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