretic types (ET) were obtained . Most of the isolates from different geographical regions belonged to pattern A (34.3%), subtype A5 (41.9%), and ET1 (91.1%) . The A pattern (n = 59) was resistant to TET and had variable resistance to CHL; it was present in Brazil (10.2%), Colombia (78%), Guatemala (8.5%), and Mexico (3.4%) . Subtype A5 with variable susceptibility to TET and sensitive to CHL was found in Argentina (29.2%), Mexico (8.3%), and Uruguay (62.5%) . Subtypes A1-A4, A7-A8, and A9-A11 (closely related to A) also shared ET1, while subtype A6 was assigned to ET1, ET2, and ET3 . Eleven subtypes (n = 21) were found to be specific for one country each . In summary, the S . pneumoniae serotype 5 isolates from Latin American are genetically closely related but show different patterns of antibiotic resistance, probably as a result of horizontal transfer.

J Pharm Biomed Anal, 2002 Nov 7, 30(4), 961 - 8
Determination of moxifloxacin in human plasma by liquid chromatography electrospray ionization tandem mass spectrometry; Vishwanathan K et al.; Moxifloxacin is an advanced-generation, 8-methoxy fluoroquinolone that is active against a broad spectrum of pathogens, including antibiotic resistant Streptococcus pneumoniae . Development of a rapid, sensitive and selective method for the determination of moxifloxacin in human plasma is essential for understanding the pharmacokinetics of the drug when administered orally or intravenously . Solid phase extraction (SPE) using Oasis(R) HLB was used to extract moxifloxacin and the internal standard lomefloxacin from plasma . A method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was developed and validated to quantitate moxifloxacin in human plasma . The precursor and major product ion of the analyte was monitored on a triple quadrupole mass spectrometer with positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode . Mechanisms for the formation of collision-induced dissociation (CID) products of moxifloxacin are proposed . Linear calibration curves were generated from 1 to 1000 ng/ml with coefficients of determination greater than 0.999 . The inter-day and intra-day precision (% CV) was less than 11.3% and accuracy (% error) was less than 10.0% for moxifloxacin . The limit of detection (LOD) for the method was 50 pg/ml based on a signal to noise ratio of 3.

Curr Treat Options Gastroenterol, 2002 Dec, 5(6), 479 - 489
Spontaneous Bacterial Peritonitis; Hillebrand DJ; Spontaneous bacterial peritonitis (SBP) is the prototypical ascitic fluid infection occurring in patients with advanced liver disease and ascites . The key to successful treatment of SBP is a knowledge of appropriate antibiotic regimens and an understanding of the setting in which infection develops, particularly those individuals at high risk for infection . A high index of suspicion should lead to early diagnostic paracentesis and ascitic fluid analysis . Treatment of SBP involves the use of non-nephrotoxic broad-spectrum antibiotics expected to cover the typical bacterial flora associated with SBP . SBP typically involves infection with a single organism, with Escherichia coli, Klebsiella spp, and Streptococcus spp responsible for nearly three fourths of cases . The treatment of choice is cefotaxime 2 g given intravenously every 8 hours for a total of 5 days . The antibiotic regimen is adjusted based on the results of ascitic fluid cultures . Other antibiotic regimens for SBP are less well studied . Given the significant morbidity and mortality rates associated with SBP, efforts to prevent its development and recurrence with antibiotic prophylaxis are warranted . The most extensively studied form of prophylaxis involves selective intestinal decontamination (SID) with the oral fluoroquinolone norfloxacin . Individuals with low-protein ascites (ascitic fluid total protein < 1g/dL) benefit from SID with norfloxacin 400 mg daily during times of hospitalization . Long-term primary prophylaxis during outpatient management of individuals awaiting liver transplantation with severe ascites and advanced liver failure should also be considered . Patients with cirrhosis and upper gastrointestinal bleeding should receive norfloxacin 400 mg twice daily for 1 week following their bleed . Those individuals surviving an episode of SBP should be treated with norfloxacin 400 mg daily until the risk of SBP is removed by definitive resolution of the ascites or liver transplantation surgery . Although the infection-related mortality associated with SBP has decreased to less than 10%, hospitalization-related mortality remains as high as 30% as a result of the severe underlying liver disease in which the infection arises and the marked generation of cytokines and nitric oxide resulting from the infection . Recently, the simultaneous administration of intravenous albumin and antibiotics for SBP has been shown to result in the decreased development of azotemia and hospitalization-related mortality . Further improvement in the outcomes of SBP will require treatments targeting this cytokine cascade rather than the development of more potent antibiotics.

J Antimicrob Chemother, 2002 Nov, 50(5), 665 - 72
Virulence factor expression by Gram-positive cocci exposed to subinhibitory concentrations of linezolid; Gemmell CG et al.; Linezolid is a new oxazolidinone with potent antibacterial activity against Gram-positive cocci; it uniquely inhibits bacterial translation through inhibition of 70S initiation complex formation . The effects of sub-growth-inhibitory concentrations of linezolid on the expression of various structural and soluble virulence factors of Staphylococcus aureus and Streptococcus pyogenes were examined . For S . aureus, strains Wood 46 and Cowan 1 (NCTC 8532) were used to measure protein A, coagulase, alpha-haemolysin (hla) and delta-haemolysin (hld) . For S . pyogenes, strain NCTC 9994 was used to measure M protein, streptolysin O (SLO) and DNase . Coagulase was assayed by clotting of citrated rabbit plasma, and hla, hld and SLO by lysis of rabbit, human and horse erythrocytes, respectively . Protein A and M protein were measured indirectly using bacterial susceptibility to phagocytic ingestion of radiolabelled bacteria by human neutrophils . When S . aureus was grown in 1/2, 1/4 and 1/8 MIC, linezolid, coagulase, hla and hld production were impaired . Susceptibility to phagocytosis was changed by growth in the presence of 1/2 MIC linezolid compared with that in its absence (50.8 +/- 4.1% versus 38.9 +/- 2.9%; P <or= 0.05) . When S . pyogenes was grown in 1/2, 1/4 and 1/8 MIC linezolid, SLO and DNase production were impaired compared with that of bacteria grown in the absence of the drug; its susceptibility to phagocytosis was also increased (52.8% bacteria ingested versus 37.5%; P <or= 0.05) . A reduction in virulence factor expression at sub-MIC linezolid concentrations may be of benefit in the treatment of Gram-positive infections.

J Dent Res, 2002 Nov, 81(11), 784 - 7
A DNA vaccine encoding a cell-surface protein antigen of Streptococcus mutans protects gnotobiotic rats from caries; Fan MW et al.; A cell-surface protein antigen (PAc) of Streptococcus mutans is considered a virulence factor because it may mediate initial attachment of Streptococcus mutans to tooth surfaces . Thus, inhibiting PAc is predicted to provide protection against caries . To develop vaccines against dental caries, we constructed a DNA vaccine, pCIA-P, which encodes two high-conservative regions of PAc . Expression of the recombinant protein was obtained in eukaryotic cells in vitro and in vivo . In this report, we provide evidence that fewer caries lesions, and high levels of PAc-specific salivary IgA antibody and serum IgG antibody, were observed in gnotobiotic rats following targeted salivary gland (TSG) administration of pCIA-P . This study shows that the recombinant DNA vaccine pCIA-P could induce protective anti-caries immune responses and that TSG immunization is a promising strategy for the inhibition of dental caries.

CMAJ, 2002 Oct 15, 167(8), 885 - 91
Antimicrobial resistance in Canada; Conly J; Antibiotic resistance has increased rapidly during the last decade, creating a serious threat to the treatment of infectious diseases . Canada is no exception to this worldwide phenomenon . Data from the Canadian Nosocomial Infection Surveillance Program have revealed that the incidence of methicillin-resistant Staphylococcus aureus, as a proportion of S . aureus isolates, increased from 1% in 1995 to 8% by the end of 2000, and vancomycin-resistant enterococcus has been documented in all 10 provinces since the first reported outbreak in 1995 . The prevalence of nonsusceptible Streptococcus pneumoniae in Canada in 2000 was found to be 12% . Human antimicrobial prescriptions, adjusted for differences in the population, declined 11% based on the total number of prescriptions dispensed between 1995 and 2000 . There was also a 21% decrease in beta-lactam prescriptions during this same period . These data suggest that systematic efforts to reduce unnecessary prescribing of antimicrobials to outpatients in Canada, beginning after a national consensus conference in 1997, may be having an impact . There is, however, still a need for continued concerted efforts on a national, provincial and regional level to quell the rising tide of antibiotic resistance.

Am J Respir Crit Care Med, 2003 Jan 15, 167(2), 171 - 9 Epub 2002 Sep 25.
Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia; Knapp S et al.; Alveolar macrophages (AMs) are considered major effector cells in host defense against respiratory tract infections by virtue of their potent phagocytic properties . In addition, AMs may regulate the host inflammatory response to infection by production of cytokines and by their capacity to phagocytose apoptotic polymorphonuclear cells (PMNs) . To elucidate the in vivo contribution of AM to host defense against pneumococcal pneumonia, we depleted mice of AMs via pulmonary application of liposomal dichloromethylene-bisphosphonate (AM- mice) before inoculation with Streptococcus pneumoniae; control mice received saline (AM+sal) or liposomal phosphate-buffered saline (AM+lip) before bacterial inoculation . AM- mice displayed a significantly higher mortality compared with AM+ control mice, whereas bacterial clearance did not differ . Poor outcome of AM- mice was accompanied by a pronounced increase of local proinflammatory cytokine production as well as strongly elevated and prolonged pulmonary PMN accumulation . Closer examination of infiltrating PMN in AM- mice disclosed high proportions of apoptotic and secondary necrotic cells, reflecting the lack of efficient clearance mechanisms in the absence of AMs . Furthermore, caspase-3 staining showed only slightly higher activity in AM- mice, arguing against accelerated apoptosis per se . These data suggest that AMs are indispensable in the host response to pneumococcal pneumonia by means of their capacity to modulate inflammation, possibly via elimination of apoptotic PMNs.

Mol Microbiol, 2002 Oct, 46(2), 557 - 69
A fibrinogen receptor from group B Streptococcus interacts with fibrinogen by repetitive units with novel ligand binding sites; Schubert A et al.; Group B Streptococcus (GBS) is a frequent cause of bacterial sepsis and meningitis in neonates . During the course of infection, GBS colonizes and invades a number of host compartments, thereby interacting with different host proteins . In the present report, we describe the isolation of the fbsA gene, which encodes a fibrinogen receptor from GBS . The deduced FbsA protein is characterized by repetitive units, each 16 amino acids in length . Sequencing of the fbsA gene from five different GBS strains revealed significant variation in the number of repeat-encoding units . The deletion of the fbsA gene in the genome of GBS 6313 completely abolished fibrinogen binding, suggesting that FbsA is the major fibrinogen receptor in this strain . Growth of the fbsA deletion mutant in human blood was significantly impaired, indicating that FbsA protects GBS from opsonophagocytosis . In Western blot experiments with truncated FbsA -proteins, the repeat region of FbsA was identified as mediating fibrinogen binding . Using synthetic peptides, even a single repeat unit of FbsA was demonstrated to bind to fibrinogen . Spot membrane analysis and competitive binding experiments with peptides carrying single amino acid substitutions allowed the prediction of a fibrinogen-binding motif with the consensus sequence G-N/S/T-V-L-A/E/M/Q-R-R-X-K/R/W-A/D/E/N/Q-A/F/I/L/V/Y-X-X-K/R-X-X.

J Infect Dis, 2002 Nov 15, 186(10), 1518 - 21 Epub 2002 Oct 25.
Synergistic action of nitric oxide release from murine macrophages caused by group B streptococcal cell wall and beta-hemolysin/cytolysin; Ring A et al.; Group B streptococcus (GBS) is the leading cause of sepsis in neonates . Nitric oxide (NO) release plays a role in the hypotension that characterizes septic shock . It has been shown that GBS beta-hemolysin/cytolysin (beta-h/c) stimulates the transcription of inducible NO synthase (iNOS) in murine macrophages via intracellular pathways similar to those that mediate lipopolysaccharide-induced iNOS activation . Here, it is demonstrated that the GBS cell wall and beta-h/c act synergistically to induce iNOS in interferon (IFN)-gamma-primed {corrected} RAW 264.7 murine macrophages . In nonprimed macrophages, combined activation by the GBS cell wall plus beta-h/c is necessary to induce an NO response, which indicates that both virulence factors cooperate to substitute for the priming signal typically provided by IFN-gamma {corrected}.

J Infect Dis, 2002 Nov 15, 186(10), 1422 - 9 Epub 2002 Oct 23.
Induction of functional secretory IgA responses in breast milk, by pneumococcal capsular polysaccharides; Finn A et al.; Capsule-specific secretory IgA (s-IgA) in breast milk may enhance protection against pneumococcal disease in infants . After immunization of 3 lactating mothers with 23-valent polysaccharide vaccine, specific s-IgA, but not IgG, increased by >2-fold in milk of at least 1 subject for 6 of 7 serotypes . The s-IgA was predominantly IgA1, in secretory form, and highly specific with avidity distinct from serum IgA and IgG . Milk whey from 2 immunized women supported dose- and complement-dependent killing of Streptococcus pneumoniae serotypes 19F and 14 by human neutrophils, as did purified s-IgA to serotype 19F . These data reveal that capsule-specific human s-IgA in breast milk can initiate killing of S . pneumoniae, providing proof of concept that vaccine-induced human mucosal s-IgA can support functional bactericidal activity . Determining the biologic role for s-IgA in killing and inhibiting adherence of S . pneumoniae in vivo will contribute to the development of mucosal vaccines against S . pneumoniae.

Immunol Res, 2002, 26(1-3), 223 - 34
Microbial/host interactions: mechanisms involved in host responses to microbial antigens; Michalek SM et al.; The indigenous oral microflora and the host are normally in a state of equilibrium; however, the introduction of a pathogen can result in innate and adaptive immune responses that either contribute to the development of the disease or lead to host immunity . The interactions between the microorganisms and the host are very dynamic, thus allowing the complex interplay between host molecules and bacterial antigens . In this article, we focus on the mechanisms involved in the pathogenesis of and host responses to two oral pathogens: the Gram-negative bacterium Porphyromonas gingivalis, implicated in the etiology of periodontal disease, and the Gram-positive Streptococcus mutans, a primary agent involved in dental caries formation . Furthermore, we address mechanisms involved in the ability of select adjuvants and delivery systems to potentiate mucosal and systemic immune responses to microbial vaccine antigens.

Aust N Z J Obstet Gynaecol, 2002 Oct, 42(4), 362 - 4
Early-onset group B streptococcus prevention protocols in New Zealand public hospitals; Gosling IA et al.; OBJECTIVE: Determine group B streptococcus (GBS) prevention protocols . METHODS: Questionnaire survey of 19 hospitals accounting for 73% of New Zealand births . RESULTS: Prevention policies were reported by 16 (84%) hospitals (bacteriological-screening n = 4, risk-factor determination n = 8, both strategies n = 4) . Only five out of 12 (42%) centres using risk-assessment administered antibiotics for all high-risk criteria . Inadequate specimen collection and culture methods meant no hospital maximised culture-based strategies . Nevertheless, hospitals with prevention policies had lower early-onset GBS disease rates (0.46 versus 1.44 per 1,000 births; OR 0.32; (95% CI 0.12, 0.98)) . CONCLUSIONS: Prevention strategies can be further improved by hospitals fully implementing nationally agreed guidelines.

J Infect Dis, 2002 Nov 1, 186(9), 1253 - 60 Epub 2002 Oct 03.
Choline-binding protein A of Streptococcus pneumoniae elicits chemokine production and expression of intercellular adhesion molecule 1 (CD54) by human alveolar epithelial cells; Murdoch C et al.; Recruitment of neutrophils into alveolar air spaces is an early event in the pathogenesis of pneumonia due to Streptococcus pneumoniae . This results from chemokines released by activated endothelial and epithelial cells and alveolar macrophages . Culture supernatants of 6 wild-type strains of S . pneumoniae, shown to contain choline-binding protein A (CbpA; clades A and B), induced release of chemokine CXCL8 from the human alveolar epithelial cell line A549, whereas a CbpA deletion mutant elicited significantly reduced CXCL8 release, compared with that of its isogenic parent (P<.01) . Recombinant CbpA up-regulated expression of messenger RNA of CXCL8 and CCL2 but not of XCL1, CXCL10, CCL1, CCL3, CCL4, or CCL5 in A549 cells and induced increased secretion of CXCL8, CCL2, CXCL1, and CXCL5 in a dose- and time-dependent manner . CbpA also increased the expression of intercellular adhesion molecule 1 (CD54) by A549 cells . Thus, CbpA of S . pneumoniae induces the transcription and release of proinflammatory molecules by human alveolar epithelial cells.

Eur J Paediatr Neurol, 2002, 6(6), 327 - 9
Multiphasic disseminated encephalomyelitis associated with streptococcal infection; Hartel C et al.; Multiphasic disseminated encephalomyelitis (MDEM) is a rare peculiar diagnosis which is defined as acute demyelinating central nervous system disease with relapses occurring only within 4 weeks of initial manifestation . This report describes the case of a 6-year-old boy with MDEM diagnosed by clinical findings and magnetic resonance imaging . The disease had a biphasic evolution, and with a second course of high-dose corticosteroids a complete recovery without further relapse was obtained during the following 18 months . Serological evidence of streptococcal infection as specific trigger for MDEM was given . Thus this report raises the question whether an additional penicillin prophylaxis could be valuable for prevention of streptococcus-associated MDEM relapses.

Semin Neonatol, 2002 Aug, 7(4), 315 - 23
Vaccines to prevent neonatal GBS infection; Paoletti LC et al.; Group B Streptococcus (GBS) remains the leading bacterial cause of neonatal sepsis and meningitis in the United States . Although antibiotic prophylaxis has decreased the infection rate, the best long-term solution lies in the development of effective vaccines . The GBS capsular polysaccharide (CPS) is a major target of antibody-mediated immunity . While antibody to CPS is protective, uncoupled CPS is variably immunogenic in humans, a finding that led to the development of GBS CPS-protein conjugate vaccines . GBS CPS-protein conjugate vaccines of all clinically important serotypes have been produced and tested in animals . Mice and baboons immunized with CPS conjugates transplacentally transferred functionally active GBS-specific IgG to their offspring . Phase 1 and phase 2 clinical trials have shown that GBS conjugate vaccines are safe, well-tolerated and immunogenic in healthy adults . Moreover, human antibodies elicited by the conjugate vaccines are functionally active both in vitro and in animal models of invasive GBS disease .

Semin Neonatol, 2002 Aug, 7(4), 259 - 74
Infection and prematurity and the role of preventive strategies; Romero R et al.; This article reviews the role of infection in spontaneous premature parturition, the pathways of ascending intrauterine infection, microbiology, and the frequency of intra-amniotic infection in obstetrical complications leading to premature delivery . The evidence that infection is causally linked to premature birth is critically examined, as is the relationship between urogenital tract infection/colonization with microorganisms and the risk of preterm birth . The effect of antibiotic administration in perinatal outcome in patients with preterm labor and intact membranes, preterm premature rupture of membranes, asymptomatic bacteriuria, Group B streptococcus and genital mycoplasmas of the lower genital tract, and bacterial vaginosis are critically examined.

