Streptococcal

SADJ, 1999 Oct, 54(10), 464 - 9
The effect of elastomeric impression materials on the growth of micro-organisms; Tuit CM et al.; The influence of elastomeric impression materials on the growth of micro-organisms was examined in vitro . Bacillus subtilis was inoculated into broth containing impression materials and incubated at 37 degrees C for 72 hours . Express STD Putty, President Putty and Jet-Light Body, Low and Very High Viscosity Permagum and Provil L stimulated growth whereas Impregum-F and Express Light Body inhibited growth . The influence of Impregum-F and Express Light Body on oral micro-organisms was investigated further . Broth extracts were prepared by soaking these materials in Todd Hewitt broth for either 5 or 10 minutes . Thereafter, the extracts were inoculated with oral strains of Staphylococcus aureus, Streptococcus mutans and Candida albicans, incubated at 37 degrees C for 72 hours and plated on blood and Sabourauds agar to test for the presence of viable micro-organisms . The 10-minute broth extracts killed all the test isolates which suggests that impressions taken with Impregum-F and Express Light Body may not require disinfecting.

Heart, 2000 Jul, 84(1), 25 - 30
Infective endocarditis: clinical spectrum, presentation and outcome . An analysis of 212 cases 1980-1995; Netzer RO et al.; OBJECTIVE: To evaluate recent changes in the spectrum and clinical presentation of infective endocarditis and to determine predictors of outcome . DESIGN: A retrospective case study . METHODS: Demographic, clinical, and echocardiographic characteristics were examined in 212 patients who fulfilled the Duke criteria for infective endocarditis between January 1980 and December 1995 to assess changes in clinical presentation and survival . RESULTS: Clinical presentation and course did not change significantly during the study period despite the concurrent introduction of new diagnostic tools (for example, transoesophageal echocardiography) . In-hospital mortality was 15% and remained unchanged . Neurological symptoms on admission, arthralgia, and weight loss were all independent risk factors for adverse outcome (odds ratios 26.1, 6.2, and 4.2, respectively) . Age, prosthetic valve disease, previous antibiotic treatment, renal insufficiency, surgical treatment, and the type of valve involved were not predictive of mortality . In contrast to all other major reports, Streptococcus viridans was the most common causative organism in intravenous drug users (52%) . CONCLUSIONS: Despite the introduction of new diagnostic tools, the course of infective endocarditis has remained unchanged over a period of 16 years . Evidence of early dissemination of the disease to other sites was associated with adverse outcome . Even in elderly patients, early aggressive treatment seems to be effective.

Arch Mal Coeur Vaiss, 2000 May, 93(5), 631 - 4
{Osler endocarditis of a ventricular septal defect in a 21-month old child}; Legendre A et al.; The authors report a case of streptococcus mitis endocarditis of a ventricular septal defect in a 21 months old girl admitted for necrotic purpura of the lower limbs and a history of general ill health and pyrexia for two months . The severity of this case of endocarditis was illustrated by the importance of the vasculitis, the biological signs of infection (disseminated intravascular coagulation), and the size of the vegetation . The vegetation extended from the tricuspid valve as far as the pulmonary orifice which was partially obstructed, causing signs of right ventricular failure . The portal of entry was not found . Surgical ablation of the vegetation with tricuspid valvuloplasty was necessary after 48 hours of antibiotherapy . The outcome after one year's follow-up is good . The diagnosis of bacterial endocarditis must be considered even in very young children, especially those with congenital heart disease, and, in particular, ventricular septal defect.

Antimicrob Agents Chemother, 2000 Jul, 44(7), 1803 - 8
IB-367, a protegrin peptide with in vitro and in vivo activities against the microflora associated with oral mucositis; Mosca DA et al.; Although the microflora associated with oral mucositis initiated by cytotoxic therapy is not well characterized, several studies suggest that reduction of the microbial load in the oral cavity has some clinical benefit . The MICs of IB-367, a synthetic protegrin analog, ranged from 0.13 to 64 microgram/ml for gram-positive bacteria (Streptococcus mitis, Streptococcus sanguis, Streptococcus salivarius, and Staphylococcus aureus) and from 0.06 to 8 microgram/ml for gram-negative species (Klebsiella, Escherichia, and Pseudomonas) . IB-367 exhibited rapid, microbicidal activity against both log- and stationary-phase cultures of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa . At concentrations near the MICs for these two organisms (4 and 2 microgram/ml, respectively), IB-367 reduced viability by more than 3 logs in less than 16 min . Similarly, IB-367 effected a 4-log reduction of the endogenous microflora in pooled human saliva within 2 min at 250 microgram/ml, a concentration readily attained by local delivery . After nine serial transfers at 0.5x the MIC, the MIC of IB-367 for MRSA and P . aeruginosa increased only two to four times . In a phase I clinical study with healthy volunteers, IB-367 was well tolerated, with no detectable systemic absorption . One hour after treatment with 9 mg of IB-367, the prevalence of gram-negative bacteria and yeast was reduced, and the density of the predominant gram-positive oral flora was decreased 1,000 times . IB-367's properties (speed of killing, breadth of spectrum, and lack of resistance) make the compound a strong candidate for the prophylaxis of oral mucositis . Phase II clinical trials with IB-367 are under way for this indication in immunocompromised subjects.

Infect Immun, 2000 Jul, 68(7), 4180 - 8
The putative proteinase maturation protein A of Streptococcus pneumoniae is a conserved surface protein with potential to elicit protective immune responses; Overweg K et al.; Surface-exposed proteins often play an important role in the interaction between pathogenic bacteria and their host . We isolated a pool of hydrophobic, surface-associated proteins of Streptococcus pneumoniae . The opsonophagocytic activity of hyperimmune serum raised against this protein fraction was high and species specific . Moreover, the opsonophagocytic activity was independent of the capsular type and chromosomal genotype of the pneumococcus . Since the opsonophagocytic activity is presumed to correlate with in vivo protection, these data indicate that the protein fraction has the potential to elicit species-specific immune protection with cross-protection against various pneumococcal strains . Individual proteins in the extract were purified by two-dimensional gel electrophoresis . Antibodies raised against three distinct proteins contributed to the opsonophagocytic activity of the serum . The proteins were identified by mass spectrometry and N-terminal amino acid sequencing . Two proteins were the previously characterized pneumococcal surface protein A and oligopeptide-binding lipoprotein AmiA . The third protein was the recently identified putative proteinase maturation protein A (PpmA), which showed homology to members of the family of peptidyl-prolyl cis/trans isomerases . Immunoelectron microscopy demonstrated that PpmA was associated with the pneumococcal surface . In addition, PpmA was shown to elicit species-specific opsonophagocytic antibodies that were cross-reactive with various pneumococcal strains . This antibody cross-reactivity was in line with the limited sequence variation of ppmA . The importance of PpmA in pneumococcal pathogenesis was demonstrated in a mouse pneumonia model . Pneumococcal ppmA-deficient mutants showed reduced virulence . The properties of PpmA reported here indicate its potential for inclusion in multicomponent protein vaccines.

Infect Immun, 2000 Jul, 68(7), 3949 - 55
Selection of recombinant antibodies specific for pathogenic Streptococcus suis by subtractive phage display; de Greeff A et al.; A semisynthetic antibody phage display library was used to select recombinant antibodies directed against surface components of a pathogenic strain of Streptococcus suis serotype 2 and against extracellular factor (EF), a protein known to be exclusively associated with pathogenic S . suis serotype 2 strains . Three distinct monoclonal phage antibodies directed against conformational epitopes of surface protein components of S . suis were selected . In addition, three different monoclonal phage antibodies were isolated that recognized EF . To isolate antibody fragments that recognize epitopes specific for a pathogenic S . suis serotype 2 strain, compared to a nonpathogenic serotype 2 strain, we applied a subtractive selection procedure . With this procedure, only one distinct phage antibody was found, and it was shown to be directed against EF . This demonstrates the selectivity of the applied procedure and confirms that EF is indeed differentially expressed by pathogenic and nonpathogenic strains . It also shows that EF is a very dominant antigen in phage antibody selections.

Curr Microbiol, 2000 Aug, 41(2), 106 - 8
Variation in sic gene encoding complement-inhibiting protein of Streptococcus pyogenes serotype M1 isolates in Japan; Murase T et al.; DNA sequencing of the gene encoding a complement-inhibiting protein of Streptococcus pyogenes (streptococcal inhibitor of complement, Sic) was carried out on 49 strains of S . pyogenes serotype M1 . Those strains were obtained from patients and asymptomatic carriers in Japan from 1969 to 1997 and had various pulsed-field gel electrophoresis (PFGE) patterns . Four identical polymorphic sites were found in the strains with the same PFGE pattern (Ia), but not in those giving the pattern IIa . The other identical sites were found in the strains with the PFGE pattern IIa, but not in those with the pattern Ia . These observations suggest that each of PFGE patterns was restricted to a set of variation in the sic gene.

J S Afr Vet Assoc, 1999 Dec, 70(4), 156 - 7
Teat lesions and their relationship to intramammary infections on small-scale dairy farms in Kiambu district in Kenya; Mulei CM; Mammary gland quarters of 139 lactating dairy cows from small-scale dairy herds were examined visually and by palpation for teat lesions and by California mastitis test (CMT) and bacterial culture for subclinical mastitis . Teat lesions were observed in 97 teats . These included teat chaps (39.2%), teat papillomas (23.7%), teat erosions (22.7%), teat fistulae (5.1%), inverted teats (5.1%) and blocked teats (4.2%) . According to the CMT, the prevalence of subclinical mastitis was 33.4% in all the mammary gland quarters, 71.0% in quarters with teat lesions and 24.5% in quarters without teat lesions . There was a significant (P < 0.01) association between teat lesions and the prevalence of subclinical mastitis . The mammary gland quarters with teat lesions were 7.2 times more likely to have a positive CMT (P < 0.01) and 5.6 times more likely to have bacterial organisms (P < 0.01) isolated from them than those without any teat lesions . The bacterial organisms most frequently isolated from the CMT-positive milk samples from both the mammary gland quarters with teat lesions and those without teat lesions were Staphylococcus aureus (50.0%), Streptococcus spp . (34.8%) and Arcanobacterium pyogenes (6.2%).

J S Afr Vet Assoc, 1999 Jun, 70(2), 98 - 9
Streptococcus phocae infections associated with starvation in Cape fur seals; Henton MM et al.; Mortalities and abortions associated with starvation occurred at Cape Cross, Namibia, in Cape fur seals (Arctocephalus pusillus pusillus) . Affected seals showed lethargy and emaciation, and the most common pathological signs were those of a respiratory infection, both in adults and offspring . Streptococcus phocae was isolated from adult seals, a cub and aborted foetuses.

J Biol Chem, 2000 Aug 25, 275(34), 25972 - 8
Biosynthesis of type 3 capsular polysaccharide in Streptococcus pneumoniae . Enzymatic chain release by an abortive translocation process; Forsee WT et al.; The type 3 polysaccharide synthase from Streptococcus pneumoniae catalyzes sugar transfer from UDP-Glc and UDP-glucuronic acid (GlcUA) to a polymer with the repeating disaccharide unit of {3)-beta-d-GlcUA-(1-->4)-beta-d-Glc-(1-->} . Evidence is presented that release of the polysaccharide chains from S . pneumoniae membranes is time-, temperature-, and pH-dependent and saturable with respect to specific catalytic metabolites . In these studies, the membrane-bound synthase was shown to catalyze a rapid release of enzyme-bound polysaccharide when either UDP-Glc or UDP-GlcUA alone was present in the reaction . Only a slow release of polysaccharide occurred when both UDP sugars were present or when both UDP sugars were absent . Chain size was not a specific determinant in polymer release . The release reaction was saturable with increasing concentrations of UDP-Glc or UDP-GlcUA, with respective apparent K(m) values of 880 and 0.004 micrometer . The apparent V(max) was 48-fold greater with UDP-Glc compared with UDP-GlcUA . The UDP-Glc-actuated reaction was inhibited by UDP-GlcUA with an approximate K(i) of 2 micrometer, and UDP-GlcUA-actuated release was inhibited by UDP-Glc with an approximate K(i) of 5 micrometer . In conjunction with kinetic data regarding the polymerization reaction, these data indicate that UDP-Glc and UDP-GlcUA bind to the same synthase sites in both the biosynthetic reaction and the chain release reaction and that polymer release is catalyzed when one binding site is filled and the concentration of the conjugate UDP-precursor is insufficient to fill the other binding site . The approximate energy of activation values of the biosynthetic and release reactions indicate that release of the polysaccharide occurs by an abortive translocation process . These results are the first to demonstrate a specific enzymatic mechanism for the termination and release of a polysaccharide.

Arerugi, 2000 May, 49(5), 412 - 9
{Chlamydia pneumoniae infection in patients with acute bronchitis and bronchial asthma}; Oshima M et al.; In this study, a total of 60 patients with acute bronchitis, 71 patients with bronchial asthma and 20 healthy volunteers were serologically and bacteriologically analyzed to investigate whether Chlamydia pneumoniae infection is associated with the onset and the exacerbation with acute bronchitis and bronchial asthma . Antibody titers to Chlamydia pneumoniae were also measured and compared by ELISA method . The antibody-positive rate in the patients with acute bronchitis (88.4%) was significantly higher than that in the patients with bronchial asthma (73.3%) or that in the healthy volunteers (60%) . And the levels of the IgA antibody in the patients with acute bronchitis were significantly higher than those in the patients with bronchial asthma or those in the healthy volunteers . The rate of acute C . pneumoniae infection in the patients with acute bronchitis (20%) did not show significantly differences compared with that in the patients with bronchial asthma (15.5%) or that in the healthy volunteers (10%) . The cases of acute C . pneumoniae infection had both as a single etiologic agent and as a mixed infection, most often with Streptococcus pneumoniae . Therefore, we demonstrated that the acute C . pneumoniae infection may be associated with the onset and the exacerbation in acute bronchitis and bronchial asthma.

J Bacteriol, 2000 Jun, 182(12), 3353 - 60
Hyperrecombination in Streptococcus pneumoniae depends on an atypical mutY homologue; Samrakandi MM et al.; The unusual behavior of the mutation ami36, which generates hyperrecombination in two point crosses, was previously attributed to a localized conversion process changing A/G mispairs into CG pairs . Although the mechanism was found to be dependent on the DNA polymerase I, the specific function responsible for this correction was still unknown . Analysis of the pneumococcal genome sequence has revealed the presence of an open reading frame homologous to the gene mutY of Escherichia coli . The gene mutY encodes an adenine glycosylase active on A/G and A/7,8-dihydro-8-oxoguanine (8-OxoG) mismatches, inducing their repair to CG and C/8-OxoG, respectively . Here we report that disrupting the pneumococcal mutY homologue abolishes the hyperrecombination induced by ami36 and leads to a mutator phenotype specifically enhancing AT-to-CG transversions . The deduced amino acid sequence of the pneumococcal MutY protein reveals the absence of four cysteines, highly conserved in the endonuclease III/MutY glycosylase family, which ligate a {4Fe-4S}(2+) cluster . The actual function of this cluster is still intriguing, inasmuch as we show that the pneumococcal gene complements a mutY strain of E . coli.

Am J Respir Crit Care Med, 2000 Jun, 161(6), 2043 - 50
Differential patterns of apoptosis in resolving and nonresolving bacterial pneumonia; Kazzaz JA et al.; Infection with either Streptococcus sanguis or Streptococcus pneumoniae type 25 causes acute pneumonitis in rats . Pneumonia caused by S . sanguis resolves over the course of 8 d, whereas pneumonia caused by S . pneumoniae type 25 progresses to fibrosis . To examine the role of apoptosis in these models, we performed assays with the terminal deoxynucleotidyltransferase-uridine nucleotide end-labeling technique on tissue sections from rat lungs at various times, and quantified the results with image analysis . Apoptosis was a feature of both the acute and resolving stages of pneumonia . The pattern and extent of apoptosis were similar in both models during the acute stage, and the number of apoptotic nuclei increased in both models through 4 d after infection . Although there were differences in the cellular pattern of apoptosis after 2 d and 4 d of infection, the extent of apoptosis was the same in both models . After 8 d, major differences were observed . In the resolving model, apoptosis was limited primarily to an abscess in the base of the lung . In the nonresolving model, apoptosis was persistent . We also found that cyclin-dependent kinase-5 expression is upregulated during apoptosis induced by bacterial infection . These data indicate that the location and timing of apoptosis may determine whether pneumonia resolves or progresses to fibrosis.

Laryngoscope, 2000 Jun, 110(6), 1050 - 5
Sinus tissue pharmacokinetics after oral administration of amoxicillin/clavulanic acid; Dinis PB et al.; OBJECTIVES: The in vitro synergy of the amoxicillin/clavulanic acid combination has not always translated in vivo into clinical superiority compared with amoxicillin alone . Specifically, conflicting reports have disputed the superiority of the combination in the treatment of both acute otitis media and acute sinusitis . One possible reason for this may have to do with inadequate target tissue pharmacokinetics . To explore this possibility in the sinuses, we undertook the present investigation . STUDY DESIGN: A randomized, open, single-dose, sinus tissue pharmacokinetic study with oral amoxicillin/clavulanic acid . METHODS: Twenty-three adult patients with chronic rhinosinusitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amoxicillin/clavulanate 2 to 4 hours before surgery began . During the operation tissue samples were collected at specific sinonasal sites for determination of both amoxicillin and clavulanic acid concentration levels . RESULTS: Amoxicillin displayed adequate tissue levels throughout the sinuses, high enough to cover common susceptible pathogens . However, the presence of clavulanate was detected in only half of the sinonasal tissue samples . CONCLUSIONS: The kinetics of oral clavulanic acid apparently fails to provide a widespread anti-beta-lactamase activity capable of enhancing the activity of amoxicillin in all parts of the sinuses . Despite this, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective oral beta-lactam against Streptococcus pneumoniae, a particularly virulent and increasingly resistant upper respiratory tract pathogen . Also, as our data show, a concomitant anti-beta-lactamase activity can be expected to occur, although in an unpredictable fashion.

Laryngoscope, 2000 Jun, 110(6), 969 - 71
Bacteriology of nontraumatic maxillary sinus mucoceles versus chronic sinusitis; Busaba NY et al.; OBJECTIVE: To compare the bacteriology of maxillary sinus mucoceles to chronic sinusitis and understand the pathogenesis of nontraumatic maxillary sinus mucoceles (NTMSM) . STUDY DESIGN: Retrospective review . METHODS: Review of intraoperative bacteriology culture results obtained in patients with NTMSM . Patients with history of facial trauma or previous paranasal sinus surgery were not included in the study . The results were compared to intraoperative cultures obtained from patients with chronic sinusitis (CS) . RESULTS: The study groups consisted of 16 patients with NTMSM (9 male and 7 female patients) and 211 patients with CS (86 male and 125 female patients) . Cultures in the NTMSM group were positive in 7 of 16 patients (44%) (four cultures had more than one isolate) . There was no growth in cultures of 9 patients (56%) . On the other hand, cultures in 176 patients with CS (83%) grew organisms (42 cultures had more than one isolate); there was no growth in 35 of 211 patients (17%) (P = .0007) . The cultures grew aerobic bacteria in 7 of 16 (44%) and 160 of 211 (76%) patients of the NTMSM and CS groups, respectively . Anaerobic bacteria were detected in cultures of 2 of 16 patients (12.5%) with NTMSM compared with 13 of 211 patients (6.2%) in the CS group (P = .286) . The most common pathogenic aerobe in the NTMSM group was alpha-hemolytic Streptococcus, while Staphylococcus aureus was the most common in the CS group . CONCLUSION: The bacteriology of maxillary sinus mucoceles is different from that of CS . The majority of patients with mucoceles have sterile intraoperative cultures . The data do not support infection as the main origin of NTMSM.

J Rheumatol, 2000 Jun, 27(6), 1518 - 20
Association of HLA-DR7 with rheumatic fever in the Brazilian population; Visentainer JE et al.; OBJECTIVE: Rheumatic fever (RF) is a multisystem inflammatory disease that develops as a sequel of untreated throat infection by the group A beta-hemolytic streptococcus . As HLA antigens are known to be important in controlling immunological responsiveness, studies have investigated HLA antigen association with RF . Studies with Caucasians, Black Americans, and Indians showed associations with HLA-DR4, DR2, and DR3, respectively . One study on a Brazilian population suggested an association with HLA-DR7 and HLA-DR53 . We investigated the association between RF and antigens HLA-DR7 and DR53 in the white Brazilian population . METHODS: Thirty-five patients and 209 healthy individuals living in the northern region of the state of Parana, Brazil, were used as test and control groups, respectively . Classical statistical methods were used to compare HLA frequencies between these groups . Results . Data confirmed positive association with HLA-DR7 (46.7 vs . 25.7%; p = 0.015), but not with HLA-DR53 (54.3 vs . 44.5%; p = 0.28) . The relative risk and etiologic fractions were 2.4 and 0.27%, respectively . CONCLUSION: Positive association between HLA-DR7 specificity and RF was observed in the white Brazilian population by 2 independent studies, supporting the hypothesis of the involvement of genetic factors in susceptibility of rheumatic fever.

Antibiot Khimioter, 2000, 45(4), 18 - 21
{A comparative evaluation of the pharmacokinetics of different forms of benzathine benzylpenicillin}; Belov BS et al.; Comparative randomized opened pharmacokinetic evaluation of benzathine benzylpenicillin in three dosage forms was performed . Benzathine benzylpenicillin was used as extencilline (2.4 million U or 1.2 million U, "Rhone-Poulenc Rorer", France) and as bicillin-5 (1.5 million U, "Synthesis" Russia) . 33 patients were included in investigation (23 women and 10 men aged 16-60 years) . 25 persons had verified rheumatism without blood circulation failure signs, 4--had chronic tonsillitis and 4 were healthy volunteers . Benzylpenicillin concentration was estimated by microbiology test in blood samples taken at 1, 3, 24 hours and 7, 14 and 21 days after intramuscular drug injection . After 2.4 million U extencilline injection (12 patients) its concentration, was at the inhibition level for beta-hemolytic streptococcus group A (25 ng/ml) for 3 weeks-period in 83.3 per cent of patients . After 1.2 million U extencilline injection (10 patients) or 1.5 million U bicillin-5 injection (12 patients) the above mentioned concentration was achieved on the 21st day in 30 and 0 per cent of patients respectively . Thus the treatment with benzathine benzylpenicillin at the 1.2 million U dose in the form of extencilline or bicillin-5 doesn't provide adequate antistreptococcal concentration in blood in prolonged period and is not suitable for correct rheumatism prophylaxis in adult patients.

Blood, 2000 Jun 15, 95(12), 3683 - 6
Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants; Kulkarni S et al.; Incidences of and risk factors for Streptococcus pneumoniae sepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997 . SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months) . The infection was fatal in 7 patients . The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively . Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS . Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P =.03) and chronic GVHD (10-year probability, 14% vs 4%; P =.002) were associated with significantly higher risk for SPS . All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127; P =.07) . Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis . None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus . Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16; P =.04) . We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD . Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk . These patients should receive lifelong pneumococcus prophylaxis . Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections . Further studies are required to determine the optimum prophylactic strategy in patients at risk . (Blood . 2000;95:3683-3686)

J Bacteriol, 2000 Jul, 182(13), 3740 - 7
Role of the dpr product in oxygen tolerance in Streptococcus mutans; Yamamoto Y et al.; We have previously identified and characterized the alkyl hydroperoxide reductase of Streptococcus mutans, which consists of two components, Nox-1 and AhpC . Deletion of both nox-1 and ahpC had no effect on the sensitivity of S . mutans to cumene hydroperoxide or H(2)O(2), implying that the existence of another antioxidant system(s) independent of the Nox-1-AhpC system compensates for the deficiency . Here, a new antioxidant gene (dpr for Dps-like peroxide resistance gene) was isolated from the S . mutans chromosome by its ability to complement an ahpCF deletion mutant of Escherichia coli with a tert-butyl hydroperoxide-hypersensitive phenotype . The dpr gene complemented the defect in peroxidase activity caused by the deletion of nox-1 and ahpC in S . mutans . Under aerobic conditions, the dpr disruption mutant carrying a spectinomycin resistance gene (dpr::Spc(r) mutant) grew as well as wild-type S . mutans in liquid medium . However, the dpr::Spc(r) mutant could not form colonies on an agar plate under air . In addition, neither the dpr::Spc(r) ahpC::Em(r)::nox-1 triple mutant nor the dpr::Spc(r) sod::Em(r) double mutant was able to grow aerobically in liquid medium . The 20-kDa dpr gene product Dpr is an iron-binding protein . Synthesis of Dpr was induced by exposure of S . mutans cells to air . We propose a mechanism by which Dpr confers aerotolerance on S . mutans.

J Biol Chem, 2000 Sep 1, 275(35), 26842 - 55
Do sequence repeats play an equivalent role in the choline-binding module of pneumococcal LytA amidase?
Varea J, Saiz JL, Lopez-Zumel C, Monterroso B, Medrano FJ, Arrondo JL, Iloro I, Laynez J, Garcia JL, Menendez M.
LytA amidase breaks down the N-acetylmuramoyl-l-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae . Its polypeptide chain has two modules: the NH(2)-terminal module, responsible for the catalytic activity, and the COOH-terminal module, constructed by six tandem repeats of 20 or 21 amino acids (p1-p6) and a short COOH-terminal tail . The polypeptide chain must contain at least four repeats to efficiently anchor the autolysin to the choline residues of the cell wall . Nevertheless, the catalytic efficiency decreases by 90% upon deletion of the final tail . The structural implications of deleting step by step the two last (p5 and p6) repeats and the final COOH-tail and their effects on choline-amidase interactions have been examined by comparing four truncated mutants with LytA amidase by means of different techniques . Removal of this region has minor effects on secondary structure content but significantly affects the stability of native conformations . The last 11 amino acids and the p5 repeat stabilize the COOH-terminal module; each increases the module transition temperature by about 6 degrees C . Moreover, the p5 motif also seems to participate, in a choline-dependent way, in the stabilization of the NH(2)-terminal module . The effects of choline binding on the thermal stability profile of the mutant lacking the p5 repeat might reflect a cooperative pathway providing molecular communication between the choline-binding module and the NH(2)-terminal region . The three sequence motives favor the choline-amidase interaction, but the tail is an essential factor in the monomer <--> dimer self-association equilibrium of LytA and its regulation by choline . The final tail is required for preferential interaction of choline with LytA dimers and for the existence of different sets of choline-binding sites . The p6 repeat scarcely affects the amidase stability but could provide the proper three-dimensional orientation of the final tail.

Lett Appl Microbiol, 2000 Jun, 30(6), 473 - 8
Anti-adhesive activity of sulphated exopolysaccharides of microalgae on attachment of red sore disease-associated bacteria and helicobacter pylori to tissue culture cells; Guzman-Murillo MA et al.; Because of the affinity of certain bacterial species for sulphated glycoconjugates exposed on the epithelial cells of susceptible hosts, we hypothesized that sulphated exopolysaccharides of microalgae can be used in anti-adhesive therapies against bacterial infections, both in cold- and warm-blooded animals . In this study we found that adhesion of the human pathogen Helicobacter pylori to the HeLa S3 cell line, and adhesion of the fish pathogens Vibrio campbellii, V . ordalii, Streptococcus saprophyticus, and Aeromonas veronii to spotted sand bass primary tissue culture cells, can be effectively blocked with the various sulphated exopolysaccharides used.

J Clin Periodontol, 2000 May, 27(5), 370 - 3
Effect of an essential oil-containing antiseptic mouthrinse on induction of platelet aggregation by oral bacteria in vitro; Whitaker EJ et al.; BACKGROUND: With an increasing body of data suggesting an association between periodontitis and cardiovascular disease, studies have been conducted to elucidate potential mechanisms by which oral bacteria might exert systemic effects . 2 oral bacteria, Streptococcus sanguis and Porphyromonas gingivalis, have been shown to induce platelet aggregation in vitro . This study was conducted to determine the effect of treatment with an essential oil mouthrinse (Listerine Antiseptic) on the platelet-aggregating activity of these organisms . METHOD: Bacteria were grown under standard culture conditions . S . sanguis ATCC strain 10556 was exposed for 3 min to the essential oil mouthrinse at either full strength or a 1:1 dilution, while P . gingivalis FDC strain 381 was exposed to the essential oil mouthrinse at a 1:10 dilution . Positive control cells were treated with Hanks balanced salt solution (HBSS) . Aggregation was measured using a recording platelet aggregometer . The assay of each organism in its respective mouthrinse dilution(s) or HBSS was repeated 5 times . RESULTS: In all cases, the HBSS-treated organisms induced platelet aggregation, with mean(+/-S.E.) lag times of 12.30 (+/-1.36) min and 11.36 (+/-0.58) min for P . gingivalis and S . sanguis, respectively . In contrast, treatment with the essential oil mouthrinse completely inhibited the platelet aggregating activity of P . gingivalis and of S . sanguis exposed to the 1:1 mouthrinse dilution in all assays; the aggregating activity of S . sanguis treated with full-strength mouthrinse was completely inhibited in 4 of 5 assays, and inhibited by 75% in the 5th, for a mean inhibition of 95 +/- 1.5% . CONCLUSION: This study provides additional evidence that the essential oil mouthrinse can interfere with bacterial cell surface-associated activities which may have clinical relevance.

Microbiology, 2000 Jun, 146 ( Pt 6), 1361 - 9
Streptococcus equi with truncated M-proteins isolated from outwardly healthy horses; Chanter N et al.; The M-protein genes of Streptococcus equi isolated from 17 outwardly healthy horses after 4 strangles outbreaks had ended, including a quarantined animal, were compared with those of S . equi isolates from 167 active cases of strangles across 4 countries . The healthy horses included 16 persistent S . equi carriers, at least one from each of the four outbreaks . These carriers, despite being outwardly healthy, had empyema of the guttural pouch(es), an enlargement of the equine Eustachian tube . A persistent carrier from two of these outbreaks, the quarantined animal and a healthy animal with normal guttural pouches, from which S . equi was isolated only once, were colonized by variant S . equi with truncated M-protein genes (24% of outwardly healthy animals with S . equi) . The truncated M-protein genes had in-frame deletions in slightly different positions between the signal sequence and the central repeat region, equivalent to approximately 20% of the mature expressed protein . Immunoblotting with antibody to recombinant M-protein confirmed that the variants expressed a truncated form of the M-protein . In contrast to the outwardly healthy S . equi carriers, only 1/167 of S . equi isolates from strangles cases possessed a truncated M-protein gene (<1%; Fisher's exact test, P=0.0002) . Compared with isolates from healthy horses with a truncated M-protein, much more of the N terminus of the truncated M-protein was retained in the variant S . equi from a strangles case . Variant S . equi from outwardly healthy animals were more susceptible to phagocytosis by neutrophils in vitro than typical isolates . This is the first report of detection of S . equi with a truncated M-protein . The distribution of the variants between strangles cases and carriers suggests that the 80% of the M-protein retained in the variants may contribute to colonization whilst the deleted portion of the gene may be needed for full virulence.

Microbiology, 2000 Jun, 146 ( Pt 6), 1267 - 73
Quantitative detection of Streptococcus pneumoniae cells harbouring single or multiple copies of the gene encoding the green fluorescent protein; Acebo P et al.; A modified gfp gene from Aequorea victoria, encoding a variant of the green fluorescent protein (GFP), was subcloned into the mobilizable plasmid pMV158 . gfp was placed under the control of the inducible P(M) promoter of the Streptococcus pneumoniae gene malM, cloned in plasmid pLS70 . The P(M) promoter is regulated by the product of the pneumococcal malR gene, which is inactivated by growing the cells in maltose-containing media . By homologous recombination, the P(M)-gfp construction was integrated into the host chromosome in a single copy . In both conditions (single and multiple copies), the pneumococcal cells were able to express GFP in an inducible or constitutive form, depending on whether the S . pneumoniae strain harboured a wild-type or a mutant malR gene . Quantification of the levels of GFP expressed by cultures supplemented with sucrose or maltose as carbon sources was feasible by fluorescence spectroscopy . Phase-contrast and fluorescence microscopy allowed pneumococcal cells expressing GFP in mixed cultures to be distinguished from those not carrying the gfp gene.

Mol Microbiol, 2000 May, 36(3), 726 - 36
Species-specific binding of human secretory component to SpsA protein of Streptococcus pneumoniae via a hexapeptide motif; Hammerschmidt S et al.; SpsA, a pneumococcal surface protein belonging to the family of choline-binding proteins, interacts specifically with secretory immunglobulin A (SIgA) via the secretory component (SC) . SIgA and free SC from mouse, rat, rabbit and guinea-pig failed to interact with SpsA indicating species-specific binding to human SIgA and SC . SpsA is the only pneumococcal receptor molecule for SIgA and SC as confirmed by complete loss of SIgA and SC binding to a spsA mutant . Analysis of recombinant SpsA fusion proteins showed that the binding domain is located in the N-terminal region of SpsA . By the use of different truncated N-terminal SpsA fusion proteins, the minimum binding domain was shown to be composed of 112 amino acids (residues 172-283) . The sequence of this 112-amino-acids domain was used to spot synthesize 34 overlapping peptides, consisting of 15 amino acids each, with an offset of three amino acids on a cellulose membrane . One of the peptides reacted specifically with both SIgA and SC . By using a second membrane with immobilized synthetic peptides of decreasing length containing parts of the identified 15-amino-acid motif a hexapeptide, YRNYPT was identified as the binding motif for SC and SIgA . SpsA proteins with a size smaller than the assay-positive domain of 112 amino acids were able to inhibit the interaction of SIgA and pneumococci provided they contained the binding motif . The results indicated that the hexapeptide YRNYPT located in SpsA of pneumococcal strain type 1 (ATCC 33400) between amino acids 198 and 203 is involved in SIgA and SC binding . Because synthetic peptides containing only parts of the hexapeptide also assayed positive, these results further suggest that at least the amino acids YPT of the identified hexapeptide are critical for binding to SC and SIgA . Amino acid substitutions in the identified putative binding motif abolished SC-/SIgA-binding activity of the mutated SpsA protein, confirming the functional activity of this hexapeptide and the critical role of the amino acids YPT in SC and SIgA binding . Identification of this motif, which is highly conserved in SpsA protein among different serotypes, might contribute towards a new peptide based vaccine strategy.

Mol Microbiol, 2000 May, 36(3), 688 - 96
Competence regulation by oxygen in Streptococcus pneumoniae: involvement of ciaRH and comCDE; Echenique JR et al.; Anaerobic aerotolerant Streptococcus pneumoniae modulates its genetic transformability and its virulence in response to the oxygen concentration . The activity of a single protein encoded by nox and showing NADH oxidase activity is involved in these adaptive responses to O2 . Northern blot analysis of wild-type cultures grown under aerobic and microaerobic conditions indicated transcriptional control of comCDE by O2 . An O2-independent mutant strain carrying the gain-of-function mutation comE38KE was isolated and its analysis showed that ComE is a key point in competence stimulation by O2 . Plasmid insertion mutations in ciaRH revealed that this two component signal-transducing system negatively regulates comCDE transcription . The level of comCDE transcripts appears as a major control point in competence regulation by O2 and also by growth phase and cell density.

J Clin Neurosci, 1999 Sep, 6(5), 415 - 418
Polymicrobial brain stem abscess due to Streptococcus anginosus and Actinomyces species; Kalarostaghi AH et al.; This report describes a rare case of a pyogenic brain stem abscess . The lesion was readily identified by computed tomographic (CT) scan and magnetic resonance imaging (MRI) . Streptococcus anginosus was grown from the pus and Actinomyces colonies were found on histopathology . The lesion was successfully treated with stereotactic surgery and antibiotic therapy . A review of the relevant literature including the role of stereotaxy in the treatment of the brain stem abscess is discussed .