J Microbiol Methods, 2003 Jan, 52(1), 69 - 73
Quantitative determination of pneumococcal capsular polysaccharide serotype 14 using a modification of phenol-sulfuric acid method; Cuesta G et al.; The capsular polysaccharide of Streptococcus pneumoniae, serotype 14, is part of every pneumococcal vaccine presently in the market or under development . A strategy for the quantitative determination of this polysaccharide by the phenol-sulfuric acid method is described . The modality of acid addition is shown to be the critical step for obtaining reproducible test results between different technicians . Raising the incubation temperature above 80 degrees C increased the consistency of the method by more than 60% regardless of the acid addition modality, but at the expense of some loss of sensitivity . Incubation at 110 degrees C was found necessary to obtain reproducible results within 3% for this technique, which was used to follow the enrichment of the polysaccharide during the last steps of purification . A model mixture of the component polysaccharide sugars provided an adequate and economic standard to construct the calibration curve for this assay, with absorbance reading either in the reaction tubes or in a microplate . A similar procedure may be applied to the determination of other bacterial polysaccharides as well.

Nippon Jibiinkoka Gakkai Kaiho, 2002 Sep, 105(9), 925 - 30
{Bacterial examination of sinusitis using antral puncture and irrigation}; Adachi M et al.; Aerobic bacterial examination for sinusitis was conducted using specimens from maxillary sinuses collected by antral puncture in 540 patients--284 men and 256 women aged 6-89 years--between May 1999 and April 2000 . We obtained 528 strains of bacteria . Our results were as follows: 1 . We obtained 303 pathogens from 540 patients . In acute sinusitis, the most frequently found was Streptococcus pneumoniae (30.4%), followed by Hemophilus influenzae (27.7%) . In chronic cases, the most frequently found was Streptococcus pneumoniae (16.0%), followed by Hemophilus influenzae (15.1%) and Staphylococcus epidermidis (12.6%) . 2 . We found an increase in bacteria resistant to multiple drugs, with 11.1% of the Staphylococcus aureus isolates methicillin-resistant in acute sinusitis and 40% methicillin-resistant in chronic sinusitis, and that 30.6% of Streptococcus pneumoniae isolates were penicillin-resistant . 3 . Ciclacillin was effective against 64.7% of all pathogens isolated in this study, cefpodoxime proxetil effective against 6.5%, and cefixime effective against 2.4% . 4 . In considering pathogens, we therefore choose antibiotics and make a maxillary aspiration puncture.

Pediatr Cardiol, 2003 Mar-Apr, 24(2), 161 - 3 Epub 2002 Oct 29.
Endocarditis due to Streptococcus acidominimus; Brachlow A et al.; It has been reported in recent years that the causative microorganisms, affected population, and clinical presentation of infective endocarditis have changed . We report on a 15-year-old boy with ventricular septal defect who was diagnosed with Streptococcus acidominimus endocarditis.

J Bacteriol, 2002 Nov, 184(22), 6384 - 6
Structural heterogeneity of the streptococcal C5a peptidase gene in Streptococcus pyogenes; Koroleva IV et al.; The 3' ends of the genes for the C-terminal region of C5a peptidase from 15 Streptococcus pyogenes isolates were analyzed by PCR . Amplicons were found to differ in size . DNA sequence analysis revealed that the differences between PCR fragment sizes accorded with the number of R repeats in the C5a peptidase gene.

J Bacteriol, 2002 Nov, 184(22), 6316 - 24
Postgenomic analysis of four novel antigens of group a streptococcus: growth phase-dependent gene transcription and human serologic response; Reid SD et al.; Analysis of three group A Streptococcus genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins . Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram-positive bacteria to the cell surface . Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo . However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains . Surface expression of two proteins was confirmed by flow cytometry . Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection . These results are additional evidence that postgenomic strategies provide new ways to identify and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research.

Vaccine, 2002 Nov 1, 20(31-32), 3764 - 9
Development of a new vaccine delivery method for fish: percutaneous administration by immersion with application of a multiple puncture instrument; Nakanishi T et al.; A new administration method was developed for vaccination of juvenile rainbow trout against beta-haemolytic Streptococcus . This simple and convenient method was equal in effectiveness to intra-peritoneal injection . Small skin lesions were produced using a multiple puncture instrument while fish were immersed in a vaccine suspension containing formalin-killed Streptococcus iniae . Upon challenge 2 weeks after vaccination, mortality of fish vaccinated by this method was 40%, equal to that by intra-peritoneal injection, while non-vaccinated control fish and fish vaccinated by immersion (without multiple puncture) each experienced 80% mortality . High efficacy was obtained with the multiple puncture/immersion method even when vaccine was diluted 10-fold . Quantitative analysis using fluorescent microspheres revealed that both antigen uptake by skin and delivery to the kidney and spleen were more effective with this method than with immersion alone . Microspheres were found in the skin within the pinpoint lesions and pressure mark caused by multiple puncture instrument . The greater protection gained by the present method can be attributed to higher numbers of particulate antigens taken up by fish and delivered to the lymphoid tissues.

Vaccine, 2002 Nov 1, 20(31-32), 3720 - 4
Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users; Amendola A et al.; The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls . The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART) . Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples.Vaccinations were well-tolerated . The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals . No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts . Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals . Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only . Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels . Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.

J Gastrointest Surg, 2002 Sep-Oct, 6(5), 723 - 9
Megaesophagus microbiota: a qualitative and quantitative analysis; Pajecki D et al.; Bacterial overgrowth in the esophageal lumen in patients with megaesophagus can be the cause of recurring pulmonary infections, infectious complications due to surgical or endoscopic procedures, and the development of dysplasia of the esophageal mucosa and cancer . Despite this, esophageal microbiota in the megaesophagus have never been studied . The aim of this study was to analyze qualitatively and quantitatively the microbiota in chagasic megaesophagus in comparison to the normal esophagus . Twenty-five patients (10 men and 15 women), ranging in age from 24 to 74 years (mean years), were prospectively studied from March to September 2000 . Fifteen patients with chagasic megaesophagus were divided into three subgroups (n = 5 patients in each) according to the grade of esophageal dilation: MG1 = megaesophagus grade I; MG2 = megaesophagus grade II; and MG3 = megaesophagus grade III . Another group of 10 patients without esophageal disease served as a control group . Samples were collected using a method especially developed to avoid contamination with microorganisms of the oral cavity and oropharynx . In the control group, 40% of the cultures were positive with the genus Streptococcus predominating and concentrations varying from 10(1) to 10(2) colony-forming units/ml . In the megaesophagus group, 93.3% of the cultures were positive, with great variability in the bacteria and a predominance of various aerobic gram-positive bacteria (Streptococcus was most common) and anaerobic bacteria (Veillonella was most frequent) in concentrations that ranged from 10(1) to 10(5) colony-forming units/ml . The bacterial concentrations were generally more elevated in MG3 patients in comparison to MG1 and MG2 patients and the control group (P < 0.05) . It was concluded that patients with megaesophagus have a variety of microbiota consisting mostly of aerobic gram-positive and anaerobic bacteria, in concentrations that varied according to the degree of esophageal dilation .

Am J Respir Cell Mol Biol, 2002 Nov, 27(5), 611 - 8
Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles; Becker S et al.; Inhalation of particulate matter (PM) may result in exacerbation of inflammatory airways disease, including asthma . Results from this laboratory have shown that the coarse inhalable particle fraction (PM(2.5-10)) is responsible for most of the PM effects on human airway macrophages (AM), including induction of cytokine production . Endotoxins associated with these particles account for a large part of their potency, as activity of PM can be inhibited by polymixin B and an activating moiety bound by lipopolysaccharide (LPS)-binding protein (LBP) . The hypothesis behind the present study was that not only particle-bound LPS, but also Gram-negative (Gram-) and Gram-positive (Gram+) bacteria are responsible for PM-induced stimulation of AM, and therefore that PM are likely to activate receptors involved in recognition of microbes . Low level contamination of model pollution particles with environmental Staphyloccocus, Streptococcus, and Pseudomonas species was found to confer cytokine-inducing activity on inactive particles . Only one Gram- bacterium was sufficient for significant stimulatation of 100 AM, whereas at least three times more Gram+ bacteria were required for a similar level of response . Cytokine responses induced by PM as well as Gram+ and Gram- bacteria were inhibited by anti-CD14 antibody and required the presence of LBP-containing serum . The involvement of Toll-like receptor (TLR) 2 and 4 in recognition of PM(2.5-10) was investigated in transfected Chinese hamster ovary cells expressing CD14 and TLR2 or TLR4 . TLR4 was found to be involved in PM(2.5-10) and Pseudomonas-induced activation, whereas TLR2 activation was induced by both Gram+ and Gram- bacteria and by PM . The synthetic lipid A analog E5531 fully inhibited the response to purified LPS and partially inhibited the response to PM and PSEUDOMONAS: In contrast, E5531 had no effect on the response to STAPHYLOCOCCUS: Taken together, these results implicate microbial components as important players in AM-dependent inflammatory responses to PM.

Transplantation, 2002 Oct 15, 74(7), 1048 - 50
Streptococcus pneumoniae mycotic aortic aneurysm after allogeneic bone marrow transplantation; Rabitsch W et al.; BACKGROUND: Streptococcus pneumoniae (SP) is a common cause of community-acquired pneumonia and accounts for up to 30% of all cases of pneumonia . Patients with chronic graft-versus-host-disease (GvHD) after allogeneic bone marrow transplantation (BMT) have a high susceptibility to SP infections . So far, mycotic aneurysm resulting from SP has not been reported after BMT . METHODS: We report on a patient with extensive, chronic GvHD who developed low back pain 22 months after allogeneic BMT . RESULTS: Computed tomography of the abdomen displayed mycotic, saccular aneurysmatic enlargement of the infrarenal aorta, with leakage of contrast medium into the aneurysm . The aneurysm was resected, and the defect was closed with an autologous patch from the internal iliac artery . Bacteriologic samples from the abscess grew SP . The patient recovered uneventfully . CONCLUSIONS: This observation confirms the importance of pneumococcal prophylaxis after BMT and suggests that an aggressive diagnostic approach should always be considered in patients with chronic GvHD, even if they present with nonspecific symptoms.

Pediatr Infect Dis J, 2002 Oct, 21(10), 922 - 7
Comparison of two rapid Streptococcus pyogenes diagnostic tests with a rigorous culture standard; Gieseker KE et al.; BACKGROUND: Comparisons of rapid antigen tests for the diagnosis of pharyngitis are often made between published studies but may not be reliable given differences in study design, sampling and reference standard definitions . Tests are rarely compared against each other in a single study . METHODS: The sensitivity and specificity of two rapid diagnostic tests were compared against a multiplate culture standard defined as the identification of on any of four culture plates . Paired swabs were tested for antigen using Genzyme's OSOM Ultra Strep A Test and compared with Biostar's Strep A OIA Max Test . RESULTS: Ninety-four (31.1%) of 302 matched samples were identified with The sensitivity of Genzyme's OSOM Ultra Strep A Test against the multiplate culture standard was 92.6%, significantly higher ( P= 0.001) than that (75.5%) of Biostar's Strep A OIA Max Test . Specificities were 92.8 and 97.1%, respectively . Data analysis of culture results and statistical modeling showed that cultures of two or more samples are necessary for a sensitivity of 95% or greater for a comparison standard compared with true disease status . CONCLUSIONS: When comparing the performance of rapid antigen tests for pharyngitis, a rigorous culture standard should be used consisting of at least two separate samples (swabs and/or pledgets), ultimately plated on selective agar . Genzyme's OSOM Ultra Strep A Test was significantly more sensitive than Biostar's Strep A OIA Max Test in comparison with a multiplate culture standard and a same swab, single plate culture standard.

Pediatr Infect Dis J, 2002 Oct, 21(10), 903 - 10
Outcome of penicillin-nonsusceptible Streptococcus pneumoniae meningitis: a nested case-control study; Kellner JD et al.; BACKGROUND: There are few data comparing the clinical features, management and outcome of penicillin-nonsusceptible (PNSP) meningitis patients with penicillin-susceptible (PSSP) meningitis patients . METHODS: We performed a retrospective, nested case-control study comparing cases with PNSP meningitis with controls with PSSP meningitis obtained from the Immunization Monitoring Program, Active (IMPACT) cross-Canada surveillance study of invasive infections . RESULTS: There were 30 PNSP meningitis cases (10.1% of total) and 45 PSSP meningitis controls from 6 centers obtained from 297 meningitis cases in the IMPACT database from 1991 through 1999 . Vancomycin was used for empiric therapy in no cases and controls in 1991 to 1993 and in all cases in 1999 . A third generation cephalosporin was used in 93.3% of confirmed PNSP cases, and 70.0% also received vancomycin and/or rifampin . Penicillin was used in 66.7% of confirmed PSSP cases . PNSP cases were more likely than PSSP controls to have a second lumbar puncture (odds ratio, 4.1; P= 0.01) . PNSP cases were treated with intravenous antibiotics for an average of 15.6 days compared with 12.3 days for controls ( P= 0.04) . Among PNSP cases, those patients who did not receive empiric vancomycin were treated with intravenous antibiotics for an average of 18.5 days compared with 12.0 days for those who did receive empiric vancomycin ( P= 0.04) . The overall mortality was 5.3%, and 36.6% of survivors had >or=1 neurologic sequelae, including 19.7% with hearing loss . In multivariate statistical models, PNSP was not a risk factor for intensive care unit admission or neurologic sequelae . CONCLUSIONS: Management of suspected bacterial meningitis and confirmed meningitis in Canadian children changed in the past decade . Treatment of PNSP meningitis is significantly different from that for PSSP meningitis . These changes have occurred in response to the emergence of PNSP in Canada . Neurologic sequelae remain common after meningitis, but there are no differences between PNSP cases and PSSP cases.

Blood, 2003 Feb 1, 101(3), 831 - 6 Epub 2002 Sep 19.
Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation; Molrine DC et al.; Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, impaired antibody responses to pneumococcal polysaccharide vaccines . We examined whether donor immunization with a heptavalent pneumococcal conjugate vaccine (PCV7) would elicit protective antibody responses to additional doses of vaccine administered early after transplantation . Ninety-six patients scheduled to receive an allogeneic hematopoietic cell transplant were randomized with their donors to receive either a dose of PCV7 vaccine or no vaccine before transplantation . All patients received PCV7 at 3 months, 6 months, and 12 months following transplantation, and serotype-specific antibody concentrations were determined after each dose . Following HCT, geometric mean antibody concentrations of patients in the immunized donor group were significantly higher for 5 of the 7 vaccine serotypes after one dose (P <.05) and for 4 of the 7 serotypes after 2 doses of vaccine (P <.03) . Sixty-seven percent of patients in the immunized donor group had presumed protective IgG concentrations more than or equal to 0.50 microg/mL to all 7 serotypes following the first dose of vaccine compared to 36% in the unimmunized donor group (P =.05) . After the third dose of vaccine, both groups had more than 60% of patients with concentrations at least 0.50 microg/mL to all vaccine serotypes . Donor immunization enhances early antibody responses of patients undergoing HCT to pneumococcal conjugate vaccine . A 3-dose schedule of PCV7 vaccine at 3, 6, and 12 months is immunogenic in these patients regardless of donor immunization.

Int J Pediatr Otorhinolaryngol, 2002 Nov 11, 66(2), 143 - 8
Acute mastoiditis: a 10 year retrospective study; Tarantino V et al.; This retrospective study reviews our experience in the management of acute otomastoiditis over 10 years . During the study period we identified 40 cases in children aged 3 months-15 years with a peak incidence in the second year of life . Sixty per cent of them had a history of acute otitis media (AOM) . All the children were already receiving oral antibiotic therapy . Otalgia, fever, poor feeding and vomiting were the most common symptoms, all the children had evidence of retroauricolar inflammation . Computerized tomography (CT) and magnetic resonance imaging (MRI) were used to support the diagnosis and to evaluate possible complications . Streptococcus pneumoniae was the most common isolated bacterium . All the patients received intravenous antibiotics, 65% of children received only medical treatment, 35% also underwent surgical intervention . Mean length of hospital stay was 12.3 days . Cholesteathoma was diagnosed in one child . We conclude from our study that acute otomastoiditis is a disease mainly affecting young children, that develops from AOM resistant to oral antibiotics . Adequate initial management always requires intravenous antibiotics, conservative surgical treatment with miryngotomy is appropriate in children not responding within 48 h from beginning of therapy . Mastoidectomy should be performed in all the patients with acute coalescent mastoiditis or in case of evidence of intracranial complications .

FEMS Microbiol Lett, 2002 Sep 24, 215(1), 133 - 8
Functional characterization of domains found within a lytic enzyme produced by Streptococcus equi subsp . zooepidemicus; Lai AC et al.; Zoocin A is a lysostaphin-like streptococcolytic enzyme produced by Streptococcus equi subsp . zooepidemicus 4881 that specifically targets the cell walls of some closely related species . On the basis of sequence homology it was suggested that zoocin A was a domain-structured enzyme with the N-terminal domain responsible for catalysis (CAT) and the C-terminal domain for target recognition (SBD) . Polypeptides corresponding to zoocin A (rZooA) and each of the putative domains (rCAT and rSBD) were prepared by use of recombinant technology . The biological activities of each was compared by use of a dye-release assay and a cell-binding assay . Cell wall hydrolysis was shown to be a function of CAT and target recognition a function of the SBD . Expression of the zoocin A immunity factor gene produced cell walls resistant to hydrolysis by either rZooA or its component domains, and with reduced capacity to bind rZooA and rSBD.

An Esp Pediatr, 2002 Oct, 57(4), 310 - 6
{Predictive factors for invasive pnuemococcal disease: a case-control study}; Perez Mendez C et al.; BACKGROUND: Streptococcus pneumoniae causes significant morbidity in children, but data on the incidence of invasive pneumococcal disease in Spain are scarce . The objectives of this study were: 1) to describe the clinical and epidemiological features of invasive pneumococcal disease in our health district and 2) to determine factors predictive of invasive pneumococcal disease in febrile children seen at a hospital Emergency Department . MATERIAL AND METHODS: Design . Observational, retrospective, case-control study, from 1 October, 1992 to 31 March, 2001 . Location: Community Hospital in the north of Spain . Entry criteria for cases: febrile children under 14 years of age, seen at the Emergency Department during the study period, with growth of S . pneumoniae in the blood culture . Eligibility criteria for controls: febrile children under the age of 14 years seen at the Emergency Department during the study period with no bacterial growth in the blood culture . The first eligible child seen after each case was included as a control . Statistical analysis: descriptive analysis of patients with invasive pneumococcal disease and univariate analysis of each variable in relation to the dependent variable (blood culture positive for S . pneumoniae); multivariate analysis was performed using logistic regression techniques . RESULTS: Seventy-six cases of invasive pneumococcal disease were studied . The mean incidence of invasive pneumococcal disease (cases/100,000 children/year) was 174.1 for children under 24 months of age, 38.9 for children aged 24-59 months, and 5.9 for children older than 59 months . The incidence of pneumococcal meningitis in children under 24 months of age was 14.8 cases/100,000 children/ year . The most common diagnoses were occult bacteremia (64.5 %), pneumonia (17.1 %), and meningitis (9.2 %) . Mortality was 1.3 % . A total of 56.5 % of the S . pneumoniae strains showed penicillin resistance (11.8 % high-grade resistance) and 12.2 % showed cefotaxime resistance . Predictive factors for invasive pneumococcal disease were temperature greater than or equal to 39 degrees C (OR: 2.09; 95 % CI:91-4.79), generalized malaise (OR: 2.61; 95 % CI: 1.1-6.21), age between 6 and 36 months (OR: 4.06; 95 % CI: 1.79-9.21), and absolute neutrophil count (ANC) greater than or equal to 10,000 cells/mm3 (OR: 8.16; 95 % CI: 3.54-18.79) . CONCLUSIONS: 1 . The incidence of invasive pneumococcal disease in our health district is high and is greater than that reported for other European regions . 2 . In contrast, the incidence of pneumococcal meningitis is similar to that in other European countries . 3 . The most frequent diagnosis was occult bacteremia . 4 . In the case-control study, four variables showed significant independent association with the risk of invasive pneumococcal disease: temperature greater than or equal to 39 degrees C, general malaise, age between 6 and 36 months, and an ANC greater than or equal to 10,000 cells/mm3 . The most powerful predictor of invasive pneumococcal disease in our series was ANC.