Int J Syst Evol Microbiol, 2000 May, 50 Pt 3, 1073 - 9
The Streptococcus anginosus species comprises five 16S rRNA ribogroups with different phenotypic characteristics and clinical relevance; Jacobs JA et al.; A collection of 267 consecutively isolated Streptococcus anginosus strains was screened for the prevalence of previously described 'motile' strains by hybridization with oligonucleotide probes in a reverse line blot assay . The motile strains represented 101 (37.8%) of the S . anginosus strains . The vast majority of these strains fermented mannitol and raffinose, whereas most other S . anginosus strains did not (P<0.001) . Most (83/101) of the motile strains were recovered from the urogenital tract (including five strains from neonatal surveillance cultures) and only a minority (36) of them were associated with infection-related samples (P<0.001) . Strains that hybridized with the same oligonucleotide probes as the type strain S . anginosus ATCC 33397T (= NCTC 10713T) were designated ATCC-like strains . They accounted for 74 (27.7%) of the strains examined, were commonly distributed among the different body parts and were significantly more associated with infection-related samples . Three other hybridization patterns were recognized in the reverse line blot assay, ribogroup I (n = 51), ribogroup II (n = 21) and ribogroup III (n = 19) . Ribogroup II strains were significantly more frequently recovered from the abdominal cavity and were associated with infection-related samples . Ribogroup I included the majority of the S . anginosus strains that carried Lancefield group C . Comparison of the nearly complete 16S rRNA sequence of two representative strains of each ribogroup revealed that all five ribogroups were closely related (>97% sequence similarities), and that most sequence divergences between the ribogroups occurred in the 1024-1064 bp region of the 16S rRNA gene . The present data confirm the heterogeneity within the S . anginosus species.

Biochemistry, 2000 Jun 13, 39(23), 7012 - 23
The first structure of UDP-glucose dehydrogenase reveals the catalytic residues necessary for the two-fold oxidation; Campbell RE et al.; Bacterial UDP-glucose dehydrogenase (UDPGlcDH) is essential for formation of the antiphagocytic capsule that protects many virulent bacteria such as Streptococcus pyogenes andStreptococcus pneumoniae type 3 from the host's immune system . We have determined the X-ray structures of both native and Cys260Ser UDPGlcDH from S . pyogenes (74% similarity to S . pneumoniae) in ternary complexes with UDP-xylose/NAD(+) and UDP-glucuronic acid/NAD(H), respectively . The 402 residue homodimeric UDPGlcDH is composed of an N-terminal NAD(+) dinucleotide binding domain and a C-terminal UDP-sugar binding domain connected by a long (48 A) central alpha-helix . The first 290 residues of UDPGlcDH share structural homology with 6-phosphogluconate dehydrogenase, including conservation of an active site lysine and asparagine that are implicated in the enzyme mechanism . Also proposed to participate in the catalytic mechanism are a threonine and a glutamate that hydrogen bond to a conserved active site water molecule suitably positioned for general acid/base catalysis.

J Infect, 2000 Mar, 40(2), 141 - 4
Carriage of penicillin-susceptible and non-susceptible pneumococci in healthy young children in Göteborg, Sweden; Borres MP et al.; OBJECTIVES: To study carriage of Streptococcus pneumoniae among healthy young children, determine the proportion of strains with decreased susceptibility to penicillin, and study possible risk factors for the carriage of penicillin-resistant strains . METHODS: Between February 1996 and February 1997, 620 healthy, 18-month-old children in Goteborg, Sweden were screened for carriage of S . pneumoniae with decreased susceptibility to penicillin . Nasopharyngeal samples were obtained from children visiting child health centres for routine health control . RESULTS: Streptococus pneumoniae was found in 322 samples and 18 strains (5.6%, CI95 3.4; 8.8) of all pneumococci showed decreased susceptibility to penicillin G with minimum inhibitory concentrations (MICs) ranging from 0.125 to 1.0 mg/l . The proportion of strains with decreased susceptibility was similar to that found in a laboratory-based material (6%), from the same geographical area and time period . A majority of the children with strains with decreased susceptibility to penicillin (n = 11) were not attending day-care centres . CONCLUSIONS: The prevalence of S . pneumoniae with reduced susceptibility to penicillin is still low in unselected healthy Swedish children.

Am J Infect Control, 2000 Jun, 28(3), 239 - 43
Streptococcus pneumoniae: bacteremia in an era of penicillin resistance; Castillo EM et al.; BACKGROUND: The proportion of penicillin-resistant Streptococcus pneumoniae isolates and associated risk factors varies by geographic area in the United States . We conducted a retrospective study to determine the extent of penicillin-nonsusceptible S pneumoniae bacteremia and associated risk factors in a tertiary care medical center in San Diego . METHODS: Patients with S pneumoniae bacteremia at the University of California, San Diego Medical Center from September 15, 1991, through July 31, 1998, were identified by hospital-based computerized microbiology records . Hospital records included demographic information, patient data, and antibiotic prescription records for patients with bacteremia as a result of S pneumoniae . Univariate and multivariate analyses were used to determine risk factors for penicillin-nonsusceptible S pneumoniae bacteremia . RESULTS: Of 281 isolates of S pneumoniae identified, 192 (68%) were from hospitalized patients . After controlling for other factors, patients from 1 to 5 years of age (P = .01; odds ratio {OR} = 3.96; 95% CI, 1.50 to 10.44), 6 to 18 years of age (P =.04; OR = 6.42; 95% CI, 1.13 to 36.51), and HIV seropositive patients (P =.002; OR = 5.12; 95% CI, 1.83 to 14.32) were more likely to have penicillin-nonsusceptible S pneumoniae bacteremia . There was a significant increasing trend of penicillin-nonsusceptible S pneumoniae bacteremia from 14% in 1991 to 42% in 1998 (P = .001; OR = 1.42; 95% CI, 1.16 to 1.73); this included only 2 isolates that were highly resistant to penicillin . There was no increase in mortality in patients who had penicillin-nonsusceptible S pneumoniae bacteremia . CONCLUSION: With the increase in S pneumoniae resistance to penicillin, it is important to continue surveillance of infections caused by S pneumoniae . Hospital-based studies are useful for tracking epidemiologically important pathogens.

Prim, Care Update Ob Gyns . 1998 Jul 1, 5(4), 148 - 149
Strategies to decrease costs associated with GBS prophylaxis in preterm gestations; Nguyen T et al.; Objective: 1) To evaluate the costs associated with a practice of routinely culturing women for Group B beta-Streptococcus (GBS) who are at risk for preterm delivery . 2) To evaluate the charges associated with a policy of empiric antibiotic therapy in women suspected of imminent delivery prior to 37 weeks gestation.Methods: In our hospital, women who present with preterm contractions (PTC), preterm labor (defined as uterine contractions resulting in cervical change, PTL), and preterm rupture of the membranes (PROM) were cultured for GBS . Women with PTL and PROM received parenteral antibiotic therapy pending availability of culture results (48 hours) . We reviewed the records of women who participated in a study to determine the sensitivity and specificity of a rapid test for GBS (Am J Obstet Gynecol 1997;176:S35) . Results of the Lim broth culture, our gold standard, were used for this analysis . The charges for performing cultures ($32/culture) and administering intravenous ampicillin ($54/dose) were calculated.Results: There were 118 women with PTC, 52 women with PTL, and 64 with PROM . Thirty-four (14.5%) of the cultures were positive . The results are presented below.In women with PTC, the incidence of GBS was 12.7% . The culture results were available and guided care in only the 6 women who delivered between 2 and 7 days . In women with PTL the incidence of positive cultures was 11.5% . All of the women received antibiotics pending results of cultures . The majority of the women had delivery delayed 48 hours until results were available . Care was modified in the 7 women who delivered between 2 and 7 days . In women with PROM the incidence of GBS was 20.3% . The culture results were available and guided therapy in 11 women.Conclusions: Our findings suggest that GBS cultures have limited clinical value in women with PTC . Only 6 women, 5.5%, had their care modified as a result of the cultures, at a cost of $3776 . In women with PTL, we over-treated the majority of women with antibiotics, most of whom delivered after culture results were available . Cultures had minimal impact on management . Antibiotics should be reserved for women whose labor is progressing on tocolysis . In women with PROM, most delivered prior to availability of culture results . We would have saved $2048 had no cultures been obtained . These results are probably irrelevant, if routine antibiotic administration is utilized in PROM to prolong latency intervals regardless of GBS status.

Br J Ophthalmol, 2000 Jun, 84(6), 614 - 7
Management of orbital lymphangioma using intralesional injection of OK-432; Suzuki Y et al.; AIM: To treat orbital lymphangioma with an intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin) . METHOD: A 14 year old boy had a right orbital cystic lymphangioma . The visual acuity in the eye was 20/28 . In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen . The second treatment was performed with 0.04 mg of OK-432 . RESULT: 4 months later, the lesion had totally shrunk to fibrous tissue . The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents . Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared . No recurrence was noted 1 year after treatment . CONCLUSION: An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin . OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.

J Infect Dis, 2000 Jun, 181(6), 2095 - 8 Epub 2000 May 26.
Rifampin reduces production of reactive oxygen species of cerebrospinal fluid phagocytes and hippocampal neuronal apoptosis in experimental Streptococcus pneumoniae meningitis; Bottcher T et al.; Bacterial compounds induce the production of reactive oxygen species (ROS) in meningitis . Rifampin releases smaller quantities of proinflammatory compounds from Streptococcus pneumoniae than do beta-lactam antibiotics . Therefore, rabbits infected intracisternally with S . pneumoniae were treated intravenously either with rifampin 5 mg/kg/h or ceftriaxone 10 mg/kg/h (n=9 each) . Before initiation of antibiotic treatment, a strong positive correlation between ROS production of cerebrospinal fluid (CSF) phagocyte populations and bacterial CSF titers was observed (granulocytes: rs=.90, P<.0001; monocytes: rs=.81, P<.0001) . CSF leukocytes from rifampin-treated rabbits produced less ROS (monocytes at 2 h after initiation of treatment: P=.045; at 5 h: P=.014; granulocytes at 5 h: P=.036) than did leukocytes from animals receiving ceftriaxone . The CSF malondialdehyde concentrations and the density of apoptotic neurons in the dentate gyrus were lower in rifampin- than in ceftriaxone-treated animals (P=.002 and.005) . The use of rifampin to reduce the release of ROS and to decrease secondary brain injury appears promising.

J Infect Dis, 2000 Jun, 181(6), 1983 - 8 Epub 2000 May 22.
Sequential colonization by Streptococcus pneumoniae of healthy children living in an orphanage; Raymond J et al.; A prospective study of nasopharyngeal colonization by Streptococcus pneumoniae in the exceptional conditions of a closed community of abandoned children was done over a 1-year period; 71 children (age <24 months) were studied monthly . S . pneumoniae was isolated from 58 (81.7%), and 94.5% of the 111 isolates were resistant to penicillin . The mean rate of carriage was estimated at 57.4%, ranging from 42.8% to 70.4% . Children were sequentially colonized by a mean of 3 different isolates . The mean duration of carriage for a given isolate was approximately 2.2 months . Serotyping and molecular typing by pulsed-field gel electrophoresis showed that children were colonized by a limited number of clones belonging to only 4 serotypes and 4 pulsotypes . These clones rapidly spread in the community and colonized the children in waves, with a rapid turnover of S . pneumoniae isolates, facilitated by close contact between children.

J Infect Dis, 2000 Jun, 181(6), 1979 - 82 Epub 2000 May 31.
Low cord blood type 14 pneumococcal IgG1 but not IgG2 antibody predicts early infant otitis media; Lockhart NJ et al.; Type-specific IgG1 and IgG2 antibodies to Streptococcus pneumoniae capsular polysaccharides 14 and 19F were measured in cord blood samples from 425 neonates, to determine which antibody subclass was most strongly associated with otitis media (OM) during the first 6 months of life (early OM) . Early OM was significantly associated with type 14 IgG1 antibody in the lowest antibody quartile (P=.055) but not with type 19F IgG1 antibody or with either IgG2 antibody . IgG1 and IgG2 antibodies were significantly intercorrelated for type 14 (r=.52, P<.001) and type 19F (r=.38, P<.001) . Multivariate analysis revealed that having type 14 IgG1 antibody in the lowest quartile, child care attendance, and sibling and maternal OM history were independent risk factors for early OM . Although type-specific pneumococcal IgG2 antibody concentrations were significantly higher than IgG1 concentrations, IgG2 antibodies apparently are not protective against OM during early infancy.

J Infect Dis, 2000 Jun, 181(6), 1971 - 8 Epub 2000 May 31.
Molecular epidemiology survey of penicillin-susceptible and -resistant Streptococcus pneumoniae recovered from patients with meningitis in France; Doit C et al.; The genetic diversity of Streptococcus pneumoniae isolates (n=291) recovered from cerebrospinal fluid of patients with meningitis in France was investigated by restriction fragment length polymorphism analysis of the ribosomal RNA gene regions and of the pbp2b and 2x genes . Statistical analysis of the data by factorial analysis of correspondence established the following: penicillin-susceptible isolates had a high level of genetic diversity, especially those belonging to serogroups frequently associated with carriage; capsular serotype switches could occur among penicillin-susceptible and -resistant isolates; and the mechanisms of acquired penicillin resistance were clearly distinct in isolates with penicillin minimum inhibitory concentration (MIC) values <1 mg/L and isolates with penicillin MIC values >/=1 mg/L . Thus, an increase in the penicillin MIC for a given strain, from intermediate to high-level resistance would be a rare event.

J Fam Pract, 2000 May, 49(5), 447 - 8
The necessity of both anorectal and vaginal cultures for group B streptococcus screening during pregnancy; Quinlan JD et al.; BACKGROUND: Group B streptococcus (GBS) sepsis affects approximately 2 of every 1000 newborns . In an effort to decrease the incidence of neonatal GBS infection, the Centers for Disease Control and Prevention have established guidelines for screening and treatment during pregnancy . One strategy includes obtaining both vaginal and anorectal GBS cultures, then treating patients whose cultures are positive . Many of our patients are reluctant to undergo anorectal cultures . We conducted a study to determine whether performing cultures of both the vagina and anorectum would change patient management . METHODS: We obtained vaginal and anorectal GBS cultures from 222 consecutive patients at 35 to 37 weeks' gestation . RESULTS: Fifty-four patients (24.3%) had positive GBS cultures . Of those women, 10 (18.5%) had negative vaginal but positive rectal cultures . Thus, nearly one fifth of the patients with GBS colonization would not have received intrapartum antibiotics if only vaginal cultures had been performed . CONCLUSIONS: Health care providers caring for pregnant patients should consider obtaining both vaginal and anorectal cultures when screening for Group B streptococcus.

Eur Respir J, 1999 Jan, 13(1), 175 - 9
Search for agents causing atypical pneumonia in HIV-positive patients by inhibitor-controlled PCR assays; Tarp B et al.; Pneumonia is one of the most frequent complications in acquired immunodeficiency syndrome-patients with Pneumocystis carinii as the leading cause . The true prevalence of atypical agents such as Chlamydia pneumoniae, C . trachomatis, Legionella pneumophila and Mycoplasma pneumoniae in this population of patients is unknown as the currently used method for diagnosing these agents is measurement of antibody levels . However, this method is of limited value in human immunodeficiency virus (HIV)-positive patients who may have a compromised antibody response . To evaluate the prevalence of Chlamydia spp., Legionella spp . and M . pneumoniae in HIV-infected patients with pulmonary disease, this retrospective study has applied inhibitor-controlled polymerase chain reaction analyses on 103 bronchoalveolar lavage (BAL) fluids representing 103 episodes of pneumonia in 83 HIV-positive patients . L . pneumophila was detected in 1% of the BAL fluids and M . pneumoniae was found as a coexisting pathogen in 2% of the samples . Chlamydia spp . could not be detected in any of the BAL fluids . By culture and staining methods 106 other microorganisms were detected with P . carinii and Streptococcus pneumoniae as the most frequently occurring . Pneumonia due to Chlamydia pneumoniae, Legionella pneumophila or Mycoplasma pneumoniae seems to be rare in Danish human immunodeficiency virus-infected patients, but might be considered as a possible cause in cases of treatment failure.

Nippon Ganka Gakkai Zasshi, 2000 May, 104(5), 328 - 33
{Molecular biological analysis of retinal and streptococcal heat-shock protein 60}; Tanaka T et al.; PURPOSE: The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behcet's disease suggests a role of oral Streptococcus in the etiology of this disease . Heat-treated Streptococcus antigen can induce ocular inflammation or systemic symptoms in Behcet's disease patients . Furthermore, the presence of an autoantibody against retinal heat-shock protein 60 (HSP 60) has been detected in the sera of these patients . Injection of extracted retinal HSP 60 also induces experimental uveitis in treated rats . The characteristics of retinal HSP 60 and HSP 60 from S . pyogenes were evaluated using a molecular biological approach . METHODS: The gene encoding HSP 60 was isolated by polymerase chain reaction (PCR) from a bovine retinal cDNA library and from S . pyogenes DNA . The DNA sequence of the HSP 60 coding region was determined, and the amino acid sequences of the encoded proteins were predicted from the DNA sequence . The synthetic peptide (50 nmol) was emulsified with Freund's complete adjuvant and injected into rats . RESULTS: Comparison of the amino acid sequences of Streptococcal and bovine retinal HSP 60 revealed about 200 residue regions with 47% homology . Experimental uveitis was mainly induced in rats inoculated with retinal HSP 60-derived peptide or Streptococcus HSP 60-derived peptide that is equivalent to residues 245-259 of human HSP 65 . DISCUSSION: The retinal and Streptococcal HSP 60 amino acid composition is thought to be important and useful for investigating the mechanisms involved in the induction of Behcet's disease.

Rev Med Chil, 1999 Dec, 127(12), 1462 - 8
{Dental fluorosis: quantification of Streptococcus mutans in school children from Mamiña, Chile . A longitudinal study}; Linossier A et al.; BACKGROUND: High fluorine concentrations in drinking water are associated with a decrease in the amount of salivary S mutants . Taking into account that clinical dental fluorosis can appear with 1.5 ppm of fluorine in the drinking water, fluorine concentrations in Mamina is 2.4 ppm . AIM: To quantify salivary S mutans in school age children from Mamina, a zone with a high fluorine content in the drinking water, during one year . MATERIAL AND METHODS: During 1997 and 1998, dental health was assessed and salivary samples were obtained from 51 children (27 male) aged 10 +/- 2 years to quantify S mutans . RESULTS: Most children studied had more than 10(5) salivary S mutans colony forming units . No changes in the rates of infection or dental health characteristics were observed during the observation year . CONCLUSIONS: High fluorine content in the drinking water did not have an effect on salivary S mutans infection in this population.

Rev Med Chil, 1999 Dec, 127(12), 1447 - 52
{Emergence of resistance to macrolides in Streptococcus pyogenes}; Vinagre C et al.; BACKGROUND: Diseases produced by Streptoccocus pyogenes are still a problem in Chile, as in the rest of the world . It exhibits in vitro susceptibility to different antimicrobials, but penicillin continues to be the treatment of choice . Alternative drugs have been developed for allergic patients, such as erythromycin, new macrolides and cephalosporins . Nevertheless, resistant strains are appearing due to the indiscriminate use of macrolides . AIM: To assess present antimicrobial susceptibility of S Pyogenes strains isolated from chilean patients . MATERIAL AND METHODS: The susceptibility to penicillin, macrolides, clindamycin, cephalotin and vancomycin of 153 S Pyogenes strains, obtained from different health centers of the Metropolitan Region and isolated between 1996 and 1998, was assessed using the Kirby-Bauer method . Agar dilution minimal inhibitory concentration was then determined to macrolide resistant strains . RESULTS: All strains were susceptible to penicillin . There was a 7.2% cross-resistance to macrolides . CONCLUSIONS: These results confirm that S Pyogenes resistance to macrolides has increased considerably in the Metropolitan Region of Chile during the last years.

J Clin Microbiol, 2000 Jun, 38(6), 2450 - 2
Recurrent bacteremic peritonitis caused by Enterococcus cecorum in a patient with liver cirrhosis; Hsueh PR et al.; Enterococcus cecorum (formerly Streptococcus cecorum), originally isolated from poultry intestines, has rarely been encountered in human diseases . A 60-year-old man with liver cirrhosis and hepatocellular carcinoma developed peritonitis on the seventh day of his hospitalization . Cultures of one blood sample and one ascites fluid sample obtained on that day both grew E . cecorum . The patient received intravenous cefoxitin therapy and initially responded well . Unfortunately, another episode of peritonitis associated with septic shock developed 24 days after the start of treatment, and culture of one blood specimen yielded the same organism . The isolates were identified by the conventional biochemical tests, the API Rapid ID 32 Strep system, and the API ZYM system (both systems from bioMerieux, Marcy L'Etoile, France) and were further confirmed by cellular fatty acid chromatography and 16S rRNA gene partial sequencing . The identical biotype, antibiotype, and random amplified polymorphic DNA pattern of the three isolates documented the long-term persistence of this organism in the patient . To the best of our knowledge, this is the first clinical description of recurrent bacteremic peritonitis caused by E . cecorum.

J Clin Microbiol, 2000 Jun, 38(6), 2141 - 9
Macrorestriction fingerprinting of "Streptococcus milleri" group bacteria by pulsed-field gel electrophoresis; Bartie KL et al.; Although isolates of the "Streptococcus milleri" group (SMG) of bacteria are regarded as members of the commensal microflora of the body, they are frequently encountered in purulent infections from a range of body sites . The genetic diversity of 91 epidemiologically unrelated SMG isolates (including 37 commensal strains and 49 disease-associated strains) was analyzed by macrorestriction fingerprinting (MF) . The genomes were digested with SmaI and ApaI independently, and fragments were resolved by pulsed-field gel electrophoresis . Similarities between banding profiles were determined, and strains were clustered on this basis into dendrograms . In common with other commensal species that have been examined by MF, considerable genetic diversity was revealed . In addition, the clustering of strains tended to support the current taxonomic position of this heterogeneous group . The present study has shown that MF is a powerful tool for characterization of SMG strains and that its use is likely to be of great value in epidemiological and population genetic studies of this group of bacteria.

J Clin Microbiol, 2000 Jun, 38(6), 2103 - 7
High rate of tetracycline resistance in Streptococcus pyogenes in Iran: an epidemiological study; Jasir A et al.; Streptococcus pyogenes, a major human pathogen, is still considered susceptible to beta-lactams, but for other relevant antibiotics, highly variable resistance rates have been reported . Since no data were available from Iran, we tested 1,335 throat isolates from two different regions of the country for their antibiotic susceptibilities and, for comparison, a collection of 80 strains isolated from 1989 to 1991 . Erythromycin resistance was uncommon (0.6%), whereas an overall high rate of tetracycline resistance was found, increasing between 1989-1991 and 1995-1997 from 23 to 42% . The tetracycline-resistant strains belonged to more than 10 different T types, the majority being types 4, 11, and B3264 . By conventional M typing of 406 tetracycline-resistant isolates, more than 20 different M types were found . Approximately 50% of the strains were nontypeable by T agglutination as well as serological M typing; however, by genotyping by a combined PCR-capture-enzyme-linked immunosorbent assay, many of these strains were successfully emm typed . We conclude that the high rate of tetracycline resistance among Iranian S . pyogenes isolates is due to multiclonal dissemination of resistance within the streptococcal population rather than epidemic spread of single clones.

Eur J Clin Microbiol Infect Dis, 2000 Apr, 19(4), 288 - 93
Carriage of antibiotic-resistant Streptococcus pneumoniae in Greek infants and toddlers; Syrogiannopoulos GA et al.; The prevalence, resistance patterns and serotypes of antibiotic-resistant Streptococcus pneumoniae strains recovered from Greek carriers under 24 months of age were studied . From February 1997 to April 1998, nasopharyngeal cultures were performed in 1,269 children (ages 2-23 months, median 11 months) living in various areas of central and southern Greece . Resistance (including both intermediate and resistant isolates) to one or more antimicrobial agents was found in 132 of the 421 (31%) Streptococcus pneumoniae isolates, as follows: penicillin, 9% intermediate, 7.6% resistant; cefotaxime, 5.2% intermediate, 0.5% resistant; erythromycin, 0.7% intermediate, 18.1% resistant; clindamycin, 0.2% intermediate, 12.4% resistant; tetracycline, 0.7% intermediate, 16.4% resistant; chloramphenicol, 12.4% resistant; and trimethoprim-sulfamethoxazole, 3.8% intermediate, 14.3% resistant . The MICs of penicillin for 66% of the penicillin-nonsusceptible pneumococci were 1-4 microg/ml . Multidrug resistance was found in 64% of penicillin-nonsusceptible and 37% of penicillin-susceptible strains . Sixty-two percent of the penicillin-susceptible, multidrug-resistant strains belonged to serotype 6B and were resistant to all five non-beta-lactam agents tested . This notable serotype 6B resistance pattern was described for the first time in a previous study performed from December 1995 to February 1996 in the city of Patras, southwestern Greece . Seventy-two percent of antibiotic-resistant isolates belonged to serotypes 6B, 9V, 14, 18C, 19F and 23F . These results document the spread of resistant pneumococcal strains in central and southern Greece, many of which are multidrug resistant.

Protein Expr Purif, 2000 Jun, 19(1), 158 - 72
Expression of active monomeric and dimeric nuclease A from the gram-positive Streptococcus gordonii surface protein expression system; Dutton EK et al.; We used the surface protein expression (SPEX) system to express an anchored and a secreted form of staphylococcal nuclease A (NucA) from gram-positive bacteria . NucA is a small ( approximately 18 kDa), extracellular, monomeric enzyme from Staphylococcus aureus . A deletion of amino acids 114-119 causes monomeric NucA to form homodimers . The DNA sequence encoding either wild-type or deletion mutant NucA was cloned via homologous recombination into Streptococcus gordonii . S . gordonii strains expressing either anchored or secreted, monomeric or dimeric NucA were isolated and tested for enzymatic activity using a novel fluorescence enzyme assay . We show that active monomeric and dimeric NucA enzyme can be expressed either anchored on the cell surface or secreted into the culture medium . The activity of the dimer NucA was approximately 100-fold less than the monomer . Secreted and anchored, monomeric NucA migrated on SDS-polyacrylamide gels at approximately 18 or approximately 30 kDa, respectively . In addition, similar to S . aureus NucA, the S . gordonii recombinant NucA enzyme was dependent on CaCl(2) and was heat stable . In contrast, however, the recombinant NucA activity was maximal at pH 7.0-7.5 whereas S . aureus NucA was maximal at pH 9.0 . These results show, for the first time, expression of active enzyme and polymeric protein in secreted and anchored forms using SPEX . This further demonstrates the utility of this gram-positive surface protein expression system as a potential commensal bacterial delivery system for active, therapeutic enzymes, biopharmaceuticals, or vaccines .

Lancet, 2000 May 20, 355(9217), 1776 - 80
Epidemic nephritis in Nova Serrana, Brazil; Balter S et al.; BACKGROUND: Outbreaks of nephritis have been rare since the 1970s . From December, 1997, to July, 1998, 253 cases of acute nephritis were identified in Nova Serrana, Brazil . Seven patients required dialysis, and three patients died . We did a case-control study to investigate the cause of the outbreak . METHODS: Using a matched cluster design, we examined seven recent patients, their family members (n=23), and members of neighbourhood-matched control households (n=22) . We subsequently interviewed 50 patients and 50 matched controls about exposure to various dairy products . We also cultured dairy foods and took udder-swab and milk samples from cows . FINDINGS: Throat cultures indicated that nephritis was associated with group C Streptococcus equi subspecies zooepidemicus, a cause of bovine mastitis . S . zooepidemicus was detected in four of seven case households (six of 30 people) and no control households (p=0.09) . Patients were more likely than matched controls to have consumed a locally produced cheese called queijo fresco (matched odds ratio 2.1, p=0.05) . The nephritis attack rate was 4.5 per 1000 in Nova Serrana but 18 per 1000 in the village Quilombo do Gaia (p=0.003) . The largest supplier of unpasteurized queijo fresco was a farm in Quilombo do Gaia . S . zooepidemicus was not detected in food samples or in swabs collected from cows in August, 1998, although mastitis was evident among cows on the suspected farm . Throat cultures of the two women who prepared cheese on this farm yielded the outbreak strain of S . zooepidemicus . After the cheese was removed from the distribution system, no further cases were reported . INTERPRETATION: A large outbreak of glomerulonephritis was attributed to S . zooepidemicus in unpasteurised cheese . This outbreak highlights the dangers of consuming unpasteurized dairy products and need for global efforts to promote food safety.

Cornea, 2000 May, 19(3), 297 - 300
A devastating ocular pathogen: beta-streptococcus Group G; Ritterband DC et al.; PURPOSE: To report the clinical findings, treatment, and outcomes of four cases of beta-streptococcus Group G (BHS-G) ocular infection . METHODS: The medical and microbiologic records of four cases of BHS-G ocular infection were retrospectively reviewed . RESULTS: Two cases of BHS-G endophthalmitis and two cases of BHS-G keratitis were recorded . Three patients developed fulminant infection within 12 hours of the onset of symptoms . One patient's history was incomplete . One patient developed endophthalmitis from a contaminated donor button; another following cataract surgery . One developed keratitis in a keratoplasty suture tract; and another patient developed a corneal abscess after being struck with a tree branch . The patient with the contaminated donor button developed overwhelming endophthalmitis resulting in no light perception vision, severe pain, and evisceration . The postoperative cataract patient developed a purulent endophthalmitis and is still hypotonus with light perception vision . The second keratitis patient developed a significant suture abscess with marked stromal loss but eventually healed . The traumatic keratitis patient developed a large ulcer with hypopyon and descemetocele but was lost to follow-up . CONCLUSIONS: This is the first report of a series of BHS-G ocular infections . The ocular infections were characterized by rapid onset, extreme inflammation, and--despite in vitro antibiotic sensitivity--a poor or sluggish response to antibiotic therapy.

Microbiology, 2000 May, 146 ( Pt 5), 1187 - 94
Localization and characterization of the ligand-binding domain of the fibrinogen-binding protein (FgBP) of Streptococcus equi subsp . equi; Meehan M et al.; The group C streptococcus Streptococcus equi subsp . equi possesses a 498-residue major cell-wall-associated protein (FgBP) which binds horse fibrinogen (Fg), reacts with convalescent horse serum and protects against lethal S . equi challenge in a small animal model . In the present study, analysis of a panel of 17 purified N- and C-terminal FgBP truncates by ligand affinity blotting and SDS-PAGE revealed that the region required for maximum binding of Fg extended over the first half of the mature protein . The C-terminal two-thirds of this domain is predicted to be alpha-helical coiled-coil and the N-terminal one-third to possess non-coiled-coil single strands . Residues at the extreme N-terminus and within the coiled-coil region are both required for ligand binding . A high incidence of alpha-helical coiled-coil structure also seems to be responsible in part for the aberrant mobility of FgBP on SDS gels . The efficiency with which FgBP binds Fg from different animal species decreases in the order horse > mouse, pig > rat > sheep, dog, bovine, human . Binding to horse Fg is inversely related to temperature over the range 45-4 degrees C and is independent of Ca2+ ions . MS analysis provided corroborative evidence that FgBP is covalently linked to the cell wall peptidoglycan.

Microbiology, 2000 May, 146 ( Pt 5), 1179 - 85
Inactivation of the ptsI gene encoding enzyme I of the sugar phosphotransferase system of Streptococcus salivarius: effects on growth and urease expression; Weaver CA et al.; The urease genes of Streptococcus salivarius 57.1 are tightly repressed in cells growing at neutral pH . When cells are cultivated at acidic pH values, the urease genes become derepressed and transcription is enhanced when cells are growing under carbohydrate-excess conditions . Previously, the authors proposed that the bacterial sugar:phosphotransferase system (PTS) modulated the DNA-binding activity by phosphorylation of the urease repressor when carbohydrate was limiting . The purpose of this study was to assess whether enzyme I (EI) of the PTS could be involved in modulating urease expression in response to carbohydrate availability . An EI-deficient strain (ptsI18-3) of S . salivarius 57.1 was constructed by insertional inactivation of the ptsI gene . The mutant had no measurable PTS activity and lacked EI, as assessed by Western analysis . The mutant grew as well as the wild-type strain on the non-PTS sugar lactose, and grew better than the parent when another non-PTS sugar, galactose, was the sole carbohydrate . The mutant was able to grow with glucose as the sole carbohydrate, but displayed a 24 h lag time and had a generation time some threefold longer than strain 57.1 . The mean OD600 attained after 48 h by ptsI18-3 supplied with fructose was 0.16, with no additional growth observed even after 3 d . Urease expression in the wild-type and mutant strains was assessed in continuous chemostat culture . Repression of urease at neutral pH was seen in both strains under all conditions tested . Growth of wild-type cells on limiting concentrations of lactose resulted in very low levels of urease expression compared with growth on PTS sugars . In contrast, under similar conditions, urease expression in ptsI18-3 was restored to levels seen in the parent growing on PTS sugars . Growth under conditions of lactose excess resulted in further derepression of urease, but ptsI18-3 expressed about threefold higher urease activity than 57.1 . The results support a role for EI in urease regulation, but also indicate that additional factors may be important in regulating urease gene expression.

Neuropediatrics, 2000 Apr, 31(2), 97 - 9
Cerebellar involvement as a rare complication of pneumococcal meningitis; Drost G et al.; A 4-year old girl with meningitis, caused by streptococcus pneumoniae, developed a subcoma with respiratory insufficiency, followed by a severe cerebellar syndrome . Cerebellar involvement after regaining consciousness consisted of a symmetrical ataxia and mutism . This mutism changed into dysarthria and finally into normal speech . Magnetic resonance imaging revealed lesions in both cerebellar hemispheres, suggesting cerebellitis . She recovered with prompt antibiotic treatment.

Indian J Pediatr, 1996 Jul-Aug, 63(4), 549 - 52
Sino-bronchial syndrome in children with asthma; Rajajee S et al.; Thirty children in the age group of 2 to 12 years were brought with a history of recurrent non-seasonal moderate to severe wheezy episodes associated with symptoms of nasal congestion, sneezing and occasional headache . All of them had maxillary or pan sinusitis with 26 having associated right, left or bilateral lower lobe pneumonitis or bronchiectasis . Serum immunoglobulins were normal in 22 and was not done in eight . There was positive (2 to 4+ above negative control) skin test response to dust and dust mite in 15 of the 22 children tested . Throat swabs/sputum or nasal secretions grew B-hemolytic streptococcus or streptococcus pneumoniae in twenty-seven . All the children were put on bactericidal drugs for 6 to 8 weeks and bronchodilators were used when needed . At the end of 6 to 8 weeks follow-up X-ray of sinuses and chest showed significant clearing of the lesions which coincided with marked clinical improvement . Sinus X-ray should be considered in bronchial asthma resistant to medical management since untreated bacterial sinusitis can be an underlying cause of chronic poorly controlled asthma.

Acta Paediatr, 2000 Apr, 89(4), 431 - 5
Vulvar symptoms in paediatric and adolescent patients; Piippo S et al.; Vulvovaginal symptoms in children and young adolescents are not yet very well understood, nor is the actual incidence known . This study evaluates the character and possible infectious aetiology of vulvar symptoms of females aged up to 16 y . The signs, symptoms and bacteriological findings of 68 consecutive cases were studied . The study was conducted in the University Hospital of Tampere at a special gynaecological consultation clinic for children and adolescents . Sixty-eight patients were included in the study: 48 girls (71%) were prepubertal, at Tanner stage M1P1, 26 patients were 2-4-y-old and 15 were 5-7-y-old . The duration of symptoms was known for 46 patients: 41% had had symptoms for >1 mo and 20% for >6 mo . Forty-eight patients had abnormal clinical findings on examination and 16 (33%) of them had an infectious aetiology . Streptococcus pyogenes infection was identified in 11 (16%) patients, all of whom had symptoms . Candida was identified in 6 (9%) patients . No infectious aetiology was found among 26 patients who had symptoms and abnormal clinical findings . Vulvovaginal symptoms during childhood are more common among younger children (<7 y) . In 67% of patients no infectious aetiology could be found . Samples for microbiological culture should be taken from symptomatic patients and symptomatic areas . Cultures of Candida and bacteria are necessary but usually sufficient . If a microbiological aetiology is established, treatment can be assigned accordingly . Patients with vulvar symptoms and findings but with an unclear aetiology need support and advice on proper hygiene and can intermittently use mild corticosteroids locally.