An Esp Pediatr, 2002 Oct, 57(4), 301 - 9
{Study of the incidence of invasive pneumococcal disease in neonates and childre aged less than 5 years in the Basque country and Navarre (Spain)}; Bernaola Iturbe E et al.; BACKGROUND: Streptococcus pneumoniae is the most commonly reported bacterial cause of bacteremia and bacteremic pneumonia and the second most frequent cause of meningitis . OBJECTIVE: To establish the incidence, characteristics and serotypes causing invasive pneumococcal disease in children aged less than 5 years in two Autonomous Communities in Spain, the Basque country and Navarre, between 31 May 1988 and 1 June 2001 . PATIENTS AND METHODS: We performed a descriptive, observational and retrospective study . The study population was composed of children diagnosed with invasive pneumococcal disease in the public and private hospitals with a pediatrics departments . Invasive pneumococcal disease was defined as isolation of S . pneumoniae in blood, cerebrospinal fluid or any other sterile biological fluid . Medical records were reviewed and demographic and diagnostic variables were analyzed . Age-adjusted frequency rates were established for both regions using direct standardization . Confidence intervals were obtained by Poisson distribution . SPSS for Windows 10.0 and Epidat 2.1 were used for the analysis . Data were obtained from the 1999 municipal population census . RESULTS: One hundred seventy-one children aged 0-5 years were included . A total of 40.9 % (70 patients) were aged less than 12 months and 68.4 % were aged 0-2 years; 16.4 % had received drug therapy before diagnosis . The most common forms of presentation were occult bacteremia (45.6 %), bacteremic pneumonia (27.5 %) and meningitis (14.6 %) . The most frequent complications involved the respiratory tract, with pleural effusion in 23 % of cases of pneumonia . The standardized annual incidence rate of invasive pneumococcal disease (cases per 100,000) in children aged 0-59 months was 58.82 (95 % CI: 27.99-89.65) in Navarre and 55.35 (95 % CI: 38.81-71.88) in the Basque Country . In children aged 0-23 months, the overall incidence was 93.49 cases per 100,000 children (95 % CI: 77.32-112.04) and in infants aged 0-11 months, it was 110,21 cases per 100,000 children (95 % CI: 85.91-139.24) . The incidence rates for meningitis and bacteremia in children aged 0-23 months was 15.98 (95 % CI: 9.76-24.68) and 51.14 (95 % IC: 39.38-65.30) cases per 100.000 children . Fifty-nine strains were serotyped . The most frequent serotypes/groups were 1, 4, 6B, 14, 18C, 19 and 23F . A total of 52.15 % of the serotypes were penicillin-susceptible and 93 % were cefotaxime-susceptible . The serotypes/groups with the highest rates of resistance were 6B, 14,19, 23F and 35 . CONCLUSION: Our incidence rates are similar to those observed in other countries such as the United States and are higher than those reported for the rest of Europe . Vaccine coverage is similar to that described in other articles.

An Esp Pediatr, 2002 Oct, 57(4), 295 - 300
{Pneumococcal meningitis in Spanish children: incidence, serotypes and antibiotic resistance . Prospective and multicentre study}; Casado Flores J et al.; OBJECTIVE: To determine the incidence, as well as the implicated serotypes and patterns of antibiotic resistance of Streptococcus pneumoniae meningitis in Spanish children . MATERIAL AND METHOD: We performed a prospective, multicenter study in five Autonomous Communities (Catalonia, Galicia, Madrid, Navarre and the Basque Country) for 1 year (1 February 2000 31 January 2001) . All children aged 0-14 years with pneumococcal meningitis from all the hospitals in the Autonomous Communities studied were included . Diagnosis was based on clinical findings and isolation of S . pneumoniae in the cerebrospinal fluid/blood using routine methods or polymerase chain reaction . Serotyping was performed using the guellung reaction and/or immunoblotting and susceptibility to antibiotics was evaluated by the technique of agar dilution . The pediatric population aged 0-14 years in the Autonomous Communities studied comprises 2,290,304 children . RESULTS: Fifty-two cases were identified . One patient was aged less than 2 months old, 25 (48 %) were aged 2-12 months, and 12 patients (23 %) were aged 12-24 months . The annual incidence per 100,000 children aged between 1 and 2 years was 17.75 cases (95 % CI: 11.59 26.01) and 8.39 cases (95 % CI: 4.67 15.79) respectively, and that for children in the first 2 and 5 years of life was 13.13 (95 % CI: 9.29 18.02) and 6.29 (95 % CI: 4.57 8.,45) cases respectively . Nearly half the strains isolated (47.6 %) showed reduced sensitivity to penicillin . The most frequent serotype was 19F (12 cases {28.6 %}) . Eighty percent of the isolated serotypes were included in the formula of the heptavalent conjugate vaccine . CONCLUSIONS: The incidence of pneumococcal meningitis in children from five Spanish Autonomous Communities is high, nearly twice that found in a prior retrospective studied performed in the same population 1-3 years previously . Almost all the isolated serotypes were included in the heptavalent conjugate vaccine . Half the strains showed reduced sensitivity to penicillin.

J Immunol, 2002 Nov 1, 169(9), 5300 - 7
Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness; Rha YH et al.; Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses . We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guerin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR) . Mice were sensitized to OVA by i.p . injection and then challenged by OVA inhalation . Hsp were administered to each group by i.p . injection before sensitization and challenge . Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals . Administration of M . leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner . Treatment with M . leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-gamma production were increased . Furthermore, M . leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction . In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production . Depletion of gamma/delta T lymphocytes before sensitization and challenge abolished the effect of M . leprae hsp treatment on AHR . These results indicate selective and distinctive properties among the hsp, and that M . leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.

Arch Dis Child Fetal Neonatal Ed, 2002 Nov, 87(3), F224 - 5
A case of neonatal stridor; Abdullah V et al.; A case is reported of a retropharyngeal abscess in a neonate who presented with increasing stridor since birth . Group B streptococcus was cultured from the abscess contents and the maternal birth tract.

Clin Exp Immunol, 2002 Nov, 130(2), 319 - 24
Heterogeneity of humoral immune abnormalities in children with Nijmegen breakage syndrome: an 8-year follow-up study in a single centre; Gregorek H et al.; During an 8-year period of observation, defects of immune responses were characterized and monitored in 40 of 50 Polish children with Nijmegen breakage syndrome referred to the Children's Memorial Health Institute in Warsaw . The following parameters were determined at diagnosis: (1) concentrations of serum IgM, IgG, IgA; (2) concentrations of IgG subclasses; and (3) lymphocyte subpopulations . In addition, naturally acquired specific antibodies against Streptococcus pneumoniae were determined in 20 patients with a history of recurrent respiratory infections . During follow-up, total serum immunoglobulins and IgG subclasses were monitored systematically in 17 patients who did not receive immunomodulatory therapy . Moreover, anti-HBs antibody response was measured after vaccination of 20 children against HBV . We found that the immune deficiency in NBS is profound, highly variable, with a tendency to progress over time . Systematic monitoring of the humoral response, despite good clinical condition, is essential for early medical intervention.

Clin Microbiol Infect, 2002 Oct, 8(10), 680 - 3
Comparative in vitro activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, pristinamycin, quinupristin-dalfopristin and linezolid against ofloxacin-intermediate and -resistant Streptococcus pneumoniae; Fredenucci I et al.; Screening by ofloxacin disk was carried out on 1158 strains of Streptococcus pneumoniae in order to investigate the in vitro bacteriostatic activity of penicillin G, levofloxacin, moxifloxacin, telithromycin, linezolid, pristinamycin and quinupristin-dalfopristin against ofloxacin-intermediate and -resistant S . pneumoniae strains . It was concluded that these new antimicrobial agents could be useful for the treatment of pneumococcal infections caused by penicillin-sensitive and -resistant S . pneumoniae, and would represent a valid therapeutic option for patients allergic to beta-lactams, should they prove to be potent in vivo.

Clin Microbiol Infect, 2002 Oct, 8(10), 613 - 22
Antibiotic tolerance in pneumococci; Henriques Normark B et al.; When bacteria such as Staphylococcus aureus and Streptococcus pneumoniae are exposed to lytic antibiotics such as penicillin and vancomycin, a self-induced killing process is initiated in the organism . This killing occurs via both non-lytic and lytic processes . Recent data suggest that the non-lytic killing system, which might affect the cytoplasmic membrane, secondarily activates murein hydrolases that eventually lyse the cell . Disturbances in this suicide pathway can lead to antibiotic tolerance, a process whereby the antibiotic still exerts its bacteriostatic effects but the self-induced killing system is impaired . In mutants obtained in vitro, signaling pathways have been affected that show either increased or decreased antibiotic-induced killing . Among clinical isolates of S . pneumoniae that are tolerant to penicillin and/or vancomycin, we do not yet know whether these signaling pathways are affected . We could, however, demonstrate that the activity of murein hydrolases is negatively controlled by the production of capsular polysaccharides in one vancomycin-tolerant isolate . Hence, type and level of capsular expression might constitute one factor that determines the degree of lysis, once the killing signal has been elicited by the antibiotic.

Salud Publica Mex, 2002 Sep-Oct, 44(5), 437 - 41
{Antimicrobial sensitivity and characterization of Streptococcus pyogenes strains isoleated from a scarlatina outbreak}; Gonzalez Pedraza-Aviles A et al.; OBJECTIVE: To evaluate the in vitro activities of 13 antimicrobial agents against 47 group A Streptococcus pyogenes (GAS) strains, and to determine the presence of genes encoding streptococcal pyrogenic exotoxin A (SpeA) and the M-protein serotypes . MATERIALS AND METHODS: A cross-sectional study was conducted at Centro de Salud Dr . Jose Castro Villagrana, during a scarlet fever outbreak occurring between December 1999 and January 2000, among 137 children at Colegio Espiritu de America . Minimum Inhibitory Concentrations (MICs) were obtained by the semiautomated microdilution method . Automated DNA sequencing was used for analysis of sequence variation in genes encoding the M protein, and SpeA . RESULTS: All strains were sensitive to betalactams and clindamycin . Six (12.7%) were resistant to erythromycin . The M2 type was the most frequently isolated GAS (27); almost all (96%) bacteria with the SpeA gene had the gene encoding the M2 protein . CONCLUSIONS: The recent resurgence of GAS infections calls for molecular epidemiology research and studies on the sensitivity to macrolides and beta-lactams.

Best Pract Res Clin Rheumatol, 2002 Jul, 16(3), 481 - 94
Rheumatic fever and post-streptococcal arthritis; Hilario MO et al.; Rheumatic fever resulting from group A beta-haemolytic Streptococcus infection continues to be a prevalent disease and an important cause of morbidity and mortality in developing countries . Molecular mimicry and CD4 T lymphocytes, interleukins and adhesion molecules play a crucial role in the pathogenesis of this disease . Arthritis, followed by carditis and chorea, are the main manifestations of the disease . Evidence of asymptomatic carditis has been increasing; however, abnormality identified by echo-Doppler evaluation is not considered as a criterion for diagnosis of rheumatic carditis . Benzathine penicillin is still the best therapeutic option for the treatment of streptococcal infection and secondary prophylaxis, due to its efficacy and low cost.

J Infect, 2002 Oct, 45(3), 197 - 8
Spontaneous bacterial peritonitis from Streptococcus salivarius in a compromised host; Peterson MC; A seriously ill patient with cirrhosis and resistant ascites from hepatitis C and alcohol abuse abruptly deteriorated . He developed encephalopathic changes, abdominal pain and tenderness and was suspected of having spontaneous bacterial peritonitis . The peritoneal fluid contained many granulocytes and Steptococcus salivarius was isolated from the fluid.

J Infect, 2002 Oct, 45(3), 139 - 43
Epidemiology of invasive streptococcus pneumoniae infections in children in Spain, 1996-1998; Diez-Domingo J et al.; BACKGROUND: Streptococcus pneumoniae is a significant cause of meningitis and septicemia in early infancy, being associated to a high case-fatality rates and serious sequelae . OBJECTIVE: To investigate the burden of invasive disease caused by S . pneumoniae in Valencia, Spain, during a three-year period (1996-1998) . METHODS: Hospital-based prospective active surveillance program for invasive bacterial diseases in children < or = 15 years of age in Valencia, from December 1, 1995 to January 1999 . RESULTS: A total of 94 cases of invasive pneumococcal disease were detected in patients < or = 15 years of age . The overall annual incidence of invasive pneumococcal disease was 4.6/100,000 persons, < or = 15 years of age . The incidence of invasive disease and meningitis was higher among children younger than 2 years of age (16.8 and 3.8, respectively) . Serotypes 19, 14 and 6 accounted for 83% of the isolates . CONCLUSIONS: The age distribution of invasive pneumococcal disease and meningitis shows a peak in the first two years of life and a decline thereafter . Serotypes 19, 14 and 6 are those primarily responsible for invasive pneumococcal disease in children of this region of Spain.

Microb Pathog, 2002 Oct, 33(4), 185 - 92
Response regulator important in pathogenesis of Streptococcus suis serotype 2; de Greeff A et al.; In this study, we describe the first response regulator of Streptococcus suis serotype 2, designated RevS . RevS was cloned and the sequence was determined . No histidine kinase was found in the vicinity ofrevS, therefore RevS was considered to be an orphan response regulator . An isogenic knock-out mutant of RevS was shown to be attenuated in colonising the S . suis specific organs in a competitive assay in four piglets, indicating thatrevS plays a role in the pathogenesis of S . suis infections . We analysed the protein expression profiles of various fractions of the wild-type strain 10 and the mutant strain 10DeltaRevS . The expression of known virulence factors ofS . suis by wild-type and the mutant strain, was not different . However, one protein in the protoplast fraction, with unknown identity was shown to be repressed by revS in the exponential growth phase of the mutant.

Int J Antimicrob Agents, 2002 Oct, 20(4), 235 - 47
Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate; File TM Jr et al.; The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of </=4 mg/l, was evaluated in patients with respiratory infections caused by S . pneumoniae, including PRSP (penicillin MICs 2-16 mg/l) . Data from nine clinical studies were combined (total intent-to-treat N=5531) . Six randomized, double-blind studies used levofloxacin 500 mg od in acute bacterial sinusitis (ABS), levofloxacin 500 mg od in acute exacerbations of chronic bronchitis (AECB), clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators . The three remaining studies (two in ABS and one in CAP) were non-comparative . In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S . pneumoniae infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA MICs of >/=4 mg/l . In the pooled comparator group, the success rate at follow-up was 86.5% (45/52) . For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators . AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S . pneumoniae infections . Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S . pneumoniae and in patients at high risk of antimicrobial-resistant S . pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3648 - 9
In vivo penicillin MIC drift to extremely high resistance in Serotype 14 Streptococcus pneumoniae persistently colonizing the nasopharynx of an infant with chronic suppurative lung disease: a case study; Leach AJ et al.; This is the first report of in vivo pneumococcal penicillin MIC drift from 4.0 to 16.0 mg/liter, possibly associated with alterations in the pbp1a gene . The case presented here is of an infant with early onset recurrent pneumonia and chronic bronchitis requiring repeated antibiotics.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3630 - 3
Pharmacokinetics and pharmacodynamics of gatifloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a granulocyte-rich exudate; Trampuz A et al.; The pharmacokinetics of gatifloxacin were assessed in serum and in skin blister fluid (SBF), as was the pharmacodynamic activity in SBF . Five hours after a single dose of gatifloxacin, SBF killed 2.5 logs of Streptococcus pneumoniae and 1.5 log of Staphylococcus aureus during a 2-h incubation ex vivo.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3512 - 7
Emergence in Vietnam of Streptococcus pneumoniae resistant to multiple antimicrobial agents as a result of dissemination of the multiresistant Spain(23F)-1 clone; Parry CM et al.; Surveillance for Streptococcus pneumoniae resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam . The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied . A penicillin-nonsusceptible pneumococcus (MIC, > or =0.1 micro g/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (P < 0.0001) . Pneumococcal isolates resistant to penicillin (MIC, > or =2.0 micro g/ml) increased from 0% (0 of 24) to 28% (10 of 36) (P = 0.002) . Only one isolate was ceftriaxone resistant (MIC, 2.0 micro g/ml) . Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (P = 0.0001) . Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (P = 0.005) and previous antibiotic therapy (P = 0.025) . Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain(23F)-1 clone . The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines . Our findings point to the recent introduction and spread of the Spain(23F)-1 clone of penicillin-resistant pneumococci in Vietnam . Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis . Pneumococcal vaccination may help to control this problem.

Antimicrob Agents Chemother, 2002 Nov, 46(11), 3484 - 9
In vivo pharmacodynamics of a new oxazolidinone (linezolid); Andes D et al.; Linezolid is a new oxazolidinone with activity against gram-positive cocci . We determined the in vivo activity of linezolid against four strains of Staphylococcus aureus (two methicillin-susceptible S . aureus {MSSA} strains and two methicillin-resistant S . aureus strains) and one penicillin-susceptible Streptococcus pneumoniae (PSSP) strain, two penicillin-intermediate S . pneumoniae strains, and five penicillin-resistant S . pneumoniae strains . The mice had 10(6.3) to 10(7.7) CFU/thigh before therapy and were then treated for 24 h with 5 to 1,280 mg of linezolid/kg divided into 1, 2, 4, 8, or 16 doses . The killing activities after 4 h of therapy ranged from 2.4 to 5.0 log(10) CFU/thigh against S . pneumoniae and 1.35 to 2.2 log(10) CFU/thigh against S . aureus . Increasing doses produced minimal concentration-dependent killing; doses of 20 and 80 mg/kg produced no in vivo postantibiotic effects (PAEs) with PSSP and modest PAEs (3.4 and 3.2 h) with MSSA . Pharmacokinetic studies at doses of 20 and 80 mg/kg by high-pressure liquid chromatography analysis exhibited peak dose values of 0.68 and 0.71 and elimination half-lives of 1.02 and 1.00 h . Linezolid MICs ranged from 0.5 to 1.0 micro g/ml for S . pneumoniae and from 1.0 to 4.0 micro g/ml for S . aureus . A sigmoid dose-response model was used to estimate the dose required to achieve a net bacteriostatic effect over 24 h . Static doses against S . pneumoniae ranged from 22.2 to 97.1 mg/kg/24 h and from 133 to 167 mg/kg/24 h for S . aureus . The 24-h area under the concentration-time curve (AUC)/MIC ratio was the major parameter determining the efficacy of linezolid against PSSP (R(2) = 82% for AUC/MIC versus 57% for T>MIC and 59% for the peak level in serum/MIC {peak/MIC}) . It was difficult to determine the most relevant pharmacokinetic/pharmacodynamic parameter with S . aureus, although the outcomes correlated slightly better with the 24-h AUC/MIC ratio (R(2) = 75%) than with the other parameters (T>MIC R(2) = 75% and peak/MIC R(2) = 65%) . The 24-h AUC/MIC ratio required for a bacteriostatic effect with linezolid varied from 22 to 97 (mean = 48) for pneumococci and from 39 to 167 (mean = 83) for staphylococci . Based upon a pharmacokinetic goal of a 24-h AUC/MIC of 50 to 100, a dosage regimen of 600 mg given either intravenously or orally twice daily would achieve success against organisms with MICs as high as 2 to 4 micro g/ml.

Vet Microbiol, 2002 Nov 6, 89(4), 311 - 21
Construction of a stable non-mucoid deletion mutant of the Streptococcus equi Pinnacle vaccine strain; Walker JA et al.; Streptococcus equi causes equine strangles, a purulent lymphadenopathy of the head and neck . An avirulent, non-encapsulated strain (Pinnacle) has been used widely in North America as an intranasal vaccine . The aim of the study was to create a specific mutation of the hyaluronate synthase (hasA) gene in Pinnacle to permanently abolish the production of capsule and provide an easily recognisable genetic marker . An internal fragment of hasA was generated by PCR and cloned into pTW100 (Microscience, UK) . An encapsulated revertant of Pinnacle was then transformed with the recombinant plasmid by electroporation and cultured under conditions to promote homologous recombination . Among 90 spectinomycin resistant transformants observed, one non-mucoid (non-encapsulated) spectinomycin resistant colony was detected . The presence of plasmid sequence within the hasA gene was confirmed by the PCR . After six passages in antibiotic-free medium, four non-mucoid spectinomycin sensitive colonies were found . Sequence analysis of one of these clones, designated Pinnacle HasNeg, revealed loss of the 3' end of the hasA and the 5' end of the hasB genes . This deletion mutant should serve as a useful candidate to replace Pinnacle since it cannot revert to a mucoid phenotype and can be distinguished genetically from wild type strains.

Eur J Biochem, 2002 Oct, 269(20), 5066 - 75
Inhibition of hyaluronan synthesis in Streptococcus equi FM100 by 4-methylumbelliferone; Kakizaki I et al.; As observed previously in cultured human skin fibroblasts, a decrease of hyaluronan production was also observed in group C Streptococcus equi FM100 cells treated with 4-methylumbelliferone (MU), although there was no effect on their growth . In this study, the inhibition mechanism of hyaluronan synthesis by MU was examined using Streptococcus equi FM100, as a model . When MU was added to a reaction mixture containing the two sugar nucleotide donors and a membrane-rich fraction as an enzyme source in a cell-free hyaluronan synthesis experiment, there was no change in the production of hyaluronan . On the contrary, when MU was added to the culture medium of FM100 cells, hyaluronan production in the isolated membranes was decreased in a dose-dependent manner . However, when the effect of MU on the expression level of hyaluronan synthase was examined, MU did not decrease either the mRNA level of the has operon containing the hyaluronan synthase gene or the protein level of hyaluronan synthase . Solubilization of the enzyme from membranes of MU-treated cells and addition of the exogenous phospholipid, cardiolipin, rescued hyaluronan synthase activity . In the mass spectrometric analysis of the membrane phospholipids from FM100 cells treated with MU, changes were observed in the distribution of only cardiolipin species but not of the other major phospholipid, PtdGro . These results suggest that MU treatment may cause a decrease in hyaluronan synthase activity by altering the lipid environment of membranes, especially the distribution of different cardiolipin species, surrounding hyaluronan synthase.

Infect Immun, 2002 Nov, 70(11), 6504 - 8
Decreased virulence of a pneumolysin-deficient strain of Streptococcus pneumoniae in murine meningitis; Wellmer A et al.; Pneumolysin, neuraminidases A and B, and hyaluronidase are virulence factors of Streptococcus pneumoniae that appear to be involved in the pathogenesis of meningitis . In a murine model of meningitis after intracerebral infection using mutants of S . pneumoniae D39, only mice infected with a pneumolysin-deficient strain were healthier at 32 and 36 h, had lower bacterial titers in blood at 36 h, and survived longer than the D39 parent strain . Cerebellar and spleen bacterial titers, meningeal inflammation, and neuronal damage scores remained uninfluenced by the lack of any of the virulence factors.

Infect Immun, 2002 Nov, 70(11), 6485 - 8
Opsonization of Actinobacillus actinomycetemcomitans by immunoglobulin G antibody reactive with phosphorylcholine; Purkall D et al.; We used two strains of Actinobacillus actinomycetemcomitans, one bearing phosphorylcholine (PC) (strain D045D-40) and one devoid of PC antigens (strain DB03A-42), as well as a nonencapsulated strain of Streptococcus pneumoniae (strain 39937), to examine the opsonic properties of physiological concentrations (</=30 micro g/ml) of purified human anti-PC immunoglobulin G (IgG) . Anti-PC bound to both A . actinomycetemcomitans DO45D-40 and S . pneumoniae 39937 and induced superoxide anion production by polymorphonuclear neutrophils; induction of the oxidative burst was inhibited by antibodies to either CD16 or CD32 . Thus, anti-PC IgG at concentrations present in most human sera promotes the opsonization of PC-expressing strains of A . actinomycetemcomitans in the absence of complement, implying that anti-PC may be a protective antibody against such strains of bacteria.

Infect Immun, 2002 Nov, 70(11), 6121 - 8
Genetic analysis and functional characterization of the Streptococcus pneumoniae vic operon; Wagner C et al.; The vic two-component signal transduction system of Streptococcus pneumoniae is essential for growth . The vic operon comprises three genes encoding the following: VicR, a response regulator of the OmpR family; VicK, its cognate histidine kinase; and VicX, a putative protein sharing 55% identity to the predicted product (YycJ) of an open reading frame in the Bacillus subtilis genome . We show that not only is vic essential for viability but it also influences virulence and competence . A putative transcriptional start site for the vic operon was mapped 16 bp upstream of the ATG codon of vicR . Only one transcript of 2.9 kb, encoding all three genes, was detected by Northern blot analysis . VicK, an atypical PAS domain-containing histidine kinase, can be autophosphorylated in vitro, and VicR functions in vitro as a phospho-acceptor protein . (PAS is an acronym formed from the names of the proteins in which the domains were first recognized: the Drosophila period clock protein {PER}, vertebrate aryl hydrocarbon receptor nuclear translocator {ARNT}, and Drosophila single-minded protein {SIM}.) PAS domains are commonly involved in sensing intracellular signals such as redox potential, which suggests that the signal for vic might also originate in the cytoplasm . Growth rate, competence, and virulence were monitored in strains with mutations in the vic operon . Overexpression of the histidine kinase, VicK, resulted in decreased virulence, whereas the transformability of a null mutant decreased by 3 orders of magnitude.

Biochem Biophys Res Commun, 2002 Oct 18, 298(1), 75 - 9
Binding of Streptococcus mutans to extracellular matrix molecules and fibrinogen; Beg AM et al.; We have determined the ability of Streptococcus mutans cells to bind to extracellular matrix (ECM) molecules and fibrinogen . S . mutans cells were found to bind fibronectin, laminin, collagen type I, and fibrinogen . An isogenic S . mutans strain with a defect in the expression of the major surface protein of S . mutans, antigen I/II, possessed a reduced ability to bind fibronectin, collagen, and fibrinogen but not laminin, suggesting that antigen I/II contributes during pathological processes to the interaction of S . mutans cells with fibronectin, collagen type I, and fibrinogen.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 117 - 25
Efficacy and safety of gatifloxacin in elderly outpatients with community-acquired pneumonia; Nicholson SC et al.; To evaluate the safety and efficacy of gatifloxacin in adults <65, 65 to 79, or > or =80 years old with community-acquired pneumonia, adult male and female outpatients from general community-based practices were enrolled in an open-label, multicenter, noncomparative study . Gatifloxacin 400 mg once daily was administered for seven to 14 days . Medical history, physical examination, signs and symptoms of infection, Gram stain and culture if specimen available, clinical response, and safety were determined . Of 1655 treated patients, 1103 were at least 65 years old, 405 were 65 to 79, and 147 were at least 80 . Patients > or =80 years old presented with chills, chest pain, fever, or headache less often than younger patients . Cure rates were 95.5% for patients <65 years old, 96.2% for those 65 to 79, and 90.2% for those at least 80 years old . Neither the frequency nor susceptibility of isolated pathogens appeared to differ with age . Between 93.7% and 100% of subsets of the two younger groups with verified Streptococcus pneumoniae or Hemophilus influenzae were cured . All oldest-group patients in the subset with verified S . pneumoniae and 71.4% (7) of patients with H . influenzae were cured . Each age group, including current or past smokers and patients receiving medications for concomitant conditions, tolerated treatment well . Gatifloxacin is safe and efficacious in adults of any age with community-acquired pneumonia, including the elderly up to 100 years old and patients with S . pneumoniae including penicillin-resistant strains.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 93 - 100
Gatifloxacin used for therapy of outpatient community-acquired pneumonia caused by Streptococcus pneumoniae; Jones RN et al.; Gatifloxacin is an advanced-generation fluoroquinolone with demonstrated efficacy and safety as therapy for community-acquired pneumonia (CAP) . As part of a phase IV postmarketing surveillance program (TeqCES), 136 outpatients with CAP whose sputum was culture-positive for Streptococcus pneumoniae were enrolled in an open-label trial of oral gatifloxacin 400 mg daily for 7 to 14 days . An antibiogram of isolates showed 100% susceptibility to gatifloxacin (MIC(90) 0.5 micro g/mL) and respective susceptibilities of 67%, 70%, and 80% to penicillin, erythromycin, and tetracycline . Clinical cure was achieved in 95.3% of evaluable patients, including seven patients infected with penicillin-resistant S . pneumoniae (MIC > or =2 micro g/mL) . The bacteriologic eradication rate for S . pneumoniae was 94.5% . Diarrhea, nausea, and dizziness, the most common adverse events in CAP patients (<3%), were generally mild to moderate; no serious adverse events were recorded . These results support recommendations to treat CAP, particularly due to S . pneumoniae including multidrug-resistant strains, with the newer 8-methoxy-fluoroquinolone, gatifloxacin.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 77 - 84
Gatifloxacin phase IV surveillance trial (TeqCES study) utilizing 5000 primary care physician practices: report of pathogens isolated and susceptibility patterns in community-acquired respiratory tract infections; Pfaller MA et al.; Recently FDA-approved fluoroquinolones like gatifloxacin possess enhanced activity against Gram-positive pathogens such as Streptococcus pneumoniae . However, experience with adverse events among previously used fluoroquinolones has led to expanded post-marketing investigations of clinical efficacy and safety . An open-label gatifloxacin trial was initiated in early 2000, using 2795 (>15000 enrolled cases) primary care providers for treatment of community-acquired respiratory tract infections (CARTI) such as community-acquired pneumonia (CAP), acute bacterial exacerbation of chronic bronchitis (ABECB), acute sinusitis . Microbiology specimens and sputum slides were referred to a reference laboratory, pathogens identified and reference antimicrobial susceptibility tests performed . Results were classified by infection site, geographic census region and patient profile/demographics . The most frequent pathogens were: for CAP (n = 384)-S . pneumoniae (37%) > Hemophilus influenzae (31%) > Moraxella catarrhalis (13%); for ABECB (528)-H . influenzae (37%) > M . catarrhalis (26%) > S . pneumoniae (17%); and for sinusitis (2691)-M . catarrhalis (29%) > H . influenzae (24%) > S . pneumoniae (17%) . H . parainfluenzae (ABECB) and S . aureus (sinusitis) were also commonly isolated . CAP S . pneumoniae isolates had significantly less high-level resistance (5% at > or =2 micro g/ml) than those isolates from ABECB or sinusitis (13-15%) . United States census zone differences in S . pneumoniae resistance were identified (greatest in West or East South Central, South Atlantic) . S . pneumoniae macrolide resistance was high (23-33%) and H . influenzae clarithromycin susceptibility was only 56-62% . beta-lactamase rates in H . influenzae and M . catarrhalis were 21-29% and 88-92%, respectively . Only one S . pneumoniae was not susceptible to gatifloxacin, and this new fluoroquinolone was fourfold more potent than levofloxacin (MIC(50,) 0.25 vs . 1 micro g/ml) . This Phase IV surveillance trial (TeqCES) confirmed the clinical importance of S . pneumoniae, H . influenzae and M . catarrhalis in CARTI, and high fluoroquinolone potency/spectrum (>97% susceptible) . beta-lactams and macrolides continue to be compromised by increasing resistances in pathogens isolated in these monitored primary care settings.

Diagn Microbiol Infect Dis, 2002 Sep, 44(1), 43 - 9
Pharmacodynamics of 750 mg and 500 mg doses of levofloxacin against ciprofloxacin-resistant strains of Streptococcus pneumoniae; Lister PD; An in vitro pharmacokinetic model (IVPM) was used to evaluate the pharmacodynamics of the 750 mg and 500 mg doses of levofloxacin against 4 ciprofloxacin-nonsusceptible Streptococcus pneumoniae . Levofloxacin MICs ranged from 1.4 to 3.2 micro g/ml . Log-phase cultures (5 x 10(7) cfu/ml) were inoculated into the IVPM and exposed to the peak free-drug concentrations of levofloxacin achieved in human serum with each dose . Levofloxacin was dosed at 0 and 24 h, elimination pharmacokinetics were simulated, and viable counts were measured over 30 h . The 750 mg dose was rapidly bactericidal against all 4 strains, achieving eradication within 30 h . Against strains with levofloxacin MICs of 1.4 and 1.8 micro g/ml, the 500 mg dose exhibited pharmacodynamics similar to the 750 mg dose . In contrast, against strains with levofloxacin MICs of 2.6 and 3.2 micro g/ml, viable counts never fell below 10(4) cfu/ml . The rapid killing and eradication of these pneumococci by the 750 mg dose warrant the clinical evaluation of this new dose in the treatment of pneumococcal infections.

J Matern Fetal Neonatal Med, 2002 Feb, 11(2), 84 - 8
Chlorhexidine vaginal flushings versus systemic ampicillin in the prevention of vertical transmission of neonatal group B streptococcus, at term; Facchinetti F et al.; OBJECTIVE: To investigate the efficacy of intrapartum vaginal flushings with chlorhexidine compared with ampicillin in preventing group B streptococcus transmission to neonates . METHODS: This was a randomized controlled study, including singleton pregnancies delivering vaginally . Rupture of membranes, when present, must not have occurred more than 6 h previously . Women with any gestational complication, with a newborn previously affected by group B streptococcus sepsis or whose cervical dilatation was greater than 5 cm were excluded . A total of 244 group B streptococcus-colonized mothers at term (screened at 36-38 weeks) were randomized to receive either 140 ml chlorhexidine 0.2% by vaginal flushings every 6 h or ampicillin 2 g intravenously every 6 h until delivery . Neonatal swabs were taken at birth, at three different sites (nose, ear and gastric juice) . RESULTS: A total of 108 women were treated with ampicillin and 109 with chlorhexidine . Their ages and gestational weeks at delivery were similar in the two groups . Nulliparous women were equally distributed between the two groups (ampicillin, 87%; chlorhexidine, 89%) . Clinical data such as birth weight (ampicillin, 3,365 +/- 390 g; chlorhexidine, 3,440 +/- 452 g), Apgar scores at 1 min (ampicillin, 8.4 +/- 0.9; chlorhexidine, 8.2 +/- 1.4) and at 5 min (ampicillin, 9.7 +/- 0.6; chlorhexidine, 9.6 +/- 1.1) were similar for the two groups, as was the rate of neonatal group B streptococcus colonization (chlorhexidine, 15.6%; ampicillin, 12%) . Escherichia coli, on the other hand, was significantly more prevalent in the ampicillin (7.4%) than in the chlorhexidine group (1.8%, p < 0.05) . Six neonates were transferred to the neonatal intensive care unit, including two cases of early-onset sepsis (one in each group) . CONCLUSIONS: In this carefully screened target population, intrapartum vaginal flushings with chlorhexidine in colonized mothers display the same efficacy as ampicillin in preventing vertical transmission of group B streptococcus . Moreover, the rate of neonatal E . coli colonization was reduced by chlorhexidine.

Pneumologie, 2002 Oct, 56(10), 605 - 9
{beta-lactam-antibiotics in the treatment of community-acquired respiratory tract infections with penicillin-resistant pneumococci}; Brauers J et al.; Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections . During the last decades in many countries an increase in the spread of antibiotic resistant strains (e . g . against beta-lactams, macrolides, tetracyclin) was observed . Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes . In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L) . Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively . According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft fur Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections . As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains . beta-Lactam-antibiotics highly differ in their in-vitro-activity against S . pneumoniae and their pharmacokinetic properties . In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i . e . not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC) . In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.

J Antibiot (Tokyo), 2002 Aug, 55(8), 722 - 57
New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems; Sunagawa M et al.; Discovery of novel antimicrobial agents effective against infections caused by drug-resistant pathogens is an important objective . In order to find a new parenteral carbapenem antibiotic, which has potent antibacterial activity especially against methicillin-resistant staphylococci, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae, a series of 1beta-methylcarbapenems with thiazol-2-ylthio groups at the C-2 position have been synthesized . Structure-activity relationships were investigated which led to SM-197436 (27), SM-232721 (44) and SM-232724 (41), being selected for further evaluation.

Scand J Infect Dis, 2002, 34(9), 683 - 4
Streptococcus suis infection as a cause of severe illness: 2 cases from Croatia; Kopic J et al.; Streptococcus suis is a zoonotic agent that can be spread to humans, e.g . butchers, abattoir workers and farmers, by contact with pigs . Human infection is most frequently manifested as purulent meningitis, in combination with deafness and ataxia, but there have been rare reports of septic shock leading to multiorgan failure and death . We report 2 patients with S . suis type 1 infection . One patient suffered an abrupt and severe illness, with septic shock leading to multiorgan failure and death, whereas the other presented with purulent meningitis and deafness . Both patients were immunocompromised . They were most likely infected as a result of handling pork at home . In both cases, the infection was due to S . suis type 1, in contrast to previous reports indicating an association between human infection and S . suis type 2 . Epidemiologic surveys of human infection may be of interest, especially among individuals exposed to pigs and pork.