Acta Paediatr, 2000 Apr, 89(4), 427 - 30
Paediatric infective endocarditis: 19-year experience at a tertiary care hospital in a developing country; Bitar FF et al.; A retrospective study was undertaken to study children who presented with infective endocarditis (IE) to a university teaching hospital in Beirut, Lebanon, between January 1977 and May 1995 . Of 41 patients with IE (24F, 17M), 28 (68%) were diagnosed between 1977 and 1985 . Patients' ages ranged from 3 to 18 y (mean age 11.3+/-2.8 y), and 13 patients were <10 y of age . Clinical presentations included: fever (in 88%), heart failure (in 39%), neurologic findings (in 20%) and embolic phenomena (in 22%) . Nineteen patients (46%) had underlying congenital heart disease (CHD) with tetralogy of Fallot and pulmonary stenosis being the most common . Sixteen patients (39%) had underlying rheumatic heart disease (RHD) . A total of 5 children (12%) with normal cardiac anatomy had IE . One had underlying acquired viral myocarditis with mitral insufficiency . Echocardiography showed vegetations in 60% . Blood cultures were positive in 31 patients (76%) . IE occurred in three patients following cardiac surgery . In one patient it occurred within 2 mo of surgery and in the other two it occurred within 6 mo . Streptococcus viridans and Staphylococcus aureus were the two most commonly isolated bacteria . Overall mortality rate was 29% (not statistically significant between patients presenting between 1977-1985 and 1986-1995; p = 0.17) . There was no statistically significant difference in mortality among the groups (five in the group with CHD, six with RHD and one with structurally normal heart) . This study demonstrates that RHD is an important underlying cause of IE in children in our community . This finding is similar to those in other developing countries and different from those in developed countries . Distribution of pathogens and CHD in our study is comparable to some reports in the literature, except for the higher proportion of patients with underlying pulmonary stenosis . Bacterial endocarditis prophylaxis should be emphasized in patients with RHD or pulmonary stenosis.

Indian J Pediatr, 1996 Mar-Apr, 63(2), 204 - 9
Infective endocarditis in infants and children; Bhat AW et al.; Due to changing characteristics of infective endocarditis in the past two decades, we, retrospectively analysed 28 cases of infective endocarditis in children of age less than 15 years at Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar from December, 1983 to November, 1993 . The incidence of disease was observed as 1.5 cases/1000 children admitted with a M:F ratio of 2:1 . Three patients were of age less than 2 years (group I) as 25 were above 2 years of age (group II) . The two groups had significant difference in portal of entry of infection, infective microorganisms, echocardiography and prognosis . Congenital heart disease was the commonest underlying cardiac lesion in 24 (85.71%) patients . Portal of entry of infection was apparent in 35.71% only; dental route being more frequent in group II . Streptococcus viridans (in 9 cases) followed by staphylococcus aureus (in 4 cases) were the two common organisms isolated . Patients were treated, for a period of 4-6 weeks with a over all mortality rate of 25% . Factors associated with poor prognosis were age < 2 years, staphylococcal infection ad negative blood cultures . Heart failure resistant to medical therapy was a leading cause of death.

Biochemistry, 2000 May 30, 39(21), 6440 - 8
Kinetic and structural characterization of a two-domain streptokinase: dissection of domain functionality; Johnsen LB et al.; The mammalian protease plasminogen can be activated by bacterial activators, the three-domain (alpha, beta, gamma) streptokinases and the one-domain (alpha) staphylokinases . These activators act as plasmin(ogen) cofactors, and the resulting complexes initiate proteolytic activity of host plasminogen which facilitates bacterial colonization of the host organism . We have investigated the kinetic mechanism of the plasminogen activation mediated by a novel two-domain (alpha, beta) streptokinase isolated from Streptococcus uberis (Sk(U)) with specificity toward bovine plasminogen . The interaction between Sk(U) and plasminogen occurred in two steps: (1) rapid association of the proteins and (2) slow transition to the active complex Sk(U)-PgA . The complex Sk(U)-PgA converted plasminogen to plasmin with the following parameters: K(m) < or = 1.5 microM and k(cat) = 0.55 s(-)(1) . The ability of proteolytic fragments of Sk(U) to activate plasminogen was investigated . Only two C-terminal segments (97-261 and 123-261), which both contain the beta-domain (126-261), were shown to be active . They initiated plasminogen activation in complex with plasmin, but not with plasminogen, and thereby exhibited functional similarity to the staphylokinase . The fusion protein His(6)-Sk(U) (i.e., Sk(U) with a small N-terminal tag) acted exclusively in complex with plasmin as well . These observations demonstrate that (1) the N-terminal alpha-domain, including a native N-terminus, was necessary for "virgin" activation of the associated plasminogen in the Sk(U)-PgA complex and (2) the C-terminal beta-domain of Sk(U) is important for recognition of the substrate in the Sk(U)-PgA complex.

Curr Microbiol, 2000 Jun, 40(6), 380 - 6
Effects of ammonia and amino acids on the growth and proteolytic activity of three species of rumen bacteria: Prevotella albensis, Butyrivibrio fibrisolvens, and Streptococcus bovis; Sales M et al.; The addition of increasing physiological concentrations of ammonia or amino acids had distinct effects on the growth and proteolytic activity of Streptococcus bovis JB1, Prevotella albensis, and Butyrivibrio fibrisolvens DSM3071 . The growth of S . bovis and B . fibrisolvens was enhanced by NH(3) and AA, and that of P . albensis was reduced compared with a control with protein as the sole source of nitrogen . The proteolytic activity of S . bovis and P . albensis was reduced, but that of B . fibrisolvens was improved . NH(3) seemed to act mainly on the cell-associated fraction of the proteolytic activity, while the action of AA was not specific . In the rumen the proteolytic activity of S . bovis and P . albensis would be optimal at low concentrations of NH(3) or AA (<0.05 and <0.27 g/L respectively) . In contrast, B . fibrisolvens would need higher concentrations (0.5 g/L of NH(3) or 2.7 g/L of AA) . It can be assumed that these bacteria will grow in different ecological niches.

Emerg Infect Dis, 2000 May-Jun, 6(3), 283 - 9
High prevalence of penicillin-nonsusceptible Streptococcus pneumoniae at a community hospital in Oklahoma; Moolenaar RL et al.; During 1997, Oklahoma City's Hospital A reported penicillin-nonsusceptible Streptococcus pneumoniae in almost 67% of isolates . To confirm this finding, all Hospital A S . pneumoniae isolates from October 23, 1997, through February 19, 1998, were tested for antibiotic susceptibility and repeat-tested at two other hospital laboratories . Medical records of Hospital A patients with invasive S . pneumoniae infections during 1994 through 1997 were also reviewed . These data were compared with 1998 statewide sentinel hospital surveillance data for invasive S . pneumoniae . Of 48 S . pneumoniae isolates from Hospital A during October 23, 1997, through February 19, 1998, 31 (65%) were penicillin-nonsusceptible S . pneumoniae, and 23 (48%) were highly penicillin resistant . Similar prevalences were confirmed at the other hospital laboratories; however, significant interlaboratory differences were noted in the determination of third-generation cephalosporin susceptibility . During 1994 through 1997, a trend toward increasing penicillin nonsusceptibility (p <0.05) was noted among S . pneumoniae isolates from nursing home patients . During 1998, 85 (30%) of 282 invasive isolates reported to the state surveillance system were penicillin-nonsusceptible S . pneumoniae; 33 (12%) were highly resistant . The increase in resistance observed is notable; the interlaboratory discrepancies are unexplained . To respond, a vaccination program was implemented at Hospital A, and vaccination efforts were initiated at nursing homes.

Scand J Infect Dis, 2000, 32(2), 133 - 6
Clinical syndromes associated with adult pneumococcal cellulitis; Parada JP et al.; Streptococcus pneumoniae is an uncommonly recognized etiology of cellulitis in adults . A review of the literature uncovered 30 cases of pneumococcal skin infection in adults . Typically, all patients with pneumococcal cellulitis had an underlying chronic illness, or were immunocompromised by drug or alcohol abuse . Pneumococcal cellulitis presents as two distinctive clinical syndromes: one with extremity involvement in individuals with diabetes and substance abuse; and a second involving the head, neck and upper torso in individuals with systemic lupus erythematosis, nephrotic syndrome and hematologic disorders . For each there are statistically significant associations between the location of pneumococcal cellulitis and underlying clinical disorders . In contrast to other common bacterial etiologies, pneumococcal cellulitis is frequently associated with blood stream invasion, tissue necrosis and suppurative complications . Patients often require surgical interventions and prolonged hospitalizations . A high degree of suspicion and early aggressive management is needed for those presenting with cellulitis characterized by bullae and violaceous color.

Int J Syst Evol Microbiol, 2000 Jan, 50 Pt 1, 247 - 9
DNA-DNA reassociation studies of Streptococcus constellatus with unusual 16S rRNA sequences; Jacobs JA et al.; DNA-DNA reassociation studies were performed on previously described 'CI strains', which form an unusual 16S rRNA population within the 'anginosus' group of Streptococcus . The CI strains displayed reassociation values of >70% with the Streptococcus constellatus NCDO 2226T strain, with Tm values <1 degrees C, indicating phylogenetic species identity.

J Cereb Blood Flow Metab, 2000 May, 20(5), 834 - 8
Induced hypothermia in experimental pneumococcal meningitis; Angstwurm K et al.; Pneumococcal meningitis resulting from Streptococcus pneumoniae has a death rate of 28% in adults . In severe head injury and stroke, inflammatory changes and intracranial hypertension are improved by induced hypothermia, which also is neuroprotective . We hypothesized that moderate hypothermia ameliorates inflammatory changes in experimental pneumococcal meningitis . Wistar rats were cooled systemically, and meningitis was induced by pneumococcal cell wall components . The increase of regional cerebral blood flow in the meningitis animals was blocked by hypothermia at 6 hours . The reduction of intracranial pressure correlated with temperature . The influx of leukocytes into the cerebrospinal fluid and levels of tumor necrosis factor alpha in the cerebrospinal fluid were decreased . Cooling the animals 2 hours after meningitis induction to 30.5 degrees C was also protective . We conclude that hypothermia is a new adjuvant approach to reduce meningitis-induced changes, in particular intracranial pressure, in the early phase of the disease.

Arch Intern Med, 2000 May 22, 160(10), 1399 - 408
Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group; Heffelfinger JD et al.; OBJECTIVE: To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP) . METHODS: We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era? (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era? and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP . Published and unpublished data were summarized from the scientific literature and experience of participants . After group presentations and review of background materials, subgroup chairs prepared draft responses, which were discussed as a group . CONCLUSIONS: When implicated in cases of pneumonia, S pneumoniae should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 microg/mL, of intermediate susceptibility if MIC is 2 microg/ mL, and resistant if MIC is no less than 4 microg/mL . For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide (eg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium) . Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide . New fluoroquinolones with improved activity against S pneumoniae can also be used to treat adults with community-acquired pneumonia . To limit the emergence of fluoroquinolone-resistant strains, the new fluoroquinolones should be limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC > or =4 microg/mL) . Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP.

Cutis, 2000 May, 65(5), 318 - 20
Transverse leukonychia with systemic infection; Mautner GH et al.; Transverse white nail bands (leukonychia) have been described in association with systemic illnesses and exposure to toxins, and medications . We describe the occurrence of transverse nail bands in two patients following acute systemic illnesses . In the first case, transverse white nail bands developed in a 30-year-old human immunodeficiency virus-positive man following acute pulmonary tuberculosis . In the second case, transverse white nail bands were noted in an 80-year-old patient following Streptococcus intermedius empyema.

Clin Infect Dis, 1999 Apr, 28(4), 873 - 81
Streptococcus pneumoniae spinal infection in Nottingham, United Kingdom: not a rare event; Turner DP et al.; Pneumonia and meningitis are the most frequent manifestations of Streptococcus pneumoniae infection . Spinal infection is considered to be a rarity . Between 1985 and 1997, 8 patients with spinal infection (vertebral osteomyelitis, 3; spinal epidural abscess, 1; both, 4) due to S . pneumoniae were seen at University Hospital (Nottingham, U.K.) . Predisposing factors for pneumococcal infection were documented for five patients and included diabetes mellitus, alcoholism, and corticosteroid therapy . One patient presented with concomitant meningitis and endocarditis . Clinical features of note were prolonged symptoms and a lack of febrile response . S . pneumoniae was isolated from the blood of five patients . Magnetic resonance imaging was used to localize the spinal infection in five patients . Two cases were managed medically . Three patients died after a protracted illness . A literature search revealed 20 other cases of spinal infections due to S . pneumoniae . The salient features of the cases are summarized.

Clin Infect Dis, 1999 Apr, 28(4), 730 - 5
Pneumococcal drug resistance: the new "special enemy of old age"; Butler JC et al.; Streptococcus pneumoniae is a leading cause of illness and death among the elderly . The recent emergence of drug-resistant strains has complicated selection of antimicrobial therapy for suspected pneumococcal infections . In some areas of North America, nearly 40% of pneumococcal isolates from the blood or cerebrospinal fluid of persons > or = 65 years old had reduced susceptibility to penicillin . Of all penicillin-resistant infections, >30% occur in persons > or = 65 years old . The increasing prevalence of drug-resistant pneumococci and recent outbreaks of pneumococcal disease in chronic-care facilities emphasize the importance of efforts to prevent these infections in the elderly . Limiting selection for drug-resistant strains through judicious use of antimicrobial drugs and preventing invasive pneumococcal infections through increased use of pneumococcal vaccine form the foundation of these efforts.

J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 107 - 10
Bactericidal activity of gemifloxacin and other quinolones against Streptococcus pneumoniae; Morrissey I et al.; This study compared the bactericidal activity of gemifloxacin (SB-265805) and a panel of test quinolones against two ciprofloxacin-resistant pneumococcal strains (Streptococcus pneumoniae 502226 and 503244) and one ciprofloxacin-sensitive strain (S . pneumoniae C3LN4) . Activities were compared by calculating the bactericidal index of these agents . Gemifloxacin was found to be the most bactericidal quinolone tested against these strains . This finding confirms previous data indicating the superior in vitro activity of gemifloxacin against pneumococci, including ciprofloxacin-resistant strains . Although both ciprofloxacin-resistant strains tested had similar quinolone MICs, they differed considerably in their susceptibility to the bactericidal action of these agents . S . pneumoniae 502226 was more readily killed by quinolones than S . pneumoniae 503244 but, as would be expected, both were less susceptible than the ciprofloxacin-sensitive strain . Of the quinolones tested, trovafloxacin showed disproportionally poor activity against the ciprofloxacin-resistant strains even though potent activity was present against the ciprofloxacin-sensitive strain . These data highlight the importance of assessing quinolone bactericidal activity in addition to the MIC when evaluating new members of this antimicrobial class.

J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 101 - 6
Purification of pneumococcal type II topoisomerases and inhibition by gemifloxacin and other quinolones; Morrissey I et al.; Topoisomerase IV and DNA gyrase were purified from a ciprofloxacin-sensitive Streptococcus pneumoniae strain and from two clinical isolates of S . pneumoniae with high-level resistance to ciprofloxacin by means of a gene cloning method in Escherichia coli . All the quinolones tested (gemifloxacin, trovafloxacin, levofloxacin, ciprofloxacin and grepafloxacin) were able to inhibit topoisomerase IV at lower concentrations than those required for DNA gyrase, suggesting that topoisomerase IV is the primary target in the three pneumococci, in agreement with recently published enzyme data . Gemifloxacin (SB-265805) was found to be the most active agent against topoisomerase IV but, surprisingly, not against DNA gyrase . These findings indicate that the potent in vitro activity of gemifloxacin against S . pneumoniae, including ciprofloxacin-resistant strains, results from a strong affinity for pneumococcal topoisomerase IV.

J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 95 - 9
Efflux and target mutations as quinolone resistance mechanisms in clinical isolates of Streptococcus pneumoniae; Broskey J et al.; The aim of this study was to characterize quinolone resistance mechanisms in strains of Streptococcus pneumoniae with increased MICs of ofloxacin . These strains were also tested for their susceptibility to a battery of quinolone antimicrobial agents, including gemifloxacin . Of the S . pneumoniae isolates used, 27 were susceptible to ofloxacin, 18 intermediate and 48 resistant (ofloxacin MIC <4, 4 and >4 mg/L, respectively) . In general, the ofloxacin-susceptible strains had no amino acid substitutions in GyrA, GyrB, ParC or ParE . Moderate increases in MIC were associated with substitutions in the quinolone resistance-determining region (QRDR) of ParC, while the highest MICs were found for strains that also had substitutions in the QRDR of GyrA . The most common substitutions were Ser79-->Phe in ParC and Ser81-->Phe in GyrA . Other substitutions were identified within the QRDR of ParC and outside the QRDR of ParC and ParE; these did not appear to affect susceptibility . The effects of antimicrobial efflux pumps were studied by determining MICs of a range of quinolones in the presence and absence of reserpine, an inhibitor of Gram-positive efflux pumps . Our results indicated that high-level resistance, caused entirely by efflux, was seen in a minority of ofloxacin-resistant S . pneumoniae strains . Testing the susceptibility of quinolone-resistant strains to gemifloxacin, ciprofloxacin, norfloxacin, ofloxacin and trovafloxacin revealed that gemifloxacin was least affected by this large variety of resistance mechanisms and was the only quinolone with MICs of < or =0.5 mg/L for all strains in this study . These results suggest that gemifloxacin is highly potent against S . pneumoniae and may also be effective against strains resistant to other quinolones.

J Antimicrob Chemother, 2000 Apr, 45 Suppl 1, 35 - 9
Activity of gemifloxacin and other new quinolones against Chlamydia pneumoniae: a review; Hammerschlag MR; Quinolones are currently used as empirical therapy for treatment of community-acquired lower respiratory infections as they are effective against a broad range of conventional bacterial and 'atypical' pathogens, including Chlamydia pneumoniae . C . pneumoniae is estimated to be associated with 10-20% of community-acquired pneumonia in adults, and has recently been suggested to play a role in several non-respiratory conditions, including atherosclerosis . The newer, third-generation quinolones have enhanced activity against Gram-positive bacteria, including Streptococcus pneumoniae, and prolonged serum half-lives that permit once-daily dosing . Although gemifloxacin (SB-265805) and other new quinolones have good activity against C . pneumoniae in vitro, practically all published treatment studies have relied on serological diagnosis . Consequently, the microbiological efficacy of these agents in human infection has not been assessed . This paper reviews what is known to date of the in vivo microbiological efficacy of the quinolones against C . pneumoniae, and demonstrates the importance of assessing this parameter when evaluating the clinical utility of these agents in C . pneumoniae infection.