Scand J Infect Dis, 2002, 34(9), 639 - 44
Exploring the pathogenesis of necrotizing fasciitis due to Streptococcus pneumoniae; Kwak EJ et al.; Monobacterial necrotizing fasciitis is a rare form of soft tissue infection usually caused by the group A beta-hemolytic Streptococcus . Soft tissue infection is an uncommon clinical manifestation of invasive disease due to Streptococcus pneumoniae . We describe 3 cases of pneumococcal necrotizing fasciitis and explore potential pathogen-specific mechanisms of pathogenesis . The clinical characteristics of necrotizing fasciitis due to S . pneumoniae and group A beta-hemolytic Streptococcus appear to overlap . The similarities include predominant occurrence in elderly adults with underlying chronic illness, predilection for lower extremity infection, progression to toxic shock-like syndrome and a high case fatality rate . No DNA fragments corresponding to speA, speB or speC were amplified by PCR from the 3 pneumococcal isolates . Western immunoblot revealed no evidence of SpeA, SpeB or SpeC protein expression . Evaluation for protease production and cytotoxicity was unrevealing . The similar clinical presentation of pneumococcal necrotizing fasciitis to the disease caused by the group A beta-hemolytic Streptococcus has important therapeutic implications . The molecular mechanisms underlying the pathogenesis are unclear . Prospective population-based studies are required to define the epidemiology of this infection.

Eur J Clin Microbiol Infect Dis, 2002 Sep, 21(9), 671 - 5 Epub 2002 Sep 10.
Clinical and laboratory characteristics of infective endocarditis when associated with spondylodiscitis; Le Moal G et al.; Spondylodiscitis is rarely observed in association with infective endocarditis (IE) . In the study presented here, 92 cases of definite IE were examined . Spondylodiscitis was present in 14 (15%) cases . The mean age of patients with spondylodiscitis was 69.1+/-13.6 years (range, 33-87 years) . The male-to-female ratio was 8:6 . Predisposing heart disease was found in nine (64.3%) cases . Back pain was reported in all cases . Spondylodiscitis was diagnosed before endocarditis in all cases . The infection affected the lumbar spine in 10 (71%) cases . A bacterium was isolated in all cases: group D Streptococcus ( n=5; 35.7%), coagulase-negative Staphylococcus ( n=4; 28.6%), and others ( n=5) . Endocarditis affected predominantly the aortic valve (43%) . The outcome was favourable in 12 cases . No differences in clinical features, evolution of disease, or laboratory values were found between IE patients with and IE patients without spondylodiscitis . Spondylodiscitis does not appear to worsen prognosis of IE, although the need for cardiac valve replacement seems to be more frequent in IE patients with spondylodiscitis . IE should be included in the differential diagnosis in patients with infectious spondylodiscitis and risk factors for endocarditis . In such patients, echocardiography should be performed routinely.

Eur J Clin Microbiol Infect Dis, 2002 Sep, 21(9), 666 - 70 Epub 2002 Sep 13.
Egg-based media for delayed processing of nasopharyngeal swabs in colonization studies of Streptococcus pneumoniae; Gray BM; This report describes the development and evaluation of a selective egg-based medium for ambient-temperature storage and transport of nasopharyngeal (NP) swabs in colonization studies of Streptococcus pneumoniae . Egg-thioglycolate-antibiotic (ETA) medium is based on Dorset's egg medium but made with thioglycolate broth and the addition of gentamicin (3 mg/l), nalidixic acid (15 mg/l), and amphotericin B (2.5 mg/l) . Laboratory studies were conducted using mock swabs from 34 NP samples with known colony counts of pneumococci, which had previously been frozen in STGG (skim milk, tryptone, glucose, glycerol) broth . ETA facilitated better recovery of pneumococci than did either Stuart's or Amies' transport media . In a field study of 117 children, NP swabs were placed in ETA, after being vortexed in STGG and direct-plated for colony counts . Of 52 swabs that were culture positive for pneumococci, all 52 grew pneumococci after 4 days of storage in ETA, and 49 isolates were recovered after 7 days . Transport media such as Stuart's and Amies' require the processing of swabs within about 24 h, and storage in STGG broth requires freezing at -70 degrees C . ETA should be a useful addition to the storage media available for use in epidemiological studies of pneumococcal colonization, especially in situations where prompt processing, rapid transport, or low-temperature storage are not possible.

Aten Primaria, 2002 Sep 30, 30(5), 269 - 81; discussion 281-3
{Pneumococcal vaccine effectiveness in the elderly . Systematic review and meta-analysis}; Puig-Barbera J et al.; AIM: Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly . DESIGN: Systematic review and meta-analysis . DATA SOURCE . MEDLINE, years 1964 to the 2000; EMBASE, from 1988 to the 2000; Cochrane Library, identified studies and previously published systematic reviews citations peruse, and contacts with field experts . STUDY SELECTION: Clinical trials, cohort and case-control studies, published in Spanish, English or French, that estimated pneumococcal disease rates in vaccinated or not vaccinated elderly . DATA EXTRACTION: The studies were valued independently by four investigators with predefined criteria of validity, such as results comparing rates of disease caused by serotypes included in the vaccine, random allocation, double blind design, included subjects pertaining to the same study base, and losses of less than 10% in clinical trials and 20% in observational studies . RESULTS: Eight clinical trials considered the relative risk (RR) of pneumococcal pneumonia, three did not make estimations on pneumonia originated by serotypes included in the vaccine and only one study fulfilled all the inclusion criteria . Vaccinated versus not vaccinated pneumococcal pneumonia RR was 0.86 (95%CI, 0.24 to 2.99) . Vaccine effectiveness was 14% (95%CI, -199 to 76%) . Ten studies performed estimations on the effectiveness of the vaccine on invasive disease by vaccine serotypes . Of these, two clinical trials and two observational studies fulfilled the required quality criteria . RR of invasive disease was of 0.68 (95%CI, 0.39-1.18); vaccine effectiveness was 32% (95%CI, 18-61%) . CONCLUSIONS: No evidence was found supporting pneumococcal vaccine effectiveness to reduce or avoid S . pneumoniae disease in the elderly.

Gac Sanit, 2002 Sep-Oct, 16(5), 385 - 91
{Invasive pneumococcal disease in children in the region of Murcia (Spain)}; Espin MI et al.; OBJECTIVE: Because of the availability of a conjugate pneumococcal vaccine, the incidence and characteristics of invasive pneumococcal disease in children in the region of Murcia should be determined . This would provide information that could be useful for properly establishing the indications for vaccination . METHODS: A retrospective search was conducted for cases of invasive Streptococcus pneumoniae in children aged less 15 years old treated in hospitals in Murcia from 1991-2000 . The data sources were the databases of the microbiology services, the Minimum Data Set, the Pediatric Admissions Register and the EDO Register . RESULTS: The incidence rate for the period 1996-2000 was 18.25 per 105 children per year for children aged under 1 year in the case of invasive disease (10.6 for meningitis), 13.6 for those under 2 years for invasive disease (6 for meningitis), 8.9 for those under 5 years (1.35 for meningitis) and 3.7 for those under 15 years (1.3 for meningitis) . Twenty-eight percent of the patients presented risk factors . Complications occurred in 35.2% and sequelae occurred in 5% . The mortality rate was 11.8% . The prevalent serogroups were 19, 6, 18, 5, 14 and 23 . CONCLUSIONS: The high percentage of patients with risk factors for invasive pneumococcal disease suggests the need to implement vaccination programs aimed at risk groups . Although the incidence of invasive pneumococcal disease in the region of Murcia differs from that in other areas, the incidence of meningitis is similar to that reported by other studies . Because of the severity of the disease, cost-effectiveness studies to evaluate the possible incorporation of the vaccine in the vaccination calendar are justified.

Neurol Med Chir (Tokyo), 2002 Sep, 42(9), 414 - 6
Fulminant subdural empyema treated with a wide decompressive craniectomy and continuous irrigation--case report; Wada Y et al.; A 56-year-old male presented with fulminant subdural empyema manifesting as rhinorrhea, periorbital cellulitis, fever, convulsions, and consciousness disturbance . Neuroimaging showed pansinusitis with skull destruction and extensive subdural empyema . Decompressive craniectomy, irrigation of the empyema, and subdural drainage were performed . Endoscopic sinus surgery was performed to remove the source of infection at the same time . Streptococcus milleri was cultured from the pus . Continuous irrigation of the subdural space with saline containing gentamicin for 7 days resulted in prompt elimination of pus and debris . The patient was discharged with only a slight neurological deficit.

Infect Dis Clin North Am, 2002 Sep, 16(3), 697 - 712
Skin and soft tissue infections in injection drug users; Ebright JR et al.; Skin and soft tissue infections are the most common cause for hospital admission of injection drug users . Cutaneous and subcutaneous abscesses are the most frequent type of SSTI and occur most commonly when drug users are no longer able to inject intravenously and resort to injection directly into skin or muscle . Abscesses may be difficult to differentiate from uncomplicated cellulitis or may be confused with pseudoaneurysms, hematoma, phlegmon, or thrombosed vein . Special studies, including ultrasonography; CT scans, and MR imaging; or careful incision and inspection may be necessary to clarify the extent of infection and the presence of abscess . These procedures may also help differentiate a subcutaneous abscess from a vascular structure . Uncomplicated cellulitis most commonly responds to antibiotic therapy directed toward Staphylococcus aureus and Streptococcus spp . In several recent studies, cutaneous and subcutaneous abscesses have been found to be caused by polymicrobial infections and to include anaerobic organisms as well as aerobic gram-positive cocci in a little more than 50% of cases . Complete, often repeated, incision and drainage is a prerequisite for successful outcome in these cases . Complications of SSTI are many and are potentially life threatening . They include direct extension of subcutaneous abscess into vital areas or structures, necrotizing fasciitis and myositis, bacteremia, and sepsis . An outbreak of a highly lethal SSTI that recently occurred in Scotland, Ireland, and England seems to have resulted from infection with Clostridia spp, including C . novyi and C . perfringens . A rare but well-documented SSTI in injection drug users is pyomyositis, an abscess-forming infection of skeletal muscle . More than 20 cases have been reported in temperate climates to date . Although not life-threatening, chronic cutaneous venous ulcers of the lower extremities are common and debilitating, requiring long-term multidisciplinary care for successful healing.

Proc Natl Acad Sci U S A, 2002 Oct 15, 99(21), 13855 - 60 Epub 2002 Oct 07.
Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling; Graham MR et al.; Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli . Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans . A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase) . Inactivation of covRS results in enhanced virulence in mouse models of invasive disease . Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions . CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems . Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection . This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.

J Dairy Res, 2002 Aug, 69(3), 375 - 82
Possible labile inhibition of the growth of Streptococcus uberis in milk from cows free from mastitis; Kliem KE et al.; Milk from dairy cows never known to have had an intramammary infection with Streptococcus uberis can inhibit growth of Str . uberis for up to 7 h . This inhibition is abolished if milk is heated to 80 degrees C . Inhibition appears not to be related to immune defences as it occurs in skimmed milk (cell free), is unrelated to the concentration of immunoglobulin and survives heating to 56 degrees C . The effect is partly overcome by addition of selected amino acids and vitamins . It is suggested that the inhibition is caused by a restriction in the supply of essential nutrients part of which may require the conversion of plasminogen to plasmin.

Med Decis Making, 2002 Sep-Oct, 22(5 Suppl), S45 - 57
Cost-effectiveness of the pneumococcal vaccine in healthy younger adults; Pepper PV et al.; OBJECTIVES: Routine vaccination for Streptococcus pneumoniae has been recommended as a cost-effective measure for elderly and immunocompromised patients, yet no analysis has been performed for healthy younger adults in America . The authors evaluated the cost-effectiveness of the pneumococcal vaccine and determined the net health benefits conferred for the healthy young adult population . METHODS: The authors developed a decision model to compare the health and economic outcomes of vaccinate versus do not vaccinate for S . pneumoniae . RESULTS: Vaccinating patients for S . pneumoniae generates benefits that are dependent on incidence rates and the efficacy of the vaccine . In the 22-year-old patient with a pneumonia incidence of 0.3/1000, the vaccine would need to be > 71 percent effective for the vaccination strategy to cost less than $50,000/QALY gained . At an incidence of 0.4/1000, the threshold efficacy is 53 percent, whereas at 0.5/1000 it is 43 percent . In the 35-year-old patient where the incidence of pneumococcal pneumonia is higher (0.85/1000), the vaccine would be cost-effective with an efficacy as low as 30 percent . CONCLUSIONS: Use of the S . pneumoniae vaccine in young adults would provide modest reductions in pneumonia-associated morbidity and mortality . Vaccination of young adults is moderately expensive unless vaccine efficacy is above 50% to 60% . In 35-year-old adults, use of the vaccine is cost-effective even with moderate efficacy.

J Perinatol, 2002 Oct-Nov, 22(7), 580 - 1
Transverse myelitis: unusual sequelae of neonatal group B streptococcus disease; Schimmel MS et al.; Group B streptococcus (GBS) meningitis is one of the most serious infections in the neonatal period . We wish to report a case of transverse myelitis following early onset form of GBS meningitis . The diagnosis and the clinical approach will be discussed.

J Perinatol, 2002 Oct-Nov, 22(7), 523 - 5
The development of a group B streptococcus prevention policy at a community hospital; Clemens CJ et al.; BACKGROUND AND OBJECTIVES: In 1996, the Centers for Disease Control (CDC) issued guidelines for antepartum antibiotic prophylaxis of group B streptococcal (GBS)-positive women . The objective of this study is to document results of a GBS prophylaxis policy at one nonacademically affiliated, community hospital and discern its effectiveness with regard to compliance as well as in decreasing the incidence of early onset GBS (EOGBS) disease . METHODS: The development of a GBS-prevention policy at the Women's Hospital of Greensboro (WHG) was documented by means of interviews and examination of minutes of meetings . Effectiveness of the policy was assessed by calculating the percentage of all GBS+ or unknown mothers who received antepartum antibiotics during a 1-year period . Additionally, all newborns with any positive GBS culture during the past 13 years at WHG were identified . RESULTS: The policy was formulated and distributed during a 6-month period by strong leadership, community "buy-in," and an educational seminar . A preprinted physician order was written so that all GBS-positive/unknown mothers would receive antepartum antibiotics . Additionally, a clinical pathway was used to track and monitor maternal GBS status . During October 1, 1999 to September 30, 2000, 1124 (23.1%) mothers were found to be GBS positive/unknown . Of those who delivered an infant >37 weeks' gestation and who could be linked to the pharmacy database, 777 (91.1%) received antepartum antibiotics . The incidence of EOGBS disease at WHG before 1996 was 1.93 +/- 0.7/1000 births compared to 0.4 +/- 0.05/1000 after the issuance of the guidelines (p = 0.002, t-test) . CONCLUSIONS: Over 90% of GBS-positive mothers were treated with antibiotics at WHG . Associated with this high adherence rate to the CDC guidelines has been a five-fold decrease in the incidence of EOGBS disease . We attribute these results to the implementation of a preprinted physician order sheet to direct intrapartum antibiotics for women with GBS positive or unknown colonization and the use of a clinical pathway to track GBS colonization status.

J Perinatol, 2002 Oct-Nov, 22(7), 516 - 22
Changes in early-onset group B beta hemolytic streptococcus disease with changing recommendations for prophylaxis; Uy IP et al.; OBJECTIVE: To determine the incidence of early-onset group B beta hemolytic streptococcal (EOGBS) infection and the association between changes in the incidence and intrapartum antibiotic prophylaxis (IAP) . STUDY DESIGN: A retrospective population survey of infants with GBS at < 7 days of age with a nested case-control study of non-GBS infants over the same time period, January 1985 to December 1998 . The incidence of GBS and maternal antibiotic treatment during labor was analyzed as a function of time period: prior to publication of guidelines for prevention of EOGBS (1985-1992), following AAP/ACOG guidelines (1993-1995), and following CDC consensus guidelines (1996-1998) . RESULTS: Fifty-six cases of EOGBS infection occurred among 53,088 live births . The incidence declined from 1.5/1000 before any guidelines to 0.67/1000 after AAP/ACOG guidelines (p = 0.004), and continued to decline after the CDC consensus statement (0.28/1000) (p = 0.38) . IAP remained stable (33% of at risk mothers) until after introduction of the CDC consensus guidelines (59%, p = 0.02) . CONCLUSION: IAP did not fully explain the decline in EOGBS incidence in our center.

Microbiology, 2002 Oct, 148(Pt 10), 3255 - 63
Oxidative stress tolerance is manganese (Mn(2+)) regulated in Streptococcus gordonii; Jakubovics NS et al.; The Sca permease in the oral bacterium Streptococcus gordonii is a member of a family of ATP-binding cassette (ABC)-type transporters for manganese (Mn(2+)) and related cations that are associated with streptococcal virulence in a number of infection models . Since Mn(2+) has a protective function against oxidative damage in a variety of bacteria, we have investigated the role of Sca permease in oxidative stress tolerance in Streptococcus gordonii . A single Mn(2+)-dependent superoxide dismutase (SOD), encoded by sodA, is expressed by S . gordonii and was >10-fold up-regulated under oxidative stress conditions . Inactivation of sodA resulted in increased susceptibility of S . gordonii cells to growth inhibition by dioxygen (O(2)), and to killing by paraquat (a superoxide anion generator) and by hydrogen peroxide (H(2)O(2)) . Expression of thiol peroxidase, encoded by the tpx gene located immediately downstream of the scaCBA operon, was also up-regulated under oxidative conditions . Inactivation of tpx led to increased susceptibility of cells to H(2)O(2), but not to O(2) or paraquat . In low-Mn(2+) medium (0.01 micro M Mn(2+)) sodA and tpx genes were transcriptionally down-regulated, SOD activity was reduced and cells were more sensitive to growth inhibition by O(2) . A Sca permease-deficient (scaC) mutant showed further reduced SOD activity and hypersensitivity to O(2) in medium containing <0.1 micro M Mn(2+) . These results demonstrate that the Sca (Mn(2+)) permease in S . gordonii is essential for protection against oxidative stress.

Microbiology, 2002 Oct, 148(Pt 10), 3245 - 54
Influence of proteins Bsp and FemH on cell shape and peptidoglycan composition in group B streptococcus; Reinscheid DJ et al.; Group B streptococcus (GBS) is surrounded by a capsule . However, little is known about peptidoglycan metabolism in these bacteria . In the present study, a 65 kDa protein was isolated from the culture supernatant of GBS and N-terminally sequenced, permitting isolation of the corresponding gene, termed bsp . The bsp gene was located close to another gene, designated femH, and reverse transcription-PCR revealed a bicistronic transcriptional organization for both genes . The Bsp protein was detected in the culture supernatant from 31 tested clinical isolates of GBS, suggesting a wide distribution of Bsp in these bacteria . Overexpression of bsp resulted in lens-shaped GBS cells, indicating a role for bsp in controlling cell morphology . Insertional disruption of femH resulted in a reduction of the L-alanine content of the peptidoglycan, suggesting that femH is involved in the incorporation of L-alanine residues in the interpeptide chain of the peptidoglycan of GBS.

Mol Microbiol, 2002 Oct, 46(1), 87 - 99
A locus of group A Streptococcus involved in invasive disease and DNA transfer; Hidalgo-Grass C et al.; Group A streptococcus (GAS) causes diseases ranging from benign to severe infections such as necrotizing fasciitis (NF) . The reasons for the differences in severity of streptococcal infections are unexplained . We developed the polymorphic-tag-lengths-transposon-mutagenesis (PTTM) method to identify virulence genes in vivo . We applied PTTM on an emm14 strain isolated from a patient with NF and screened for mutants of decreased virulence, using a mouse model of human soft-tissue infection . A mutant that survived in the skin but was attenuated in its ability to reach the spleen and to cause a lethal infection was identified . The transposon was inserted into a small open reading frame (ORF) in a locus termed sil, streptococcal invasion locus . sil contains at least five genes (silA-E) and is highly homologous to the quorum-sensing competence regulons of Streptococcus pneumoniae . silA and silB encode a putative two-component system whereas silD and silE encode two putative ABC transporters . silC is a small ORF of unknown function preceded by a combox promoter . Insertion and deletion mutants of sil had a diminished lethality in the animal model . Virulence of a deletion mutant of silC was restored when injected together with the avirulent emm14-deletion mutant, but not when these mutants were injected into opposite flanks of a mouse . DNA transfer between these mutants occurred in vivo but could not account for the complementation of virulence . DNA exchange between the emm14-deletion mutant and mutants of sil occurred also in vitro, at a frequency of approximately 10-8 for a single antibiotic marker . Whereas silC and silD mutants exchanged markers with the emm14 mutant, silB mutant did not . Thus, we identified a novel locus, which controls GAS spreading into deeper tissues and could be involved in DNA transfer.

Cell Microbiol, 2002 Oct, 4(10), 691 - 700
Role of macrophages in experimental group B streptococcal arthritis; Puliti M et al.; Septic arthritis is a clinical manifestation of group B Streptococcus (GBS) infection in both neonates and adults . Because macrophages are known to participate in tissue injury, the role of this cell population in GBS-induced arthritis was investigated . Mice were rendered monocytopenic by administration of etoposide, a drug that selectively depletes the monocyte/macrophage population and then injected with GBS (1 x 10(7) colony-forming units per mouse) . Appearance of arthritis, mortality, GBS growth in the organs, and local and systemic cytokine production were examined . Etoposide-treated mice had a significantly less severe arthritis than control animals . Histopathological analysis of the joints confirmed clinical observations . Decreased joint levels of the proinflammatory cytokines interleukin 1 (IL-1) beta and IL-6 accompanied the less severe development of arthritis in monocytopenic mice . In contrast, mortality was increased in the etoposide-treated mice compared with controls . Monocytopenic mice exhibited elevated bacterial load in the blood and kidneys at all time points examined . These results indicate that lack of macrophages leads to less severe joint lesions, but also results in impaired clearance of bacteria, and consequent enhancement of mortality rates.

Int J Pediatr Otorhinolaryngol . 2002 Oct 21;66(1):49.
Suppurative intracranial complications of sinusitis in children; Ong YK et al.; OBJECTIVE: A review of suppurative intracranial complications of sinusitis in children . METHODS: Case series review over a two-year period from 1998 to 1999 in a children's hospital, Singapore . RESULTS: There were seven cases, all male, and age range 9 to 14 . Six had subdural empyemas and one had meningitis . The most common presenting symptoms included fever, headache and vomiting . Sinusitis was suspected as the cause in only one patient initially . The intracranial infections were not apparent from the initial brain CT of two patients and were only confirmed later on repeated imaging . Four patients had lumbar punctures without any adverse effects . All seven children had infections involving the frontal, ethmoid and maxillary sinuses and two also had sphenoid involvements . All were treated with high-dose intravenous antibiotics together with drainage of both the intracranial (n=six) and sinus (n=seven) suppurations . Five needed repeated intracranial drainages . Streptococcus species were isolated in five cases . Three patients developed seizures post-operatively which resolved on follow-up . One patient needed a ventriculo-peritoneal shunt for hydrocephalus . All patients had a good Glasgow Outcome Score . The hospital stay ranged from 30 to 89 days with a median of 43 days . CONCLUSIONS: Only males were identified in this review, collaborating the feeling that teenage males are at greatest risk of developing intracranial infections from sinusitis . We recommend that radiologic imaging of the brain for suspected intracranial infection should always include the sinuses as this aids early identification of actual cause . Initial CT imaging may be negative and hence repeated scans are warranted if the index of suspicion is high . The successful outcome of the children in this series supports the opinion that combined aggressive surgical and medical treatment is preferable in this patient population.

Optometry, 2002 May, 73(5), 303 - 10
A 10-year case report and current clinical review of chronic beta-hemolytic streptococcal keratoconjunctivitis; Bachman JA et al.; BACKGROUND: Streptococcus is a common source of bacterial keratoconjunctivitis in adults . Affected patients often report decreased vision, foreign body sensation, redness, and a mucous discharge . Clinical signs reveal diffuse conjunctival injection, a conjunctival papillary response, corneal superficial punctate keratitis, and a mucopurulent discharge with corresponding visual acuity decrease . Culturing is mandatory in hyperacute cases and broad-spectrum treatment is advised until culture results are definitive . Recurrent cases may change in clinical appearance . Bacterial exotoxins may induce a severe inflammatory response as well . CASE REPORT: A case of bilateral recurrent bacterial keratoconjunctivitis in a 61-year-old man is reported, as well as a current clinical review of the literature . Aerobic culture yielded Streptococcus pyogenes, a beta-hemolytic group A streptococcus . After unsuccessful broad-spectrum antibiotic treatment with several agents, culture and sensitivity testing confirmed the diagnosis and adjustment of the treatment plan accordingly was successful . During the following 10 years, there were six episodes in the left eye and three episodes in the right eye with resultant inflammation and comeal pannus . Recent repeat culture and sensitivity testing showed that the streptococcus had changed to an atypical presentation . The university laboratory reported the findings to the State Department of Public Health, as this was a nonrespiratory isolate of group A streptococcus . CONCLUSION: Although culture is indicated in hyperacute bacterial keratoconjunctivitis, consider sensitivity testing in non-responsive cases . If the condition is recurrent and the clinical presentation appears different from previous episodes, suspect that the initial pathogen may be changing . Severe secondary inflammation may occur due to bacterial exotoxin reactions . Identification of the underlying causes is advised.

Microb Drug Resist, 2002 Fall, 8(3), 219 - 26
Genetic relatedness of resistant and multiresistant Streptococcus pneumoniae strains, recovered in the Athens area, to international clones; Tsolia MN et al.; The prevalence of resistance to antibiotics was examined among 318 Streptococcus pneumoniae strains isolated during 1998 and 1999 in a children's hospital in Athens . The rate of resistance to penicillin was 25.8% (intermediate 22%, resistant 3.8%); 42.5% of the strains were resistant to > or = 1 antibiotic and 20% were multidrug resistant . Resistance to penicillin was lowest in invasive strains (8.3%) and highest in ear isolates (31%) . A review of the same microbiology laboratory's records revealed that there has been a gradual increase in penicillin resistance since 1988-1989, when it was 5% . Capsular types were determined for 77 strains resistant to > or = 1 antibiotic, and 69 (90%) of them belonged to the following five serotypes: 19F, 14, 9V, 23F, and 6B . Seventy-five strains were analyzed by pulsed-field gel electrophoresis (PFGE) and 59/75 (79%) shared five electrophoretic types . The largest cluster consisted of 19 serotype 19F strains, of which 18 were nonsusceptible to penicillin and most were multidrug resistant and shared a common and distinct electrophoretic pattern not resembling any known clone . A group of 17 strains that were nonsusceptible to penicillin belonged to serotypes 9V (10), 14 (6), and 19F (1) and shared a common PFGE type similar to the international clone Spain9V-3 . Seven serotype 23F strains, of which five were multidrug resistant, belonged to the international clone Spain23F-1 . Among the strains susceptible to penicillin but resistant to non-beta-lactam antibiotics, the largest cluster consisted of 13 isolates resistant to erythromycin that belonged to serotype 14 and shared an electrophoretic pattern characteristic of the clone England14-9 . Finally, three serotype 6B strains were penicillin susceptible and multidrug resistant and had features similar to the Mediterranean 6B clone . The introduction and spread of several antibiotic-resistant international clones accounts at least in part for the increase in pneumococcal resistance observed in recent years in the Athens metropolitan area.

Microb Drug Resist, 2002 Fall, 8(3), 201 - 8
Epidemiology of invasive pneumococcal infection in Taiwan: antibiotic resistance, serogroup distribution, and ribotypes analyses; Siu LK et al.; From July, 1998, to June, 1999, pneumococcal isolates from 288 patients with invasive disease in Taiwan were serogrouped and tested for their susceptibility to various antibiotics . Automated ribotyping was used to study their molecular epidemiology . The mortality rate among those > or = 65 years was higher than those 18 or 19-64 years (p < 0.001) . The total incidence of infection was significantly higher during the cooler season than the warmer season (p = 0.017) . Among strains isolated from children aged < or = 18 years, 76% were not susceptible to penicillin, a rate that was significantly higher (p < 0.001) than that for adults (45%), as was the susceptibility to azithromycin, erythromycin, and trimethoprim-sulfamethoxazole (p < 0.005) . The most prevalent serogroup encountered in the invasive isolates was 23, followed by 6, 14, 19, and 3 . Isolation of Streptococcus pneumoniae in cerebrospinal fluid was at high rate in children under 5 years (p = 0.00012) . Molecular typing revealed a high degree of polymorphism among the isolates . Among serogroup 23 and 19 isolates, a high proportion had the same ribotypes, the Taiwan23F-15 and Taiwan19F-14 isolates, suggesting the circulation of a Taiwanese epidemic strain . In Taiwan, S . pneumoniae isolates should be tested for their resistance profile for children < or = 18 years old, as these are more likely to harbor high-level resistance . Control of pneumococcal infection with the 7-valent-conjugated vaccine should also be considered because it is estimated that it would cover nearly 90% of the serotypes among pediatric invasive disease.

J Dairy Sci, 2002 Sep, 85(9), 2149 - 54
Molecular typing of Streptococcus uberis strains isolated from cases of bovine mastitis; Wieliczko RJ et al.; The discriminatory power of two polymerase chain reaction-based DNA fingerprinting methods, random amplified polymorphic DNA and repetitive extragenic palindrome were compared by subtyping 128 isolates of Streptococcus uberis cultured from cows in six different dairy herds in New Zealand . The typing results demonstrated that the majority of isolates possessed unique fingerprint profiles except on occasions where multiple isolates were obtained from individual cows . On these occasions, individual quarters of the mammary gland were generally, but not exclusively, infected by the same strain of bacteria . Both random amplified polymorphic DNA and repetitive extragenic palindromic typing assays were simple to perform, relatively inexpensive ($11.00 per reaction), and provided reliable and reproducible results . Furthermore, when these assays were used in conjunction with each other, they provided a means of confirmation of the specific DNA fingerprint patterns obtained.

Arch Pediatr Adolesc Med, 2002 Oct, 156(10), 1005 - 8
Use of simple heuristics to target macrolide prescription in children with community-acquired pneumonia; Fischer JE et al.; BACKGROUND: Macrolides are the first-line antibiotic treatment of community-acquired pneumonia (CAP) . Owing to alarming resistance rates among invasive Streptococcus pneumoniae isolates, particularly in young children, macrolide use should be restricted to patients infected with susceptible pathogens, eg, Mycoplasma pneumoniae . OBJECTIVE: To develop a simple clinical prediction rule for identifying M pneumoniae as the cause of CAP in children . DESIGN AND SETTING: Prospective cohort study in 253 children with radiologically confirmed CAP in a walk-in clinic of a tertiary care hospital . MAIN OUTCOME MEASURES: Mycoplasma infection, proven by results of antibody testing of paired serum samples (gold standard) . We compared the area under the receiver operating characteristic curve (c statistic) of the following 2 prediction models: a scoring system derived from logistic regression analysis and a fast-and-frugal decision tree . RESULTS: Mycoplasma pneumoniae infection was confirmed in 32 (13%) of 253 children . A scoring system based on duration of fever and patient age yielded a c statistic of 0.84 (95% confidence interval {CI}, 0.77-0.91), compared with that of the decision tree (c = 0.76 {95% CI, 0.70-0.83}) . The scoring system identified 75% of all cases as being at high or very high risk for M pneumoniae infection; the decision tree, 72% at high risk . The scoring system would curtail macrolide prescriptions by 75%; the decision tree, by 68% . CONCLUSIONS: In children with CAP, simple clinical decision rules identify patients at risk for M pneumoniae infection . At present US macrolide resistance rates among invasive S pneumoniae isolates, both rules increase the chance of prescribing effective first-line antibiotics compared with general macrolide administration.

Pediatrics, 2002 Oct, 110(4), 690 - 5
Trends in incidence and antimicrobial resistance of early-onset sepsis: population-based surveillance in San Francisco and Atlanta; Hyde TB et al.; OBJECTIVE: Although increased use of intrapartum antibiotics caused significant declines in early-onset group B Streptococcus (GBS) infection, the effect on infections caused by other pathogens is not clear . The objective of this study was to determine trends in the incidence of early-onset sepsis caused by organisms other than group B streptococcus in the era of antimicrobial prophylaxis . METHODS: We conducted surveillance for early-onset sepsis as part of the Active Bacterial Core surveillance . A case was defined as isolation of bacteria from blood or cerebrospinal fluid from an infant who was 0 to 6 days of age and born in the surveillance area during 1998 through 2000 (248 184 births) . RESULTS: We identified 408 cases of early-onset infection . GBS caused 166 (40.7%) cases (52 in 1998, 51 in 1999, and 63 in 2000 for incidences 0.62, 0.62, and 0.76 cases per 1000 live births, respectively) . Other bacterial pathogens were identified in 242 cases (82 in 1998, 79 in 1999, and 81 in 2000 for incidences 0.99, 0.95, and 0.98 per 1000 live births, respectively) of early-onset sepsis . Escherichia coli caused 70 cases (0.25, 0.28, and 0.31 cases per 1000 live births, respectively, in 1998-2000) . The proportion of E coli infections that were resistant to ampicillin increased significantly among preterm infants from 29% (2 of 7) in 1998 to 84% (16 of 18) in 2000 but not in full-term infants: 50% (4 of 8) in 1998 and 25% (1 of 4) in 2000 . CONCLUSIONS: Whereas rates of early-onset sepsis caused by GBS and other pathogens were low and did not change significantly during the study period, antibiotic-resistant E coli infections among preterm infants increased . Overall, these trends are reassuring, but careful evaluation of the increase in resistant infections in very young infants is critical in the future.

Ophthalmology, 2002 Oct, 109(10), 1879 - 86
Group B Streptococcus endogenous endophthalmitis : case reports and review of the literature; Lee SY et al.; PURPOSE: To report five cases of group B Streptococcus endogenous endophthalmitis (GBSEE) and to review the literature . DESIGN: Retrospective, noncomparative, interventional case series and literature review . PATIENTS: All patients with this condition treated at the Singapore National Eye Centre from 1994 through 2001 . INTERVENTIONS: Core or complete vitrectomy and intravitreal and systemic antibiotics . METHODS: A review of the systemic and ocular characteristics and treatment . MAIN OUTCOME MEASURE: Visual outcome . RESULTS: Group B Streptococcus endogenous endophthalmitis developed in four patients after the onset of septic arthritis and in one patient with cervical epidural abscess after acupuncture, presenting as a diffuse endophthalmitis . Group B Streptococcus was isolated in the blood, vitreous, and joints . Despite the use of high-dose intravenous antibiotics within 72 hours of ocular presentation, intravitreal antibiotic injection, and vitrectomy (two eyes), all eyes lost light perception and became phthisical . A survey of the literature revealed that GBSEE is rare and that 17 cases have been reported since 1985 . For purposes of analysis, four of these cases were excluded because of inadequate details and our five cases were included . Group B Streptococcus endogenous endophthalmitis was found to arise from hematogenous spread from cutaneous sites of infection (16.7%), pharyngitis (11.1%), and pneumonia (11.1%) . Septic arthritis (38.9%) and endocarditis (33.3%) were concomitant sites of infection along with endophthalmitis . The septic arthritis typically involved multiple joints . Four patients (22.2%) had diabetes mellitus and three had other underlying predisposing illness . Although most patients received intravenous (83.3%) and intravitreal (55.6%) antibiotics and four eyes underwent therapeutic vitrectomy, useful vision was preserved in only four eyes . Two patients died of sepsis . CONCLUSIONS: Group B Streptococcus endogenous endophthalmitis is a devastating condition often associated with septic arthritis . The visual prognosis is poor, despite therapy.

Vet J, 2002 Sep, 164(2), 116 - 28
Bovine mastitis: an evolving disease; Bradley A; Mastitis remains a major challenge to the worldwide dairy industry despite the widespread implementation of mastitis control strategies . The last forty years have seen a dramatic decrease in clinical mastitis incidence but this has been accompanied by a change in the relative and absolute importance of different pathogens . Escherichia coli and Streptococcus uberis are now the two most common causes of bovine mastitis and are an increasing problem in low somatic cell count herds . This paper reviews the changes in incidence and pattern of mastitis in the UK over the last four decades and discusses some of the possible explanations for these changes . It focuses in particular on apparent changes in the behaviour of E . coli and its ability to cause persistent intramammary infection; which may be as a result of bacterial adaptation or the unmasking of previously unrecognized patterns of pathogenesis . The prospects for novel approaches to mastitis control are discussed, as are the current and future challenges facing the industry.

Lett Appl Microbiol, 2002, 35(4), 301 - 4
Are ruminal bacteria protected against environmental stress by plant antioxidants?
Holovska K, Lenartova V, Holovska K, Pristas P, Javorsky P.
AIMS: To investigate the activity response of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) of the rumen bacterium Streptococcus bovis following exposure to mercury(II) chloride (HgCl(2) in the presence of plant antioxidants . METHODS AND RESULTS: Streptococcus bovis was grown with 0 or 5 microg ml(-1) of HgCl(2) alone or together with antioxidant substances (AOS): seleno-l-methionine (Se), alpha-tocopherol (alpha toc), beta-carotene (beta car), melatonin (mel) . The activities of SOD and GHPx were estimated in supernatants of disrupted bacterial cells . A significant decrease in the Strep . bovis SOD activity in the presence of HgCl(2) and tested AOS, except mel, was observed . The GSHPx activity of Strep . bovis was under the same cultivation conditions nonsignificantly changed and a significant decrease in the GSHPx activity was recorded only in the presence of beta car . CONCLUSIONS: The positive effect of Se, alpha toc and beta car on the elimination of environmental stress, evoked by mercury, in ruminal bacterium Strep . bovis in vitro was documented . SIGNIFICANCE AND IMPACT OF THE STUDY: The potential role of plant antioxidants in elimination of the environmental stress of ruminal bacteria evoked by heavy metals is discussed.