J Infect Dis, 2000 May, 181(5), 1842 - 5 Epub 2000 May 15.
Immune response to surface protein A of Streptococcus pneumoniae and to high-molecular-weight outer membrane protein A of Moraxella catarrhalis in children with acute otitis media; Samukawa T et al.; The immune response was evaluated in 11 children with Streptococcus pneumoniae and in 9 children with Moraxella catarrhalis otitis media . The age of the children had a range of 4-32 months . The mean IgG, IgM, and IgA antibody responses to surface protein A (PspA) of S . pneumoniae in sera from children at the acute and convalescent stages were 4864 versus 5831 ng/mL, P<.05, 1075 versus 3752 ng/mL, P<.05, and 67 versus 93 ng/mL, nonsignificant (NS), respectively . The mean IgG, IgM, and IgA antibody responses to the high-molecular-weight outer membrane protein (UspA) of M . catarrhalis in sera from children at acute and convalescent stages were 710 versus 935 mg/mL, NS; 1895 versus 2646 ng/mL, NS; and 121 versus 204 ng/mL, P<.05, respectively . These data show that PspA and UspA are immunogenic in children after otitis media.

Oper Dent, 1999 Sep-Oct, 24(5), 279 - 85
Evaluation of antibacterial activity of three dentin primers using an in vitro tooth model; Ohmori K et al.; This study compared the antibacterial activities of three dentin primers and investigated a newly designed experimental system using a bovine tooth model method for evaluating antibacterial activity by comparing this method with a conventional disk diffusion method . The antibacterial activities of SA primer in Clearfil Liner Bond, LB primer in Clearfil Liner Bond II, and ED primer in Panavia 21 were evaluated using the conventional disk diffusion method . The 50 microliters aliquot of each primer was applied to three sterilized paper disks, then placed onto Tryptic Soy agar plates already inoculated with Streptococcus mutans . After anaerobic incubation for 48 hours, the diffusion of antibacterial components was determined using the inhibition zone produced around the paper disk . The diameter of the inhibition zones was measured and the average calculated . Standardized cavities (diameter 5.0 mm, depth 3.0 mm) were prepared on the labial surfaces of bovine teeth and inoculated with S mutans (10(6) CFU/microliter) following sterilization by 60Co gamma rays (50 KGy) . The teeth were divided into four groups: SA primer, LB primer, ED primer, and a control group . Except for the control teeth, the cavity preparations were treated with the respective dentin primers, and then firmly sealed with a temporary sealing material . The teeth were placed in bottles containing melted Tryptic Soy agar . Five ml of Tryptic Soy broth was then added to the surface of the hardened Tryptic Soy agar . After 1 week's incubation of the teeth in the bottles at 37 degrees C, the number of bacteria remaining in each cavity was counted, except for eight specimens, which were used for SEM observation . The ED primer showed the widest inhibition zone in the disk diffusion test, which was significantly different from the other primers . Using the bovine tooth model, all dentin primers showed antibacterial activity, with significant differences found among the four groups . The results indicated that ED primer had the strongest antibacterial effect among the three primers.

Miss Dent Assoc J, 1999 4th Quarter, 55(4), 38 - 9
The effect of nicotine on growth of Streptococcus mutans; Keene K et al.; There is little information available concerning the effects of nicotine on oral bacteria; and in particular, Streptococcus mutans, an important microbe in the etiology of dental caries . To test the effects of nicotine, Streptococcus mutans were incubated in either 0 or 10(-1)-10(-7) M concentrations of nicotine and then plated onto mitis-salivarius-bacitracin agar . Colonies were counted and treatment groups compared . Both 10(-1) and 10(-2) M nicotine caused total inhibition of bacterial growth, while 10(-3) and 10(-4) M produced significantly more colonies than control . Also, 10(-6) and 10(-7) M nicotine produced a significant reduction in the mean number of colonies . These results suggest a biphasic, dosage-dependent effect of nicotine on the growth of Streptococcus mutans . Since 10(-3) M nicotine has been reported within the saliva of smokeless tobacco users, use of these products could stimulate growth of Streptococcus mutans and possibly place the user at increased risk for dental caries.

Compr Ther, 2000 Summer, 26(2), 73 - 81
Group A streptococcus necrotizing fasciitis; File TM Jr et al.; Necrotizing fasciitis due to Group A streptococcus has been observed with increasing frequency over the past decade . Appropriate management requires rapid recognition of this life-threatening infection and expeditious antimicrobial therapy as well as surgical debridement or excision of tissue.

J Biol Chem, 2000 May 26, 275(21), 15845 - 50
Biochemical structural analysis of the lantibiotic mutacin II; Krull RE et al.; Mutacin II is a post-translationally modified lantibiotic peptide secreted by Streptococcus mutans T8, which inhibits the energy metabolism of sensitive cells . The deduced amino acid sequence of promutacin II is NRWWQGVVPTVSYECRMNSWQHVFTCC, which is capable of forming three thioether bridges . It was not obvious, however, how the three thioether bridges are organized . To examine the bridging, the cyanogen bromide cleavage products of mutacin II and its variants generated by protein engineering, C15A, C26A, and C15A/C26A, were analyzed by mass spectrometry . Analysis of the wild type molecule and the C15A variant excluded several possibilities and also indicated a high fidelity of formation of the thioether bridges . This allowed us to further resolve the structure by analysis (mass spectrometry and tandem mass spectrometry) of the cyanogen bromide cleavage fragments of the C26A and C15A/C26A mutants . Nuclear magnetic resonance analysis established the presence of one and two dehydrobutyrine residues in mutacin II and the C15A variant, respectively, thus yielding the final structure . The results of this investigation showed that the C-terminal part contains three thioether bridges connecting Cys residues 15, 26, and 27 to Ser/Thr residues 10, 12 and 19, respectively, with Thr(25) being modified to dehydrobutyrine.

J Dairy Sci, 2000 May, 83(5), 945 - 51
Generation of complement fragment C5a in milk is variable among cows; Rainard P et al.; The appearance of chemotactic fragments of complement at sites of infection is an important component of innate immunity . The contribution of C5a, the most biologically active complement fragment, to the recruitment of phagocytes in milk is not well defined, in particular the amount of C5a that is released in normal milk before inflammation . The generation of C5a in normal milk upon activation of complement by invading bacteria depends on the amount of available C5 and on the activity of the C3/C5-convertase of the alternative pathway . Concentrations of C5 were measured in one fore and one rear uninfected quarter of 19 Holstein cows . Values were consistent within cows, but widely dispersed among cows (0.19 to 1.94% blood concentration) . C5 concentrations in milk were loosely related to concentrations in blood . By comparison, the range of milk concentrations of C3 (1.4 to 4.4%, mean 2.46 +/- 0.63% of blood concentration) was narrower . Two groups of six cows with high milk concentrations of C5 (cows H5: mean = 1.31%) and six cows with low milk concentrations of C5 (cow L5: mean = 0.21%) were constituted for further analysis of complement activation . There was a positive correlation between concentrations in milk of BSA and C5, but not between concentrations of BSA and C3 . The activities of the C3- and C5-convertases were assessed through the deposition on complement-activating bacteria (Streptococcus agalactiae) of C3 and C5 fragments, respectively . The deposition of C3 was 1.7-fold higher, and the deposition of C5 was 2.75-fold higher in milk from H5 cows than in milk of L5 cows . Higher concentrations of C5 and better functioning of C5-convertase were mirrored by a much higher concentration of C5a in milk from H5 cows (12.30 ng/ml) than in milk of L5 cows (0.76 ng/ml) after activation of complement with zymosan . These results indicate that cows differed widely in their capacity to generate C5a in milk before inflammation, and that milk C5 concentrations were a primary limiting factor for C5a generation . Cows with the lowest milk concentrations of C5 are likely unable to use the complement system for the initial recruitment of leukocytes.

Fam Med, 2000 May, 32(5), 338 - 41
Improving pneumococcal vaccination rates: a three-step approach; Redfield JR et al.; BACKGROUND: Streptococcus pneumoniae is the cause of significant preventable morbidity and mortality each year, especially among the elderly . This study evaluated the effectiveness of a three-step strategy to improve pneumococcal vaccination rates in patients ages 65 and older . METHODS: We obtained a baseline vaccination rate by chart review of a randomized list of patients ages 65 and older . Interventions that included physician education, a system of office prompts, and patient education were instituted for 1 year . We performed a second chart review to determine the success of the intervention . RESULTS: Vaccination rates increased significantly from 56.7% to 75.8% . No significant difference in initial vaccination rates between men and women was found . Although rates improved for both men and women, only the increase in vaccination for men was significant . CONCLUSIONS: This study shows that an easy and inexpensive intervention can substantially impact pneumococcal vaccination rates . Specifically, a three-step approach that combines provider education, office prompts, and patient education has proven effective.

Biochemistry, 2000 May 9, 39(18), 5450 - 7
Novel purification scheme and functions for a C3-binding protein from Streptococcus pneumoniae; Cheng Q et al.; To isolate microbial proteins capable of binding the third component of complement (C3), we coupled the free sulfhydryl group of methylamine-inactivated C3 to a thiolSepharose matrix . This simple technique facilitated the purification of the first C3-binding protein isolated from a bacterium (Streptococcus pneumoniae) . Both metastable (native) and thioester-disrupted C3 were recognized by this protein; binding of C3 was noncovalent, independent of thioester conformation, and preferential for the C3 alpha-chain . Sequencing of amino-terminal and internal peptides from the C3-binding protein disclosed a proline-rich region spanning approximately 20 amino acids and a signal peptide that had not been previously reported . The gene was isolated from a library of genomic DNA from laboratory strain CP1200 by screening with a 1200 bp PCR product amplified from degenerate oligonucleotides encoding the amino terminal sequence and the internal proline-rich sequence . The open reading frame spanned 1692 bp; all peptide sequences were identified in the translated gene product, which also contained at least three choline-binding repeats at the carboxy-terminus . The gene was conserved, and the translated protein was functionally active in pneumococcal clinical isolates of serotypes 1, 3, 4, 14, and 19F . Serum from a patient recovering from acute pneumococcal infection contained IgG antibodies specific for this protein by immunoblot . Wide conservation among clinical isolates, saturable binding of C3, and the ability to stimulate the human immune response have not previously been reported for this choline-binding protein . A similar biochemical approach should enable the identification of other C3-binding proteins in microorganisms able to elude complement-mediated host defense.

Biochemistry, 2000 May 2, 39(17), 5035 - 44
Limited proteolysis as a structural probe of the soluble alpha-glycerophosphate oxidase from Streptococcus sp; Charrier V et al.; As reported previously {Parsonage, D., Luba, J., Mallett, T . C., and Claiborne, A . (1998) J . Biol . Chem . 273, 23812-23822}, the flavoprotein alpha-glycerophosphate oxidases (GlpOs) from a number of enterococcal and streptococcal sources contain a conserved 50-52 residue insert that is completely absent in the homologous alpha-glycerophosphate dehydrogenases . On limited proteolysis with trypsin, the GlpO from Streptococcus sp . (m = 67.6 kDa) is readily converted to two major fragments corresponding to masses of approximately 40 and 23 kDa . The combined application of sequence and mass spectrometric analyses demonstrates that the 40-kDa fragment represents the N-terminus of intact GlpO (Met1-Lys368; 40.5 kDa), while the 23-kDa band represents a C-terminal fragment (Ala405-Lys607; 22.9 kDa) . Hence, limited proteolysis in effect excises most of the GlpO insert (Ser355-Lys404), indicating that this represents a flexible region on the protein surface . The active-site and other spectroscopic properties of the enzyme, including both flavin and tryptophan fluorescence spectra, titration behavior with both dithionite and sulfite, and preferential binding of the anionic form of the oxidized flavin, were largely unaffected by proteolysis . Enzyme-monitored turnover analyses of the intact and nicked streptococcal GlpOs (at {GlpO} approximately 10 microM) demonstrate that the single major catalytic defect in the nicked enzyme corresponds to a 20-fold increase in K(m)(Glp); the basis for this altered kinetic behavior is derived from an 8-fold decrease in the second-order rate constant for reduction of the nicked enzyme, as measured in anaerobic stopped-flow experiments . These results indicate that the flexible surface region represented by elements of the GlpO insert plays an important role in mediating efficient flavin reduction.

Pediatr Infect Dis J, 2000 May, 19(5), 432 - 7
Nonsusceptible Streptococcus pneumoniae in children with chronic otitis media with effusion and recurrent otitis media undergoing ventilating tube placement; Haddad J Jr et al.; CONTEXT: Children with chronic otitis media are at risk for nonsusceptible Streptococcus pneumoniae (NSP) infection . If these children undergo ventilating tube placement, there is an opportunity to culture middle ear fluid and the nasopharynx to determine carriage of NSP . OBJECTIVE: To determine the incidence of NSP carriage, NSP antibiotic susceptibility and risk factors for NSP carriage in children with chronic otitis media undergoing tube placement . DESIGN AND SETTING: Prospective cohort study in an academic medical center with recruitment of patients from an otolaryngology private practice and clinic . PATIENTS: Children < 18 years of age undergoing tube placement for chronic otitis media . INTERVENTIONS: Myringotomy and tube placement, with culture of middle ear fluid and nasopharynx . MAIN OUTCOME MEASURES: The incidence of NSP cultured from the middle ears and nasopharynx of recruited subjects with the use of the minimum inhibitory concentration break points for penicillin susceptibility recommended by the National Committee for Clinical Laboratory Standards . RESULTS: S . pneumoniae was identified in at least 1 site from 23 of 300 study subjects (7.6%); of these 23, 12 case subjects (52.2%) harbored NSP . Of the risk factors assessed by preoperative questionnaire, only younger age was associated with NSP colonization (P < 0.0001) . Of the six oral cephalosporins studied, cefpodoxime and cefuroxime showed good in vitro activity against S . pneumoniae isolates with intermediate penicillin resistance . CONCLUSIONS: Children with chronic otitis media undergoing tube placement may carry NSP and provide a means of monitoring the incidence of NSP and antibiotic susceptibilities for children with ear infections in their communities . Younger age is a risk factor for NSP carriage in this population.

Pediatr Cardiol, 2000 May-Jun, 21(3), 263 - 6
Mycotic pseudoaneurysm of the aorta in children; Barth H et al.; Mycotic pseudoaneurysm of the aorta is a rare disease in childhood . We report on two cases which were diagnosed in an unselected general pediatric population within an 8-month period . The first case was a 16-month-old toddler with a normal cardiac history who presented with purulent pericarditis due to group A streptococcus and subsequent pseudoaneurysm formation of the ascending aorta while convalescing from varicella infection . The second case was a 14-year-old girl with a previously undiagnosed coarctation of the aorta who developed a Staphylococcus aureus aortitis in the dilated poststenotic segment with pseudoaneurysm formation and infiltration into the adjacent lung tissue . In both cases parenteral antibiotic therapy was administered over 10 and 4 days, respectively, followed by emergency surgery consisting of aneurysmectomy, coarctectomy (case 2), and in situ homograft implantation . Recovery was uneventful . In both cases early institution of a femorofemoral cardiopulmonary bypass prevented a fatal outcome despite intraoperative rupture of the pseudoaneurysm.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1754 - 6
Single-oral-dose azithromycin prophylaxis against experimental streptococcal or staphylococcal aortic valve endocarditis; Tsitsika A et al.; Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respectively (P = 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P = 0.018) . Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1749 - 53
Postantibiotic suppression of growth of erythromycin A-susceptible and -resistant gram-positive bacteria by the ketolides telithromycin (HMR 3647) and HMR 3004; Munckhof WJ et al.; We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E(max) model . Mean maximum telithromycin PAEs against erythromycin A-susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae were 3 . 7, 8.9, and 9.7 h, respectively, while maximum PAEs for erythromycin A-resistant strains were much shorter . Mean maximum HMR 3004 PAEs were 3.2 to 4.4 h for all species.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1745 - 8
Identification and characterization of the penicillin-binding protein 2a of Streptococcus pneumoniae and its possible role in resistance to beta-lactam antibiotics; Zhao G et al.; To further understand the role of penicillin-binding protein 2a (PBP 2a) of Streptococcus pneumoniae in penicillin resistance, we confirmed the identity of the protein as PBP 2a . The PBP 2a protein migrated electrophoretically to a position corresponding to that of PBP 2x, PBP 2a, and PBP 2b of S . pneumoniae and was absent in a pbp2a insertional mutant of S . pneumoniae . We found that the affinities of PBP 2a for penicillins were lower than for cephalosporins and a carbapenem . When compared with other S . pneumoniae PBPs, PBP 2a exhibited lower affinities for beta-lactam antibiotics, especially penicillins . Therefore, PBP 2a is a low-affinity PBP for beta-lactam antibiotics in S . pneumoniae.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1575 - 7
Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice; Azoulay-Dupuis E et al.; We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes . Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent . The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype . On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups . In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible . In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%) . In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin . The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%) . These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type . The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1562 - 7
Studies of the novel ketolide ABT-773: transport, binding to ribosomes, and inhibition of protein synthesis in Streptococcus pneumoniae; Capobianco JO et al.; Macrolide resistance in Streptococcus pneumoniae has been associated with two main mechanisms: target modification by Erm methyltransferases and efflux by macrolide pumps . The ketolide ABT-773, which has a 3-keto group and no L-cladinose sugar, represents a new class of drugs with in vitro activity against a variety of resistant bacteria . Several approaches were undertaken to understand how ABT-773 was able to defeat resistance mechanisms . We demonstrated tighter ribosome binding of ABT-773 than erythromycin . We also showed that ABT-773 (i) accumulated in macrolide-sensitive S . pneumoniae at a higher rate than erythromycin, (ii) was able to bind with methylated ribosomes, though at lower affinities than with wild-type ribosomes, and (iii) accumulated in S . pneumoniae strains with the efflux-resistant phenotype.

Antimicrob Agents Chemother, 2000 Jun, 44(6), 1453 - 7
Resistance to macrolides in Streptococcus pyogenes in France in pediatric patients; Bingen E et al.; A total of 1,500 recent throat isolates of Streptococcus pyogenes collected between 1996 and 1999 from children throughout France were tested for their susceptibility to erythromycin, azithromycin, josamycin, clindamycin, and streptogramin B . The erythromycin-resistant isolates were further studied for their genetic mechanism of resistance, by means of PCR . The clonality of these strains was also investigated by means of serotyping and ribotyping . In all, 6.2% of the strains were erythromycin resistant, and 3.4 and 2.8% expressed the constitutive MLS(B) and M resistance phenotypes and harbored the ermB and mefA genes, respectively; ermTR was recovered from one isolate which also harbored the ermB gene . Ten serotypes and 8 ribotypes were identified, but we identified 17 strains by combining serotyping with ribotyping . Among the eight ribotypes, the mefA gene was recovered from six clusters, one being predominant, while the ermB gene was recovered from four clusters, of which two were predominant.