Am J Perinatol, 2002 Aug, 19(6), 341 - 8
Impact of different prevention strategies on neonatal group B streptococcal disease; Vergani P et al.; The objective of this paper is to evaluate the effect of different prevention strategies on the rate of early-onset neonatal group B streptococcus (GBS) disease and mortality . We compared the neonatal mortality and morbidity rates associated with early-onset GBS disease in three periods characterized by different prevention strategies, including no screening for GBS during pregnancy and no standardized chemoprophylaxis (1/1987 to 12/1990), antibiotic prophylaxis only with risk factors for GBS (1/1991 to 12/1994), and universal screening for GBS with rectovaginal cultures and chemoprophylaxis for women with positive results or risk factors (1/1995 to 12/1999) . Statistical analysis included Fisher's exact test and Chi-square, with a two-tailed p <0.05 considered significant . The yearly prevalence of positive GBS cultures was similar throughout the screening period (mean 18%, range 16 to 19%) . Compared with the no prophylaxis group (rate = 4/8,573), introduction of universal screening (rate = 0/13,754, p = 0.02) but not of prophylaxis for risk factors alone (rate = 1/10,303, p = 0.18) significantly decreased the occurrence of GBS-specific neonatal mortality . Universal screening decreased, though not significantly, the GBS-specific neonatal morbidity rates compared with a policy based on risk factors alone (0.4/1000 vs . 0.8/1000, p = 0.29) . Our study had a power to detect a 0.7/1000 difference in the rate of specific morbidity between the two chemoprophylaxis policies (alpha = 0.05, beta= 0.80) . Intrapartum prophylaxis for GBS, using universal screening or risk factors, is associated with a significant reduction in the specific neonatal mortality rate compared with no prophylaxis . Universal screening for GBS leads to a decrease in specific GBS morbidity compared with screening using risk factors alone.

J Antimicrob Chemother, 2002 Oct, 50(4), 597 - 9
Prevalence of erm(A) and mef(B) erythromycin resistance determinants in isolates of Streptococcus pneumoniae from New Zealand; Bean DC et al.; One hundred and twenty-four erythromycin-resistant pneumococcal isolates were examined for the presence of macrolide resistance genes . The erm(B) gene was detected in 118 (95.2%) isolates and the mef(A) gene in 83 (66.9%) isolates . Both the mef(A) and erm(B) genes were detected in 77 (62.1%) isolates . DNA macrorestriction analysis of these isolates identified them as belonging to a single multi-resistant clone.

J Antimicrob Chemother, 2002 Oct, 50(4), 517 - 23
Clinical significance of inhibition kinetics for Streptococcus pyogenes in response to penicillin; Steininger C et al.; OBJECTIVES: The antibiotic mode of action against clinical isolates of Streptococcus pyogenes and physiological factors involved in modifying the inhibitory response to the antibiotic were investigated . METHODS: We developed high-resolution respirometry for continuous monitoring of bacterial growth and inhibition kinetics . One hundred and ten clinical isolates from 90 paediatric patients were tested, including 48 isolates obtained from 28 patients with eradication failure . Respirometric inhibition curves were monitored at 4 mg/L penicillin G over a short 30 min period, corresponding to the drug's serum half-life . RESULTS: None of the clinical isolates exhibited penicillin tolerance . Latency in the respirometric response of S . pyogenes to penicillin increased significantly with decreasing strain-specific respirometric growth rate . No difference in inhibition kinetics was found in vitro for isolates from patients with or without bacteriological treatment failure . CONCLUSIONS: In streptococcal pharyngotonsillitis, tolerance is not a relevant concept to explain bacteriological treatment failure . Definitions of tolerance should be reconsidered in the framework of growth-dependent antibiotic susceptibility.

J Antimicrob Chemother, 2002 Oct, 50(4), 457 - 60
Differences in the susceptibility of Streptococcus pyogenes to rokitamycin and erythromycin A revealed by morphostructural atomic force microscopy; Braga PC et al.; The aim of this study was to use atomic force microscopy (AFM), an innovative type of microscopy, to investigate the different behaviours of erythromycin A (a 14-membered ring) and rokitamycin (a 16-membered ring) in disrupting the morphology of Streptococcus pyogenes with the M phenotype . AFM scanning and sensing of the topography of a sample makes it possible to obtain simultaneous high-resolution digital measurements of the x, y and z coordinates at any point on the bacteria surface . The images obtained before and 2, 4 and 6 h after incubation with erythromycin A (32 mg/L) and rokitamycin (2 mg/L) clearly show that not even high concentrations of erythromycin A interfere with the M phenotype of S . pyogenes, whereas rokitamycin has a progressive action that leads to the formation of abnormally large cells, the loosening of chain structure and the formation of clusters.

Med Clin (Barc), 2002 Sep 21, 119(9), 321 - 6
{Diagnostic methods and treatment of community-acquired pneumonia in Spain: NACE study}; Celis MR et al.; BACKGROUND: Community-acquired pneumonia (CAP) is one of the most frequent infectious disease conditions . With the aim of knowing the diagnostic and therapeutic strategies of CAP in Spanish hospitals we performed a prospective, observational and multicenter study . PATIENTS AND METHOD: Observational study of 468 patients with CAP consecutively evaluated in 21 Spanish hospitals . Clinical, diagnostic, therapeutic and evolutive variables were recorded . RESULTS: We included 468 patients with a mean age of 63 (18) years; 75% of them had some comorbidity . 380 (81%) patients required hospitalization in a conventional ward while 19 (4%) were admitted in an Intensive Care Unit (ICU) . 69 patients (15%) required ICU admission . During the first 24 h of admission, biochemical determinations were performed in 98% of cases, blood gas measurements in 88%, blood cultures in 265 (58%), sputum cultures in 149 (41%) and an invasive diagnostic technique was carried out in 17 cases . In 62 cases (14%), a microbiological diagnosis was achieved . Streptococcus pneumoniae (28 cases) was the most frequent isolate followed by Legionella pneumophila (6 cases) . Clarithromycin was the most frequent antibiotic prescribed (38%), either as monotherapy (28) or in combination (148), followed by amoxicillin-clavulanate (124 cases) . Nine percent of patients were considered non-responders to initial empirical antibiotic tretament . Overall mortality was 6% (25%) and it was significanty higher in non-responders . CONCLUSIONS: In most patients with CAP admitted in Spanish hospitals, a systematic diagnostic approach is lacking . There is an important variability in the administration of antimicrobials, the association of a betalactam plus clarithromycin being the most frequent strategy . Overall mortality is low and significantly higher in those patients with a lack of response to initial antibiotic treatment.

J Infect Dis, 2002 Oct 15, 186(8), 1145 - 54 Epub 2002 Sep 25.
Monocytes maintain tissue factor activity after cytolysis of bacteria-infected endothelial cells in an in vitro model of bacterial endocarditis; Veltrop MH et al.; Intravascular infection with Staphylococcus aureus, Staphylococcus epidermidis, or Streptococcus sanguis can initiate fibrin formation on endocardial tissue, causing bacterial endocarditis . The ability of these bacteria to injure intact endothelial cells (ECs) and to aggravate tissue factor (TF)-dependent coagulation in the presence of blood leukocytes was investigated . Cytolysis of ECs occurred after infection with S . aureus and, with membrane-bound monocytes or granulocytes present, also after infection with S . sanguis or S . epidermidis . Monocytes that subsequently bound to the resultant bacteria-infected subcellular EC matrix (ECM) elicited TF mRNA, TF antigen, and TF activity (TFA) . This was most pronounced in ECM prepared after the cytolysis of ECs by infection with S . aureus or S . epidermidis . We demonstrate that monocytes continue and intensify fibrin formation after lysis of bacteria-infected ECs, which suggests that, during the course of intravascular infection, early fibrin formation shifts from being mediated by EC-derived TFA to being mediated by TFA of monocytes bound to bacteria-infected ECM.

J Infect Dis, 2002 Oct 15, 186(8), 1106 - 14 Epub 2002 Sep 16.
Pneumococcal carriage and otitis media induce salivary antibodies to pneumococcal capsular polysaccharides in children; Simell B et al.; Mucosal immunity likely plays an important role in the defense against Streptococcus pneumoniae . This study examined whether pneumococcal carriage and acute otitis media induce mucosal antibodies to pneumococcal capsular polysaccharides (Pnc-PSs) of types 1, 6B, 11A, 14, 19F, and 23F . Immunoglobulin (Ig) A, IgG, and secretory (S) Ig anti-Pnc-PS antibodies were measured by enzyme immunoassay in the saliva of children at ages 6, 12, 18, and 24 months and were analyzed in relation to the previous pneumococcal findings . A larger proportion of IgA-positive samples and higher concentrations of type-specific IgA antibodies were detected in samples of children with pneumococci of the given types cultured before sampling from nasopharyngeal samples or middle-ear fluid, compared with children who had cultures negative for pneumococci of the indicated types or of all types . The IgA and S-Ig concentrations correlated strongly, which suggests that the anti-Pnc-PS IgA was secretory . Salivary anti-Pnc-PS IgG was detected only rarely.

J Clin Microbiol, 2002 Oct, 40(10), 3848 - 50
Reevaluation of Streptococcus bovis endocarditis cases from 1975 to 1985 by 16S ribosomal DNA sequence analysis; Herrero IA et al.; Studies that detected an association between Streptococcus bovis endocarditis and colon carcinoma have not taken into account the recently identified genetic diversity among organisms historically classified as S . bovis . With near full-length 16S ribosomal DNA sequence analysis, organisms cultured from the blood of endocarditis patients at the Mayo Clinic from 1975 to 1985 and previously identified as S . bovis or streptococcus group D nonenterococci were shown to represent S . bovis biotypes I (11 isolates) and II/2 (1 isolate), S . salivarius (1 isolate), and S . macedonicus (1 isolate) . Two of the S . bovis biotype I cases were associated with colon cancer . Whether S . bovis biotype II or other organisms closely related to and historically identified as S . bovis (e.g., S . macedonicus) are associated with malignant (or premalignant) colon lesions in humans remains to be definitively determined.

J Clin Microbiol, 2002 Oct, 40(10), 3671 - 80
Development of a multilocus sequence typing scheme for the pig pathogen Streptococcus suis: identification of virulent clones and potential capsular serotype exchange; King SJ et al.; Streptococcus suis is an important pathogen of pigs and occasionally causes serious human disease . However, little is known about the S . suis population structure, the clonal relationships between strains, the potential of particular clones to cause disease, and the relevance of serotype as a marker for epidemiology . Here we describe a multilocus sequence typing (MLST) scheme for S . suis developed in order to begin to address these issues . Seven housekeeping gene fragments from each of 294 S . suis isolates obtained from various S . suis diseases and from asymptomatic carriage representing 28 serotypes and nine distinct countries of origin were sequenced . Between 32 and 46 alleles per locus were identified, giving the ability to distinguish >1.6 x 10(11) sequence types (STs) . However only 92 STs were identified in this study . Of the 92 STs 18 contained multiple isolates, the most common of which, ST1, was identified on 141 occasions from six countries . Assignment of the STs to lineages resulted in 37 being identified as unique and unrelated STs while the remaining 55 were assigned to 10 complexes . ST complexes ST1, ST27, and ST87 dominate the population; while the ST1 complex was strongly associated with isolates from septicemia, meningitis, and arthritis, the ST87 and ST27 complexes were found to contain significantly higher numbers of lung isolates . In agreement with the observed distribution of disease-causing isolates of S . suis, most isolates previously characterized as of high virulence in porcine infection models belong to ST1, while isolates belonging to other STs appear to be less virulent in general . Finally nine STs were found to contain isolates of multiple serotypes, and many isolates belonging to the same serotypes were found to have very disparate genetic backgrounds . As well as highlighting that the serotype can often be a poor indicator of genetic relatedness between S . suis isolates, these findings suggest that capsular genes may be moving horizontally through the S . suis population.

J Clin Microbiol, 2002 Oct, 40(10), 3660 - 5
Genotypes of invasive pneumococcal isolates recently recovered from Italian patients; Dicuonzo G et al.; We examined 73 recent invasive pneumococcal isolates within selected areas of Italy for genotypic variability . Thirty-three genomic macrorestriction types were found, three of which represented multiple serotypes . Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types . Of the nine macrorestriction types found among the 22 penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates, seven comprised isolates with allelic profiles showing five to seven allelic matches to profiles in the multilocus sequence typing database ; however, three of the seven profiles represented serotypes not previously associated with these clonal clusters . Two PNSP macrorestriction types represented new clones with unique allelic profiles . Allelic profiles obtained from isolates of 3 of the 25 macrorestriction types found among the 51 penicillin-susceptible S . pneumoniae (PSSP) isolates were closely related to previously described profiles . One PSSP isolate was a novel type 24F isolate related to the multiresistant clone France(9V)-3 . This work reports new PNSP strains and new serotype-clone associations.

J Paediatr Child Health, 2002 Oct, 38(5), 445 - 9
Childhood invasive pneumococcal disease in Tasmania, 1994-2000; Christie DJ et al.; OBJECTIVE: To describe the burden of invasive pneumococcal disease in Tasmanian children, including age-specific incidence and antibiotic-resistance pattern . METHODS: A population-based retrospective study was carried out, examining cases of childhood disease associated with isolates of Streptococcus pneumoniae from normally sterile sites, identified via scrutiny of laboratory records at all major Tasmanian laboratories during a 7-year period between January 1994 and December 2000 . Medical records were sub-sequently examined for information describing the clinical syndrome and course of disease . RESULTS: Invasive pneumococcal disease was identified in 76 children during the 7-year period . The incidence per 100 000 children was 28.5 (95% CI 22.0-36.3) in children under 5 years and 54.3 (95% CI 40.2-71.8) in children under 2 years . The incidence of meningitis in children younger than 2 years was 12.2 (95% CI 6.1-21.8) . Penicillin resistance was observed in 2.6% of cases, with no high level resistance . Predisposing conditions were identified in 34% of children with invasive disease . CONCLUSIONS: The incidence of invasive pneumococcal disease was comparable to many urban populations in Australia . The high rate of predisposing conditions supports the recommendations of the Australian Technical Advisory Group on Immunisation for targeted immunization in this group . The paucity of data describing Indigenous status is an argument for improved data collection in this area . The low level of penicillin resistance necessitates ongoing surveillance, and the lack of serotype information requires prospective data collection.

Eur J Biochem, 2002 Oct, 269(19), 4839 - 51
Processing, stability, and kinetic parameters of C5a peptidase from Streptococcus pyogenes; Anderson ET et al.; A recombinant streptococcal C5a peptidase was expressed in Escherichia coli and its catalytic properties and thermal stability were subjected to examination . It was shown that the NH2-terminal region of C5a peptidase (Asn32-Asp79/Lys90) forms the pro-sequence segment . Upon maturation the propeptide is hydrolyzed either via an autocatalytic intramolecular cleavage or by exogenous protease streptopain . At pH 7.4 the enzyme exhibited maximum activity in the narrow range of temperatures between 40 and 43 degrees C . The process of heat denaturation of C5a peptidase investigated by fluorescence and circular dichroism spectroscopy revealed that the protein undergoes biphasic unfolding transition with Tm of 50 and 70 degrees C suggesting melting of different parts of the molecule with different stability . Unfolding of the less stable structures was accompanied by the loss of proteolytic activity . Using synthetic peptides corresponding to the COOH-terminus of human complement C5a we demonstrated that in vitro peptidase catalyzes hydrolysis of two His67-Lys68 and Ala58-Ser59 peptide bonds . The high catalytic efficiency obtained for the SQLRANISHKDMQLGR extended peptide compared to the poor hydrolysis of its derivative Ac-SQLRANISH-pNA that lacks residues at P2'-P7' positions, suggest the importance of C5a peptidase interactions with the P' side of the substrate.

J Formos Med Assoc, 2002 Jul, 101(7), 509 - 13
Streptococcal toxic shock syndrome manifesting as peritonitis in a child; Liang TC et al.; Streptococcal toxic shock syndrome (TSS) with the initial manifestation of peritonitis is rare . We report the case of a 5-year-old girl who presented with peritonitis and shock . Emergency laparotomy was performed but no perforated visceral organ was found . Acute respiratory distress syndrome, impaired renal function, and coagulopathy developed later . Group A beta-hemolytic Streptococcus (GAS) was isolated from the pleural effusion and the diagnosis of streptococcal TSS was made . This association highlights the need for thorough examination and close observation in the management of childhood peritonitis.

J Formos Med Assoc, 2002 Jul, 101(7), 468 - 71
Clinical characteristics and management of acute suppurative thyroiditis in children; Chang P et al.; BACKGROUND: Acute suppurative thyroiditis is an uncommon disease in children . This paper describes the clinical characteristics and management of children with acute suppurative thyroiditis treated during a 15-year period at National Taiwan University Hospital . PATIENTS AND METHODS: From 1985 to 2000, acute suppurative thyroiditis was diagnosed in 11 previously healthy children (6 boys, 5 girls) at the Department of Pediatrics . Their mean age at diagnosis was 6.4 +/- 4.4 years . Leukocyte count, acute-phase reactants, thyroid function, and thyroid autoantibodies were assessed . Samples were taken by thyroid needle aspiration for cytology study and pus culture . Underlying pyriform sinus fistula (PSF) was demonstrated by barium esophagogram . RESULTS: Leukocytosis was noted in six cases (55%) and acute-phase reactants were elevated in eight cases (73%) . Neither thyroid autoantibodies nor thyroid dysfunction was detected in any of the patients . Barium esophagogram detected PSF in eight of 10 patients examined . Five (45%) patients had recurrent suppurative thyroiditis before surgery . Cytology and pus cultures were available for 10 patients . Polymorphonuclear cells were the main findings in the smear from thyroid aspirates . Twenty-two organisms were isolated from six patients (60%) . Streptococcus species (45%) and anaerobic organisms (41%) were the most common pathogens isolated . Mixed infection was detected in five of six children who had a causative microorganism identified . The microorganisms were all sensitive to amoxicillin-clavulanate . CONCLUSION: PSF plays a role in the pathogenesis of acute suppurative thyroiditis in children . Streptococcus species are the most common pathogens in acute suppurative thyroiditis . Our results suggest that amoxicillin-clavulanate is the drug of choice for the treatment of this disease.

Laryngoscope, 2002 Sep, 112(9), 1657 - 62
Cytokine profiles in a rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection; Hebda PA et al.; OBJECTIVE: Cytokine expression was studied in a rat model of otitis media with effusion . METHODS: The left eustachian tube was obstructed (eustachian tube obstruction {ETO}) in 84 rats . Forty-two ears were challenged with, and those rats were treated from day 2 to day 7 with ampicillin . Twelve rats (6 per group) were killed on days 1, 2, 7, 21, 35, 56, and 112; mucosa was harvested and assayed for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) gene expression, and effusion was assayed for IL-1beta, TNF-alpha, IL-6, IL-10, and macrophage inflammatory protein-2 (MIP-2) protein . RESULTS: Most cytokines were detectable in the effusion from infected ears with ETO on days 1 and 2 only . MIP-2 exhibited a biphasic response . Only effusion MIP-2 was consistently detected in uninfected ears with ETO . Three patterns of mucosal cytokine messenger RNA (mRNA) upregulation were observed: isolated early (IL-1beta, IL-8), isolated late (TNF-alpha, IFN-gamma), and biphasic (MCP-1, IL-6, TGF-beta) responses . Early cytokine mRNA upregulations were observed only in the infected ears with ETO, whereas late upregulations were observed in both groups . CONCLUSIONS: Early expression of the assayed cytokines occurred only in ears with active infection . For both groups, a late upregulation of cytokine message but not protein was documented . The profile of cytokine expression during otitis media episodes may be useful in defining etiology, disease stage, and prognosis.

Acta Crystallogr D Biol Crystallogr, 2002 Oct, 58(Pt 10 Pt 2), 1851 - 3 Epub 2002 Sep 28.
Expression, purification and crystallization of Dpr, a ferritin-like protein from the Gram-positive meningitis-associated bacterium Streptococcus suis; Haataja S et al.; Ferritin-like proteins form a novel family of bacterial proteins with diverse functions, such as DNA binding, iron storage and cell activation . A common structural feature of these proteins is their ability to form spherical dodecamers . Dpr is a ferritin-like protein from the Gram-positive bacterium Streptococcus suis . Full-length and truncated Dpr were expressed and purified as 6xHis-tag fusion proteins . Crystals of truncated Dpr suitable for X-ray diffraction analysis were obtained after the removal of the N-terminal affinity tag by thrombin cleavage . A complete data set to 2.3 A resolution was collected using synchrotron radiation . The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 104.3, b = 137.6, c = 142.1 A and 12 molecules in the asymmetric unit.

Eur J Radiol, 2002 Oct, 44(1), 1 - 4
Purulent meningitis with unusual diffusion-weighted MRI findings; Abe M et al.; We describe unusual findings obtained by diffusion-weighted magnetic resonance imaging (MRI) in a patient with acute purulent meningitis caused by penicillin-resistant Streptococcus pneumoniae . Along cerebral convexities and the Sylvian fissure, multiple small intense lesions showed high signal intensity in these sequences . This may be the first report of diffusion-weighted in purulent meningitis.

Glob Issues, 1996 Nov, 1(17), 31 - 4
The threat of emerging infections; Skin conditions common to people with HIV infection or AIDS; PIP: The World Health Organization clinical criteria for AIDS diagnosis in Africa include Kaposi's sarcoma, Herpes zoster, Herpes simplex, and pruritic maculopapular rash, which have a predictive value for HIV seropositivity of 71-98% . Skin conditions may be classified as: 1) generalized dermatitis, 2) bacterial, fungal, viral, and parasitic infections, and 3) skin tumors . Pruritic maculopapular rash (prurigo) is often the first outward sign of HIV infection . Soothing preparations such as calamine lotion or E45 emollient cream can be applied . Occasionally antihistamine may be necessary, e.g., 10 mg of chlorpheniramine 8 hourly . Skin lesions may become secondarily infected with bacteria; usually Staphylococcus aureus and Streptococcus species . Persistent folliculitis or carbuncles should be treated with flucloxacillin 250 mg QDS for 7 days . In HIV/AIDS fungal infections often develop secondary infection . Candidiasis (thrush) is caused by yeasts, mainly Candida albicans and a small percentage by Tolurosis glabrata . Many HIV-infected patients suffer from seborrheic dermatitis . Fungal diseases more typically present as ringworms of the scalp (Tinea capitis) . Whitfield's ointment is effective for ringworm . Antifungal creams such as miconazol or clotrimazole and systemic antifungal tablets such as ketoconazole, fluconazole, and itraconazole are also effective . Gentian violet lotion twice daily and Acyclovir tablets, 200 mg 5 times daily for 5 days, may help to reduce secondary Herpes simplex infection . HIV has been associated with an increased incidence of Herpes zoster (shingles) . It is often necessary to give analgesics like aspirin or paracetamol to control the pain . Gentian violet paint may help to prevent secondary infection . When shingles affects the eye, Acyclovir tablets (800 mg 5 times daily) should be given . Kaposi's sarcoma affects wider age groups, and it is disseminated and more aggressive than the endemic type . Treatment options include radiotherapy and systemic cytotoxics such as vincristine . Intralesional injections of the drug interferon have also given successful results with some patients .

Medicina (B Aires), 2002, 62(4), 337 - 8
{Severe polyarthritis and tenosynovitis due to Streptococcus agalactiae in a patient with functional hyposplenia}; Balderramo DC et al.; Cases of arthritis caused by Streptococcus agalactiae are infrequent and in our knowledge there are no case reports of tenosynovitis caused by S . agalactiae . A 46-year-old woman presented with fever, polyarthralgia, myalgia, diarrhea and vomiting . She had a history of papillary thyroid carcinoma and functional hyposplenia . She was febrile, with arthritis in hands, wrists, elbows, right shoulder and left ankle joints, and presented tenosynovitis in both feet and left hand . Blood and right olecranon bursa sample cultures were positive for S . agalactiae . An ultrasound scan made at the musculus tibialis anterior of left foot revealed signs of tenosynovitis . She was treated with intravenous cefazolin for 20 days and oral cefuroxime for 12 days . The joint involvement completely subsided in 60 days . Streptococcus agalactiae can cause, infrequently, a polyarthritis and tenosynovitis syndrome similar to disseminated gonococcal infection.

Curr Opin Pharmacol, 2002 Oct, 2(5), 493 - 500
Ketolides: the future of the macrolides?
Nilius AM, Ma Z.
The prevalence of antibiotic resistance in bacterial pathogens associated with community-acquired respiratory tract infections is increasing . Ketolides, semi-synthetic derivatives of erythromycin, overcome the macrolide resistance mechanisms found in Streptococcus pneumoniae and Streptococcus pyogenes, two key pathogens . They also have improved potency and longer post-antibiotic effects, while maintaining the antibacterial spectrum of the macrolide class . The new ketolides cethromycin (ABT-773) and telithromycin have overall antibacterial properties that suggest they will be clinically useful new antibiotics and are undergoing clinical development and regulatory review.

EPI Newsl . 1998 Apr;20(2):4.
Central America meeting initiates surveillance system for Hib and Streptococcus pneumoniae; A pneumococcal vaccine to save children of all ages nears final testing; PIP: Streptococcus pneumoniae is responsible for many of the cases of bacterial blood infection, meningitis, and pneumonia which cause the deaths of more than 1 million children annually in the developing world . It is therefore, second to measles, the developing world's single most devastating cause of child mortality . 10 years ago, the National Academy of Sciences and the National Institutes of Health rated a pneumococcal vaccine for young children the top priority vaccine for least developed countries . Efforts need to be stepped up to produce a good pneumococcal vaccine, especially since the only vaccine currently available is largely ineffective in infants . The technology exists to produce such a vaccine, its clinical development is under way, and there are strong chances of soon realizing its creation and application in the field . A long list of clinical trials of pneumococcal conjugate vaccines for young children is presented .

Int J Antimicrob Agents, 2002 Aug, 20(2), 141 - 3
Stabilization of penicillin resistance among Streptococcus pneumoniae isolated in Eastern Tennessee; Baddour LM et al.; Penicillin resistance among Eastern Tennessee isolates of Streptococcus pneumoniae has been increasing since the early 1990s . To maintain active surveillance of the prevalence of penicillin resistance among pneumococci isolated at our institution, antibiotic susceptibility testing was performed for 95 consecutive isolates and results were compared with those of strains examined 2 years earlier . The prevalence of penicillin resistance among local pneumococcal isolates may have stabilized in recent years.

Int J Antimicrob Agents, 2002 Aug, 20(2), 136 - 40
In vitro activity of ertapenem (MK-0826) against multi-drug resistant Streptococcus pneumoniae compared with 13 other antimicrobials; Hilliard NJ et al.; We tested ertapenem (MK-0826), a new carbapenem, and 13 other antimicrobials by microbroth dilution against 102 isolates of Streptococcus pneumoniae, selected to include organisms resistant to a variety of drug classes . Ertapenem MICs ranged from < or =0.008 to 4 mg/l, MIC(50)=0.5 mg/l, and MIC(90)=2 mg/l . Based on MIC(90), ertapenem potency was 4-fold greater than cefuroxime, 2-fold greater than amoxycillin/clavulanate, =penicillin, 2-fold less than meropenem and ceftriaxone, and 4-fold less than imipenem . Other drug classes including macrolides, tetracycline and fluoroquinolones were less potent overall than the carbapenems . Linezolid (MIC(90)=1 mg/l) was the only agent tested for which all isolates were fully susceptible . Activity of ertapenem decreased as MICs to penicillins, cephalosporins, other carbapenems and macrolides increased . Isolates resistant to clindamycin, tetracycline or fluoroquinolones showed no obvious decrease in ertapenem activity when compared with susceptible isolates with the majority of isolates resistant to these drug classes inhibited by ertapenem at concentrations less than 1 mg/l . Ertapenem may prove useful as an alternative to ceftriaxone and other agents in the treatment of community-acquired pneumonia (CAP) due to S . pneumoniae, including infections caused by organisms with reduced susceptibilities to other antimicrobial agents.

Int J Antimicrob Agents, 2002 Aug, 20(2), 119 - 29
The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults; Petitpretz P et al.; This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults . The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l . A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients) . The most common pathogen isolated was S . pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group) . In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4) . The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively . The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85% . Both regimens were well tolerated, with no differences in adverse events between the groups . Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S . pneumoniae strains with high-level penicillin resistance.

Int J Antimicrob Agents, 2002 Aug, 20(2), 113 - 8
Clinical aspects and cost of invasive Streptococcus pneumoniae infections in children: resistant vs . susceptible strains; Quach C et al.; Invasive Streptococcus pneumoniae infections in children are associated with serious consequences in terms of morbidity and mortality . The main objective of the study was to determine if invasive infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP) differed in clinical presentation, outcome, risk factors, or cost from those caused by penicillin-susceptible strains (PSSP) in children . All patients aged 18 or less with invasive Streptococcus pneumoniae infections admitted to two teaching hospitals in Montreal between 1989 and 1998 were included in the study . We present a case-control study in which for each index case of PRSP, 3 controls with PSSP infections were matched for age, sex, and site of infection . One hundred and forty-four patients were included in the analysis (36 cases, 108 controls) . There was no difference between the two groups in terms of initial clinical presentation (vital signs, laboratory results) or total length of stay . Mortality was 2.7% in both groups . Hospital antibiotic cost was higher in the PRSP group (211 Canadian dollars (CAD) vs . 74 CAD; P=0.02) . Antibiotic consumption in the preceding month was significantly associated with PRSP infection . Underlying diseases or day-care attendance were not shown to be significant risk factors for acquiring invasive PRSP infection . There were no differences between invasive infections caused by PRSP and PSSP in terms of clinical presentation, morbidity or mortality in a paediatric population.

Int J Antimicrob Agents, 2002 Aug, 20(2), 108 - 12
Macrolide resistance phenotypes in Streptococcus pneumoniae in Santiago, Chile; Palavecino EL et al.; The mechanism of resistance was investigated in 39 macrolide-resistant clinical isolates of Streptococcus pneumoniae isolated from January 1997 to July 1999 in Santiago, Chile . Our results showed that 22 (56.5%) were macrolide-resistant, clindamycin-susceptible isolates (M phenotype) and 17 (43.5%) were macrolide and clindamycin resistant (MLS(B) phenotype) . mefE gene was detected in all M phenotype, while ermB gene was detected in all MLS(B)-phenotype strains . Serotype 14 was the most frequent serotype among M-phenotype strains, and serotypes 19 and 23F were the most frequent serotypes in MLS(B) strains . These results demonstrate that both phenotypes of macrolide-resistant S . pneumoniae are found in Santiago, Chile, with the M phenotype predominating.

Int J Antimicrob Agents, 2002 Aug, 20(2), 100 - 7
Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999-2000; Critchley IA et al.; During 1999-2000, 5015 isolates were collected from 13 countries and tested against levofloxacin . Overall, levofloxacin resistance minimum inhibitory concentration (MIC>or =8 mg/l) was found in 40 isolates (0.8%) . The highest resistance rates were in Hong Kong (8.0%), China (3.3%) and Spain (1.6%) . Levofloxacin retained an MIC(90) of 1 mg/l in all countries . Pulsed-field gel electrophoresis analysis of resistant isolates demonstrated the presence of clones in countries where levofloxacin resistance exceeded 1%, suggesting that the elevated resistance rates could result from resistant clones within participating hospitals . DNA-sequence analysis of the quinolone-resistance-determining regions of gyrA, gyrB, parC and parE genes showed that the most common mutations were in GyrA (Ser81Phe), ParC (Ser79Phe, Lys137Asn) and ParE (Ile460Val), accounting for 40% of the isolates tested . Levofloxacin-resistant isolates were generally non-susceptible to other fluoroquinolones tested . Future studies to characterise resistant isolates by other molecular methods may ensure that the appropriate counter-measures can be taken to control the spread of resistant isolates.

Int J Antimicrob Agents, 2002 Aug, 20(2), 93 - 9
Single and multi-step resistance selection study in Streptococcus pneumoniae comparing ceftriaxone with levofloxacin, gatifloxacin and moxifloxacin; Browne FA et al.; Attempts were made to select resistant pneumococcal mutants by sequential subculturing of 12 clinically isolated pneumococci, {four were penicillin sensitive (MIC) 0.03-0.06 mg/l, four penicillin intermediate (MIC 0.25-0.5 mg/l) and four penicillin resistant (MIC 2-4 mg/l)} in sub-inhibitory concentrations of ceftriaxone, levofloxacin, gatifloxacin and moxifloxacin . Subculturing in gatifloxacin, levofloxacin, moxifloxacin and ceftriaxone selected 12 mutants (12/12), 10 mutants (10/12), 10 mutants (10/12) and three mutants (3/12), respectively . DNA sequencing of the quinolone-resistant mutants showed that most strains had mutations in GyrA at E85 or S81 . This in vitro mutation study demonstrates a clear distinction between the low frequency of development of resistance with ceftriaxone exposure as opposed to the high frequency with quinolone exposure.

Int J Antimicrob Agents, 2002 Aug, 20(2), 86 - 92
Antimicrobial susceptibility and serotypes of nasopharyngeal Streptococcus pneumoniae in children with pneumonia and in children attending day-care centres in Fortaleza, Brazil; Rey LC et al.; The susceptibility of nasopharyngeal Streptococcus pneumoniae to eight antibiotics was studied in 482 children under 5 years of age with community-acquired pneumonia and in 429 healthy pneumococci carriers in Fortaleza, Brazil . Serotyping of strains with pooled and type-specific antisera was also performed . Overall, S . pneumoniae was isolated from 499/911 (55%) children . The carriage rate in children attending day-care centres was higher (72%) than in children with pneumonia (50%) (P<0.001) . MIC determination in 441 strains revealed 45% to be intermediate penicillin-resistant and 4% high penicillin-resistant strains . Resistance rates to co-trimoxazole and erythromycin were 42 and 23%, respectively . Serotyping of 211 penicillin-resistant and 58 randomly selected penicillin-susceptible isolates showed that 78% of the strains belonged to paediatric serogroups 6, 14, 19 and 23 (86% of the penicillin-resistant and 51% of the penicillin-susceptible strains, P=0.001) . Resistance rates of S . pneumoniae to penicillin and co-trimoxazole in Fortaleza were higher than previously reported in Brazil and associated with paediatric serogroups 6, 14, 19 and 23.

J Med Assoc Thai, 2002 Jul, 85(7), 839 - 41
Streptococcus sanguis meningitis: report of a case; Chotmongkol V et al.; A 35-year-old woman who presented with acute purulent meningitis and hearing loss was reported . No bacteria was seen with Gram' s stain of cerebrospinal fluid (CSF) . CSF grew Streptococcus viridans, which was subsequently identified to be S . sanguis . The patient improved after treatment, including hearing.

J Med Assoc Thai, 2002 Jul, 85(7), 778 - 81
The masticator space infection; Srirompotong S et al.; The masticator space is an important suprahyoid tissue compartment . Infection of the masticator space can break through the fascia and involve the adjacent space . Severe complications including mediastinitis, pericarditis and death have been reported . The correct diagnosis and proper management are, therefore, crucial in order to reduce this complication . The authors reviewed 22 patients with masticator space infection between July 1996 and June 2001 . All of the patients presented with trismus and 18 patients (81.8%) had a suspected dental cause of infection . Five patients had underlying disease; three were diabetic and two had human immunodeficiency virus (HIV) infection . High dosage intravenous antibiotics directed towards the causative microorganism were given to all of the patients . Fourteen patients underwent surgical drainage and surgical drain was positive in eleven patients (78.5%) . Routine aerobic cultures were done on samples of the drained material . Bacteriology showed Streptococcus spp . the dominant microorganism in three patients, Pseudomonas spp . in one patient and no growth in ten patients . Blood culture grew Burholderia pseudomallei in one patient who responded to medical treatment . Three patients had post-operative complications but all recovered.

Egypt Popul Fam Plann Rev, 1976 Jun, 9(1), 1 - 6
Bacterial flora of the endometrial cavity with intrauterine contraceptive devices; Elkholi GD et al.; PIP: A series of sterilization patients were studied to determine the effect of an IUD (Lippes Loop) on the bacterial flora of the endometrial cavity in Egyptian females . Nearly all were aged 35-42 with parity of 5-14 labors, and low to moderate socioeconomic status . 22 patients were wearing a loop inserted 6-18 months previously by a family planning center . 7 patients were wearing no loop but agreed to wear a loop inserted after 4 weeks of treatment with chloramphenicol; the loops were worn for 6 months . A 3rd group received chloramphenicol treatment but no loop . The 4th group was a control . Technique used to take samples during vaginal surgical sterilization is described . Cultures were incubated and studied . The patients wearing the IUD inserted by the family planning agency showed positive cultures both for the cervix and the uterine cavity . Isolates included Staphylococcus albus and streptococcus pyogenes (3 cases), streptococcus pyogenes and coliform (2 cases), streptococcus pyogenes (1 case), and staphyloccoccus albus (1 case) . No growth was obtained from the women treated with chloramphenicol . In the control group all cervical cultures were positive while only 2 endometrial cultures were positive; detected were streptococcus pyogenes and staphylococcus albus . All were sensitive to standard antibiotics . Routine introduction of the loop through the cervix without antibiotic treatment seemed to transfer cervical flora to the endometrial cavity as the organisms isolated from both organs were identical in the same patient .

Nurs Stand, 2002 Sep 11-17, 16(52), 39 - 42
Nursing management of necrotising fasciitis; Gully S; Necrotising fasciitis is a soft tissue infection often caused by two or more bacteria, most commonly Group A streptococcus bacteria . This article provides an overview of the symptoms, treatment and nursing care of patients with necrotising fasciitis . Psychosocial considerations, public perceptions, consent and advocacy are also discussed.

Clin Oral Investig, 2002 Sep, 6(3), 166 - 70 Epub 2002 Aug 16.
In vitro study of transmission of bacteria from contaminated metal models to stone models via impressions; Sofou A et al.; The purpose of this study was to determine the risk of microbiological transmission into the dental laboratory via impressions and dental stone models . Metal master models were contaminated with Bacillus subtilis and Streptococcus sanguis . Impressions in alginate, polyvinylsiloxane, and polyether were used, and models were cast in two brands of dental stone . Samples were taken from the impression surfaces before and after casting, and sections from the stone models were taken by a technique developed for this study . After incubation, the numbers of colonies were counted and the numbers of colony-forming units per milliliter were calculated . The reductions were statistically significant but considered to be clinically insignificant . The conclusion is that even after severe contamination, the risks to dental laboratory personnel are minimal . "Normal" hygienic procedures are recommended instead of disinfection.

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