Infect Immun, 2000 Jun, 68(6), 3740 - 3
Detection of 23 immunogenic pneumococcal proteins using convalescent-phase serum; Zysk G et al.; A genomic expression library of Streptococcus pneumoniae was screened with a convalescent-phase serum for immunoreactive proteins . Six known and 17 unknown pneumococcal proteins were detected . Five of the known proteins were surface-located virulence factors, and eight of the unknown proteins were putative membrane proteins.

Infect Immun, 2000 Jun, 68(6), 3716 - 9
Replacement of histidine 340 with alanine inactivates the group A Streptococcus extracellular cysteine protease virulence factor; Gubba S et al.; Streptococcus pyogenes expresses a highly conserved extracellular cysteine protease that is a virulence factor for invasive disease, including soft tissue infection . Site-directed mutagenesis was used to generate a His340Ala recombinant mutant protein that was made as a stable 40-kDa zymogen by Escherichia coli . Purified His340Ala protein was proteolytically inactive when bovine casein and human fibronectin were used as substrates . Wild-type 28-kDa streptococcal protease purified from S . pyogenes processed the 40-kDa mutant zymogen to a 28-kDa mature form, a result suggesting that the derivative protein retained structural integrity . The data are consistent with the hypothesis that His340 is an enzyme active site residue, an idea confirmed by recent solution of the zymogen crystal structure (T . F . Kagawa, J . C . Cooney, H . M . Baker, S . McSweeney, M . Liu, S . Gubba, J . M . Musser, and E . N . Baker, Proc . Natl . Acad . Sci . USA 97:2235-2240, 2000) . The data provide additional insight into structure-function relationships in this S . pyogenes virulence factor.

Infect Immun, 2000 Jun, 68(6), 3630 - 4
Pyrogenic toxin superantigen site specificity in toxic shock syndrome and food poisoning in animals; Schlievert PM et al.; Staphylococcus aureus and Streptococcus pyogenes express pyrogenic toxin superantigens (PTSAgs) that are associated with toxic shock syndrome (TSS) and staphylococcal food poisoning (SFP) . Most PTSAgs cause TSS in deep-tissue infections, whereas only TSS toxin 1 (TSST-1) is associated with menstrual, vaginal TSS . In contrast, SFP has been linked only with staphylococcal enterotoxins (SEs) . Because of the differential abilities of PTSAgs to cause systemic or localized symptoms in a site-dependent manner, the present study was undertaken to assess the toxins' abilities to cross mucosal barriers . The activity of three PTSAgs when delivered orally, vaginally, or intravenously to rabbits and orally to monkeys was investigated . TSST-1 induced shock via all three routes in rabbits . Although active when administered intravenously, SEC1 and streptococcal pyrogenic exotoxin A (SPEA) did not cause symptoms when administered orally or vaginally . Only SEC1 induced emesis in the monkey feeding assay . TSST-1, albeit less stable than SEC1 and SPEA to pepsin, induced diarrhea in monkeys . Our results may explain the unique association of TSST-1 with menstrual TSS and why SPEA is only rarely associated with TSS after pharyngitis, despite being highly associated with TSS after subcutaneous infections . Finally, our studies indicate that enterotoxicity in SFP is not the result of superantigenicity.

Infect Immun, 2000 Jun, 68(6), 3523 - 34
Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases; Chatellier S et al.; The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods . All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases . All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype, speA(+) speB(+) speC speF(+) speG(+) speH smeZ(+) ssa . All isolates had the same speA allotype, speA2 . The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band . A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity . Likewise, although the phenotypic expression of SpeA, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity . Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens were very similar for isolates from severe and nonsevere cases (P > 0.1) . Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals . These findings underscore the contribution of host factors to the outcome of invasive GAS infections.

Infect Immun, 2000 Jun, 68(6), 3226 - 32
Streptococcal erythrogenic toxin B abrogates fibronectin-dependent internalization of Streptococcus pyogenes by cultured mammalian cells; Chaussee MS et al.; Streptococcus pyogenes secretes several proteins that influence host-pathogen interactions . A tissue-culture model was used to study the influence of the secreted cysteine protease streptococcal erythrogenic toxin B (SPE B) on the interaction between S . pyogenes strain NZ131 (serotype M49) and mammalian cells . Inactivation of the speB gene enhanced fibronectin-dependent uptake of the pathogen by Chinese hamster ovary (CHO-K1) cells compared to that in the isogenic wild-type strain . Preincubation of the NZ131 speB mutant with purified SPE B protease significantly inhibited fibronectin-dependent uptake by both CHO-K1 and CHO-pgs745 cells . The effect was attributed to an abrogation of fibronectin binding to the surface of the bacteria that did not involve either the M49 protein or the streptococcal fibronectin-binding protein SfbI . In contrast, pretreatment of the NZ131 speB mutant with SPE B did not influence sulfated polysaccharide-mediated uptake by CHO-pgs745 cells . The results indicate that the SPE B protease specifically alters bacterial cell surface proteins and thereby influences pathogen uptake.

Infect Immun, 2000 Jun, 68(6), 3153 - 7
Inhibition of leukocyte entry into the brain by the selectin blocker fucoidin decreases interleukin-1 (IL-1) levels but increases IL-8 levels in cerebrospinal fluid during experimental pneumococcal meningitis in rabbits; Ostergaard C et al.; The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis . In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8 into the CSF was investigated . Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of approximately 10(6) CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7) . CSF samples were obtained every second hour during a 16-h study period . Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively; P < 0.02) . A less consistent decrease in CSF TNF-alpha levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05) . In contrast, there was no attenuation in CSF IL-8 levels . Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively; P < 0.09) . In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-alpha into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

Endod Dent Traumatol, 1999 Aug, 15(4), 171 - 4
In vitro antibacterial effect of RC-Prep components on Streptococcus sobrinus; Steinberg D et al.; The aim of this study was to examine the bacteriostatic and bactericidal effects of the components of RC-Prep: EDTA, urea peroxide and glycol . The minimal inhibitory concentration and the minimal bactericidic concentration of EDTA, urea peroxide and glycol were tested on the viability of Streptococcus sobrinus (S . sobrinus) . The combined antibacterial effect of these components was also examined on S . sobrinus . The minimal inhibitory concentration of EDTA was found to be 0.125%, of urea peroxide 0.25%, and of glycol 30% . The minimal bactericidic concentration of EDTA was 0.25%, of urea peroxide 0.5% and of glycol 50% . An antibacterial synergistic effect was found between specific combinations of urea peroxide, EDTA and glycol . No antagonistic effects were found in the various combinations between the components . The antimicrobial effect of the components of RC-Prep was enhanced in specific combinations of the ingredients . This effect might contribute to the intracanal cleansing properties of this medication.

Proteins, 2000 Jul 1, 40(1), 126 - 34
Characterization of the active site of group B streptococcal hyaluronan lyase; Pritchard DG et al.; Hyaluronan lyase is secreted by most strains of the human pathogen, group B streptococcus . Site-directed mutagenesis of the enzyme identified three amino acid residues important for enzyme activity, H479, Y488, and R542 . These three residues are in close proximity in the putative active site of a homology model of group B streptococcal hyaluronan lyase . The homology model was based on the crystal structure of another related glycosaminoglycan lyase, chondroitin AC lyase, which exhibits different substrate specificity . Two asparagine residues in the active site groove, N429 and N660, were also found to be essential for enzyme activity . In addition, conversion of two adjacent tryptophan residues in the groove to alanines abolished activity . All amino acids found to be essential in GBS hyaluronan lyase are conserved in both enzymes . However, several amino acids in the active site groove of the two enzymes are not conserved . In the 18 cases in which one of these amino acids in GBS hyaluronan lyase was replaced with its corresponding amino acid in chondroitin AC lyase, no major loss of activity or change in substrate specificity was observed .

J Biomed Mater Res, 2000 Jul, 51(1), 123 - 7
Effects of resin composite components on glucosyltransferase of cariogenic bacterium; Kawai K et al.; The aim of our study was to investigate the effect of resin composite components on glucan synthesis by glucosyltransferase (GTase) derived from a cariogenic bacterium, Streptococcus sobrinus B13 . The eluates from cured composites stored in 0.05 mol/L potassium phosphate buffer (KPB) (pH 6.8) for 2 weeks at 37 degrees C stimulated the formation of water-insoluble glucan, whereas those from amalgam inhibited it . This finding suggests that the eluates from the resin composites enhance GTase activity and contribute to plaque formation . In the individual resin components, a diglycidyl methacrylate and triethylene glycol dimethacrylate significantly enhanced GTase activity . However, most polymerization inhibitors and accelerators were potent inhibitors of enzyme activity . Thus, GTase stimulation by eluates from resin composites is hypothesized to be heavily dependent on the effect of the eluated resin monomers, even though the other eluting components had inhibitory effects on GTase .

Vaccine, 2000 Jun 15, 18(25), 2895 - 901
Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model; Lipsitch M et al.; Widespread use of conjugate vaccines against Streptococcus pneumoniae, by reducing carriage of S . pneumoniae serotypes included in the vaccine, may result in an increase in nasopharyngeal carriage of - and disease from - nonvaccine serotypes of the same species . Mathematical models predict that the extent of such replacement will depend positively on the degree to which carriage of vaccine-type S . pneumoniae inhibits acquisition of nonvaccine-type pneumococci, and may depend negatively on the inhibition of vaccine-type pneumococci by nonvaccine-type pneumococci . We used a mouse model of intranasal carriage of pneumococci to test whether such inhibition occurs between different pneumococcal strains . Mice carrying a streptomycin-resistant derivative of S . pneumoniae BG9163 (serotype 6B) as a resident strain showed reduced levels of colonization when challenged intranasally by optochin-resistant derivatives of the same strain and of a serotype 23F pneumococcus, BG8826 . Inhibition could be overcome by increasing the dose of the challenge strain . Carriage of optochin-resistant BG9163 did not inhibit acquisition of the streptomycin-resistant variant . Colonization by a challenge strain did not significantly affect the level of colonization with the resident strain . These results provide evidence that is consistent with several hitherto untested assumptions of mathematical models of serotype replacement and suggest that a biological mechanism exists that could account for serotype replacement that is observed in clinical trials . The findings provide a basis for further studies of in vivo interactions between strains of S . pneumoniae.

Proc Natl Acad Sci U S A, 2000 May 23, 97(11), 6031 - 6
Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse; Mi QS et al.; Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn) . T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection . The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial . We generated V1(-/-) knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene . No anti-PC Abs were produced in V1(-/-) mice immunized with avirulent SPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice . These Abs provided poor protection against virulent SPn; thus, <25% of V1(-/-) mice survived challenge with 10(4) bacteria as compared with 100% survival of V1(+/+) mice . The anti-PC Abs in V1(-/-) mice were heteroclitic, binding to nitrophenyl-PC better than to PC . None of nine hybridomas produced from V1(-/-) mice provided passive protection . However, the V1(-/-) mice produced normal amounts of Ab to SPn proteins that can partially protect mice against SPn . These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn, and the V1(-/-) mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection.

J Exp Med, 2000 May 15, 191(10), 1765 - 76
The streptococcal superantigen SMEZ exhibits wide allelic variation, mosaic structure, and significant antigenic variation; Proft T et al.; The frequencies of the newly identified streptococcal superantigen genes smez, spe-g, and spe-h were determined in a panel of 103 clinical isolates collected between 1976 and 1998 at various locations throughout New Zealand . smez and spe-g were found in every group A Streptococcus (GAS) isolate, suggesting a chromosomal location . The spe-h gene was found in only 24% of the GAS isolates and is probably located on a mobile DNA element . The smez gene displays extensive allelic variation and appears to be in linkage equilibrium with the M/emm type . 22 novel smez alleles were identified from 21 different M/emm types in addition to the already reported alleles smez and smez-2 with sequence identities between 94 . 5 and 99.9% . Three alleles are nonfunctional due to a single base pair deletion . The remaining 21 alleles encode distinct SMEZ variants . The mosaic structure of the smez gene suggests that this polymorphism has arisen from homologous recombination events rather than random point mutation . The recently resolved SMEZ-2 crystal structure shows that the polymorphic residues are mainly surface exposed and scattered over the entire protein . The allelic variation did not affect either Vbeta specificity or potency, but did result in significant antigenic differences . Neutralizing antibody responses of individual human sera against different SMEZ variants varied significantly . 98% of sera completely neutralized SMEZ-1, but only 85% neutralized SMEZ-2, a very potent variant that has not yet been found in any New Zealand isolate . SMEZ-specific Vbeta8 activity was found in culture supernatants of 66% of the GAS isolates, indicating a potential base for the development of a SMEZ targeting vaccine.

Chemotherapy, 2000, 46 Suppl 1, 6 - 14
Pharmacodynamics and pharmacokinetics of levofloxacin; Nightingale CH et al.; Principles of antibiotic pharmacodynamics include factors that are important for effective eradication of bacteria as well as the suppression of resistance . For effective eradication of bacteria and a good clinical outcome, a ratio for the area under the plasma concentration-time curve relative to the minimum inhibitory concentration (AUC/MIC) of greater than 100 is needed for gram-negative organisms, and a level of greater than 30 is required for gram-positive organisms . Pharmacodynamic principles can also be used to devise the optimal administration regimen for specific antimicrobial agents . Pharmacodynamic analysis of the activity of levofloxacin against Streptococcus pneumoniae revealed that, 99% of the time, actual hospitalized patients achieve an AUC/MIC of greater than 30 . This indicates that levofloxacin will be very effective in treating S . pneumoniae infections in the majority of patients . Cost of treatment is an increasing concern voiced by healthcare providers and users alike . This has led to a much greater emphasis placed upon the cost of individual drugs used in the management of infections . However, when evaluating the cost of an antibiotic, it is extremely important that not only are the direct acquisition costs assessed, but consideration also given to other aspects incurring a financial burden, such as drug preparation cost, supplies, costs of treating adverse events or any treatment failures . It is only by having such a full assessment of costs that realistic financial comparisons can be made between different antibiotics.

Vet Microbiol, 2000 Jun 1, 74(3), 273 - 80
Adhesion of Streptococcus gallolyticus strains to extracellular matrix proteins; Vanrobaeys M et al.; Fourteen pigeon Streptococcus gallolyticus strains of differing virulence, were tested for their ability to adhere to immobilised fibronectin, collagen types I, III and IV . Eight, 2 and 13 strains were able to bind fibronectin, collagen types III and IV, respectively . None of the strains adhered to collagen type I . Heat treatment, proteolytic digestion or periodate treatment reduced the binding of S . gallolyticus to fibronectin and collagen type IV, suggesting that surface receptors contain proteins and carbohydrates . Although binding to these extracellular matrix proteins can play a role in the pathogenesis of streptococcosis in pigeons, binding properties could not be related to virulence, indicating that other factors determine differences in virulence among pigeon S . gallolyticus strains . Adhesion to collagen type IV may account in part for the distribution pattern of the lesions observed in naturally and experimentally infected pigeons.

Vet Microbiol, 2000 Jun 1, 74(3), 237 - 48
Distribution of capsular types and production of muramidase-released protein (MRP) and extracellular factor (EF) of Streptococcus suis strains isolated from diseased pigs in seven European countries; Wisselink HJ et al.; Streptococcus suis strains (n=411), isolated from diseased pigs in seven European countries were serotyped using specific antisera against serotype 1 to 28, and were phenotyped on the basis of their muramidase-released-protein (MRP) and extracellular-factor protein (EF) production . Overall, S . suis serotype 2 appeared to be most prevalent (32%), followed by serotype 9 (20%) and serotype 1 (12%) . Serotype 2 was most frequently isolated in France, Italy and Spain, whereas serotype 9 was most frequently isolated in Belgium, The Netherlands and Germany . In the United Kingdom serotypes 1 and 14 were most frequently isolated . High percentages of S . suis serotype 1, 2, 1/2 and 14 strains, isolated from tissues associated with S . suis infections such as brain, serosa, joint, heart and organs expressed the EF-protein, indicating that in these serotypes expression of EF is likely to be associated with virulence . In contrast, strains belonging to serotype 7 and 9, isolated from tissues associated with S . suis infections did not produce EF . These results strongly suggest that in the serotypes 7 and 9 EF expression is not related to virulence . More than 80% of the S . suis serotype 9 strains produced an MRP* protein, a high molecular variant of the 136kDa MRP . Expression of MRP* in serotype 9 strains is possibly associated with virulence.

Biol Psychiatry, 2000 May 15, 47(10), 851 - 7
On defining Sydenham's chorea: where do we draw the line?
Murphy TK, Goodman WK, Ayoub EM, Voeller KK.
Sydenham's chorea (SC) is a major manifestation of rheumatic fever characterized by an array of neuropsychiatric symptoms that vary in severity, timing, and character . Some of the same symptoms are seen in Tourette's syndrome and childhood-onset obsessive-compulsive disorder . Genetic vulnerability appears to play a role in all three conditions . The term PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcus) has been introduced to describe a putative subset of obsessive-compulsive disorder and Tourette's syndrome that bears some resemblance to Sydenham's chorea . This article discusses whether PANDAS should be subsumed under Sydenham's chorea, thus expanding the diagnostic boundaries of Sydenham's chorea to include primarily neuropsychiatric presentations now classified as cases of obsessive-compulsive disorder or Tourette's syndrome . We conclude that PANDAS is a useful construct, but that it would be premature to view it as a subset of Sydenham's chorea-whether defined narrowly or broadly.

Chest, 2000 May, 117(5), 1515 - 6
Pneumococcal bacteremia associated with an infected central venous catheter; Dhillon SS et al.; Pneumococcus (Streptococcus pneumoniae) bacteremia is a serious infection . Pneumococcus has never been implicated as a cause of a central venous catheter-related bacteremia . It has been isolated from the catheter tip only twice before, and in one case caused the infection of an infusion port device . We report case of a 41-year-old woman who developed pneumococcal bacteremia after 6 days of an indwelling central venous catheter . The catheter tip grew > 300 cfu of S pneumoniae by the roll-plate method described by Maki and colleagues . No other focus of infection could be found in this patient . To the best of our knowledge, this is the first reported case of pneumococcal bacteremia associated with an infected central venous catheter.

Rinsho Byori, 2000 Jan, Suppl 111, 125 - 31
{Infections with drug resistant bacteria and their treatment methods--PRSP infections}; Kuroki H; S . pneumoniae is one of the most important pathogens in respiratory tract infections and systemic infections . The frequencies of isolating Penicillin-resistant Streptococcus pneumoniae(PRSP) has been increasing recently . The therapeutic strategy is becoming difficult . Ampicillin and amoxicillin are the choices of drugs to treat respiratory infections with intermediate strains . Panipenem may be the first choice of treatment for systemic infections . Administration of vancomycin should also be considered . Judicious use of antimicrobials is necessary to avoid the spread of multi-resistant strains . In some cases physical therapy would be recommended.

Rinsho Byori, 2000 Jan, Suppl 111, 48 - 55
{The procedures for detection of penicillin-resistant Streptococcus pneumoniae and the epidemiology}; Oguri T et al.; Penicillin-resistant Streptococcus pneumoniae was first described in South Africa in 1977 and soon afterward was reported in other countries and in Japan . According to NCCLS standards for antimicrobial susceptibility tests, in vitro activity of S . pneumoniae is the best procedure using the minimum inhibitory concentration method . Benzylpenicillin, cefotaxime or ceftriaxone, and meropenem should be tested by a reliable MIC method and the susceptibility should be reported in the case isolated from blood and/or cerebrospinal fluid . Using the oxacillin test, it is difficult to distinguish penicillin-resistant from intermediate strains or sometimes susceptible strains.

FEMS Microbiol Lett, 2000 May 15, 186(2), 187 - 91
Construction of region-specific partial duplication mutants (merodiploid mutants) to identify the regulatory gene for the glucan-binding protein C gene in vivo in Streptococcus mutans; Sato Y et al.; The gbpC gene encoding the glucan-binding protein C which is involved in dextran (glucan)-dependent aggregation (ddag) of Streptococcus mutans has been identified by random mutagenesis . We analyzed ddag(-) mutants containing the intact gbpC gene and found that these mutants possessed a large and characteristic duplication of a region of the chromosome which was responsible for the phenotype . Based upon characterization of these duplications, we developed a strategy to introduce a duplication into any specific region of the chromosome of these organisms . The 690-bp gene responsible for the ddag(-) phenotype was identified within a 60-kb region by observing ddag (positive or negative) phenotypes of successively constructed specific duplication mutants.

J Microbiol Methods, 2000 May, 40(3), 225 - 32
Dot assay for determining adhesive interactions between yeasts and bacteria under controlled hydrodynamic conditions; Millsap KW et al.; Candida belongs to the normal human microflora and are found adhering to a number of human body tissues as well as to a variety of biomaterials implants . Often, yeasts adhere in association with bacteria, but to date there is no definitive assay to investigate adhesive interactions between yeasts and bacteria adhering on surfaces . Although we recently described the use of a parallel plate flow chamber to this purpose {Millsap, K.W., Bos, R., Van der Mei, H . C., Busscher, H.J., 1998 . Adhesive interactions between medically important yeasts and bacteria . FEMS Microbiol . Rev . 21, 321-336}, the method was slow and evaluation of a large number of strains showed major biological variation between experiments . Here, we describe a new assay for the simultaneous determination of the adhesive interactions between yeasts and different bacterial strains on a surface under controlled hydrodynamic conditions . On an acrylic surface, the presence of adhering bacteria suppressed adhesion of Candida albicans ATCC 10261 to various degrees, depending on the bacterial strain involved . Suppression of C . albicans ATCC 10261 adhesion was strongest by Actinomyces naeslundii T14V-J1, while adhering Streptococcus gordonii NCTC 7869 caused the weakest suppression of yeast adhesion . When adhering yeasts and bacteria were challenged with the high detachment force of a passing liquid-air interface, the majority of the yeasts detached, while C . albicans adhering on the control, bare polymethylmethacrylate surface formed aggregates . Summarizing, this study presents a new method to determine suggested adhesive interactions between yeasts and adhering bacteria under controlled hydrodynamic conditions . However, the results seem to indicate that these adhesive interactions may well not exist, but that instead different bacterial strains have varying abilities to discourage yeast adhesion.

J Immunol, 2000 May 15, 164(10), 5328 - 36
Human C4b-binding protein has overlapping, but not identical, binding sites for C4b and streptococcal M proteins; Blom AM et al.; Many strains of Streptococcus pyogenes bind C4b-binding protein (C4BP), an inhibitor of complement activation . The binding is mediated by surface M proteins in a fashion that has been suggested to mimic the binding of C4b . We have previously shown that a positively charged cluster at the interface between complement control protein domains 1 and 2 of C4BP alpha-chain is crucial for the C4b-C4BP interaction . To extend this observation, and to investigate the interaction with M proteins, we constructed and characterized a total of nine mutants of C4BP . We identified a key recognition surface for M proteins that overlaps with the C4b binding site because substitution of R64 and H67 by Gln dramatically reduces binding to both ligands . However, the analysis of all mutants indicates that the binding sites for C4b and M proteins are only overlapping, but not identical . Furthermore, M proteins were able to displace C4BP from immobilized C4b, whereas C4b only weakly affected binding of C4BP to immobilized M proteins . We found that the molecular mechanisms involved in these two interactions differ because the binding between M proteins and C4BP is relatively insensitive to salt in contrast to the C4BP-C4b binding . In addition, six mAbs directed against the alpha-chain interfered with C4b-C4BP interaction, whereas only two of them efficiently inhibited binding of C4BP to M proteins . Collectively, our results suggest that binding between C4b and C4BP is governed mostly by electrostatic interactions, while additional noncovalent forces cause tight binding of C4BP to streptococcal M proteins.

FEMS Immunol Med Microbiol, 2000 Jun, 28(2), 121 - 8
Molecular cloning, purification and immunological responses of recombinants GroEL and DnaK from Streptococcus pyogenes; Lemos JA et al.; To better understand the roles of heat shock proteins in streptococcal diseases, the groEL and dnaK genes from Streptococcus pyogenes were cloned and their products (GroEL and DnaK) and derivatives (F2GroEL, F3GroEL and C1DnaK) purified as His-tagged fusion proteins . Western blot analysis of the purified proteins with sera from individuals with streptococcal diseases demonstrated that 29 out of 36 sera tested were reactive with GroEL and eight recognized DnaK . Rabbit antiserum against myosin recognized both GroEL and DnaK . Antibodies raised against purified F2GroEL and DnaK reacted with myosin in the ELISA but not in a Western immunoblot . These data indicate that the S . pyogenes GroEL and DnaK may be important immunogens during streptococcal infections . Furthermore, we provide evidence of an immunogenic relatedness of the GroEL and DnaK proteins with myosin that could play a role in the pathogenesis of streptococcal non-suppurative sequelae.

Clin Diagn Lab Immunol, 2000 May, 7(3), 490 - 6
Specificity and prevalence of natural bovine anti-alpha galactosyl (Galalpha1-6Glc or Galalpha1-6Gal) antibodies; Ni Y et al.; Immunity against the carbohydrate components of microorganisms mediated by antibodies is an important part of host defenses . Humans and closely related primates, but not other mammals, possess natural anti-Galalpha1-3Gal antibodies which also, although less avidly, react with melibiose (Galalpha1-6Glc) . Using an enzyme-linked immunosorbent assay (ELISA) with melibiose-bovine serum albumin as an antigen, we analyzed bovine anti-alpha galactosyl antibodies with respect to specificity and distribution in individual animals . Inhibition assays showed that melibiose was the strongest inhibitor, followed equally by stachyose (Galalpha1-6Galalpha1-6Glcbeta1-2Fru) and raffinose (Galalpha1-6Glcbeta1-2Fru) and then by Galbeta1-6Gal, Gal, and Galalpha1-2Gal . Others, including Galalpha1-3Gal and Galalpha1-4Gal, only exhibited minor inhibition . Thus, these bovine anti-alpha galactosyl antibodies appeared to preferentially react with Galalpha1-6Glc or Galalpha1-6Gal . The distinction of this specificity from that (Galalpha1-3Gal) of human antibodies was further demonstrated by the poor reaction of bovine serum to the Galalpha1-3Gal antigen in comparison to human serum . All 27 healthy bovine serum samples of the three age groups (newborn, calf, and adult) tested contained such antibodies with titers increasing with age . The antibodies purified by affinity chromatography using a melibiose-agarose column were mainly of the immunoglobulin G (IgG) isotype with a concentration of >23 microg/ml in most samples . IgG1 was found to be the primary antimelibiose IgG isotype in all age groups by isotype-specific ELISA, but a significant increase in IgG2, an isotype more related to innate immunity, was observed in calves and adults, compared to newborns . The purified antibodies reacted with the type II bovine strain of Streptococcus agalactiae, a common pathogen of bovine mastitis . Thus, these anti-Galalpha1-6Glc or Galalpha1-6Gal antibodies in cattle might be involved in defense against microbes bearing this or the related epitopes.

Clin Diagn Lab Immunol, 2000 May, 7(3), 486 - 9
A latex bead-based flow cytometric immunoassay capable of simultaneous typing of multiple pneumococcal serotypes (Multibead assay); Park MK et al.; A simple and rapid method of simultaneously determining 15 Streptococcus pneumoniae serotypes was developed . Fifteen latex beads of different sizes and different red fluorescence levels were coated with 1 of 15 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9N, 9V, 14, 18C, 19A, 19F, 22F, and 23F) of pneumococcal capsular polysaccharide (PS) . The bead mixture was incubated with individual pneumococcal lysate, a pool of rabbit antisera capable of binding the 15 serotypes, and fluorescein (green fluorescence)-conjugated anti-rabbit antibody . Bead size, red fluorescence, and green fluorescence were measured in a single flow cytometer run . The green fluorescence of the beads was inhibited only when there was a serotypic match between PS on the bead and PS in the pneumococcal lysate . This method distinguished cross-reactive serotypes and correctly identified the serotypes in 100% of 86 pneumococcal isolates tested.

Dakar Med, 1998, 43(2), 198 - 200
{Staphylococcus aureus purulent pleurisy in children . Experience of the Albert Royer Hospital for Children of the Fann University Hospital Center in Dakar}; Ndiaye O et al.; The authors report here by a retrospective study 58 cases of Staphylococcus aureus empyema at Albert ROYER child hospital located in the Fann University Teaching Hospital of Fann between January 1st 1992 and December 31, 1995 . In this study staphylococcus aureus is the bacterium involved in pleural effusions of the children (54%) a long way ahead Streptococcus pneumoniae (16%) . Infant less than 30 month is more affected (86%) . The average age of the patients is 16.8 month +/- 16.6 . The resistance of the germ to usual antibiotics, the precariousness of the research field and mechanical complications linked to the outpouring explain their seriousness . The treatment lies upon an adapted antibiotic and bactericidal therapy associated to closed chest tube drainage.

J Antimicrob Chemother, 2000 May, 45(5), 623 - 31
Streptococcus pneumoniae in the USA: in vitro susceptibility and pharmacodynamic analysis; Mason EO Jr et al.; Ninety-two laboratories in the USA submitted isolates of Streptococcus pneumoniae to a single laboratory for susceptibility testing . Overall, 64% of 4489 isolates were susceptible to penicillin, 24% were intermediate and 13% were resistant to penicillin, although susceptibilities varied depending on geographical region . Macrolide/azalide resistance varied from 4 to 30%, with some regions having macrolide/azalide resistance higher than penicillin resistance . Children 12 years of age were significantly more likely to be infected with a penicillin-resistant pneumococcus than were adolescents or adults . Isolates from the respiratory tract were more likely to be penicillin resistant and >50% of pneumococci from the ear were resistant to penicillin . Almost 25% of penicillin-susceptible isolates had cefaclor MICs 2.0 mg/L and 15% of penicillin-susceptible isolates had loracarbef MICs 2.0 mg/L . These isolates would be erroneously reported as susceptible using NCCLS guidelines, and this finding may explain the lack of clinical response in patients treated with these antibiotics . The predicted plasma concentrations of all cephalosporins tested exceeded the geometric mean MIC for at least 40% of the dosing interval for penicillin-susceptible S . pneumoniae; for penicillin-intermediate S . pneumoniae, only cefprozil (56%), cefuroxime (64%) and cefpodoxime (63%) reached >40% of time above the geometric mean MIC in the dosing interval . None of the cephalosporins evaluated achieved a substantial time above the geometric mean MIC during its dosing interval for fully penicillin-resistant S . pneumoniae.

J Antimicrob Chemother, 2000 May, 45(5), 605 - 9
High prevalence of erythromycin-resistant, clindamycin/miocamycin-susceptible (M phenotype) Streptococcus pyogenes: results of a Spanish multicentre study in 1998 . Spanish Group for the Study of Infection in the Primary Health Care Setting; Alos JI et al.; Using the standard agar dilution method we studied the prevalence of susceptibility to 14-, 15- and 16-membered ring macrolides and clindamycin in Streptococcus pyogenes isolated in 1998 from 21 laboratories in Spain . The number of strains admitted to the study was proportional to the numbers of inhabitants in each geographical area . We also determined the susceptibility phenotypes and the genetic basis for the antibiotic resistance . A total of 486 unduplicated isolates of S . pyogenes were used . Throat swab samples provided 359 (73.9%) isolates, and the remaining 127 isolates were from other sources . One hundred and fourteen (23.5%) isolates were resistant to erythromycin, a 14-membered ring macrolide, and azithromycin, a 15-membered macrolide, whereas only 1% of isolates were resistant to miocamycin, a 16-membered macrolide and 0.8% were resistant to clindamycin . Of the 114 erythromycin-resistant strains, 109 (95.6%) were susceptible to clindamycin and miocamycin . Since induction with erythromycin did not modify susceptibility to the latter antibiotics, these 109 strains were considered to have the M phenotype . Twenty strains with the M phenotype, one per laboratory, were assayed by PCR and showed the presence of the mef gene, which is responsible for antibiotic resistance by an efflux system . Among comparable studies covering entire countries, ours demonstrates one of the highest rates of S . pyogenes erythromycin resistance and clindamycin and miocamycin susceptibility in the world . Strains with the M phenotype account for the great majority of these isolates.

J Antimicrob Chemother, 2000 May, 45(5), 583 - 90
Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones; Pestova E et al.; The in vitro activity of the novel 8-methoxyquinolone, moxifloxacin, against Streptococcus pneumoniae was evaluated, and the intracellular targets of this agent were studied . Analysis of mutant strains selected with moxifloxacin demonstrated that first-step mutants bore amino acid substitutions at position 81 in the GyrA subunit of DNA gyrase . This suggests that, unlike older fluoroquinolone agents such as ciprofloxacin and levofloxacin, but similar to other C-8 substituted quinolones like sparfloxacin and gatifloxacin, moxifloxacin targets the GyrA subunit of DNA gyrase as an initial lethal event . Such a mechanism results in high activity against increasingly common S . pneumoniae strains bearing substitutions in DNA topoisomerase IV . Moxifloxacin was active with an MIC of </= 0.25 mg/L against S . pneumoniae clinical isolates, and against mutants, selected in the laboratory with ciprofloxacin or levofloxacin, that bore a Ser-79-->Phe/Tyr substitution in ParC . The moxifloxacin MIC for strains with mutations in the structural genes for both DNA gyrase subunit GyrA and DNA topoisomerase IV subunit ParC did not exceed 2 mg/L, a level within clinically achievable serum concentrations for this agent . We also found that moxifloxacin is a poor substrate for active efflux in S . pneumoniae . Therefore, the high activity of moxifloxacin against S . pneumoniae appears to be a result of both enhanced activity against DNA gyrase and topoisomerase IV, and reduced efflux from the bacterial cell.

Zhonghua Wai Ke Za Zhi, 1997 Nov, 35(11), 663 - 6
{Detection of bacterial DNA from cholesterol gallstones by NP-PCR and its clinical significance}; Wu X et al.; To search for bacterial DNA sequences in cholesterol gallstones with negative bacterial culture . We used nested primers polymerase chain reaction (NP-PCR) technique to amplify bacterial gene fragments were amplified in vitro from DNA extracted from cholesterol gallstones . Comparative 16S ribosomal RNA sequence analysis was used for elucidation of bacterial identification . The gallbladder gallstones of 30 patients were analyzed . Bacterial DNA was found in the stones of 26 patients . There was no difference either in cholesterol and water content or in harboring bacterial DNA of gallstones . E . coli-related DNA fragments were found in the stones of 8 patients (26.67%) . Propionibacteria type DNA was found in the stones of 7 patients (23.33%) . Stones of 2 patients (6.67%) harbored bacterial gene fragments with similarity of Streptococcus pyogenes . A more heterogeneous sequence collection was found in 7 patients (23.33%) and could be assigned to the multiple bacterial infections . Another stones of 2 patients (6.67%) had bacterial DNA with lower molecularweight which might be related to some unidentified bacteria . The results suggested that most cholesterol gallstones harbor bacterial DNA . It is important to determine whether these microorganisms are innocent bystanders or active participants in cholesterol gallstone formation.

Cochrane Database Syst Rev . 2000;(2):CD000023.
Antibiotics for sore throat; Del Mar CB et al.; BACKGROUND: Sore throat is a very common reason for people to attend for medical care . Sore throat is a disease that remits spontaneously, that is, 'cure' is not dependant on treatment . Nonetheless primary care doctors commonly prescribe antibiotics for sore throat and other upper respiratory tract infections . OBJECTIVES: To assess the benefits of antibiotics in the management of sore throat . SEARCH STRATEGY: Systematic search of the literature from 1945 to 1999, using electronic searches of MEDLINE (using the keywords, "pharyngitis", "sore throat" and "tonsillitis") after 1966, the Cochrane Library, the Cochrane collection of hand-searched trials, and the reference sections of the articles identified . Abstracts of identified articles were used to determine which studies were trials . SELECTION CRITERIA: Trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache or fever), or complications (suppurative and non-suppurative) of sore throat . DATA COLLECTION AND ANALYSIS: RevMan 4.0.3 MAIN RESULTS: A total number of 10,484 cases of sore throat have been studied . 1 . Non-suppurative complications There was a trend for protection against acute glomerulonephritis by antibiotics, but insufficient cases were recorded to be sure of this effect . Several studies found benefit from antibiotics for acute rheumatic fever, which reduced this complication to less than one third (OR = 0.30; 95% CI = 0.20-0.45) . 2 . Suppurative complications Antibiotics reduced the incidence of acute otitis media to about one quarter of that in the placebo group (OR = 0.22; 95% CI = 0.11-0.43) and reduced the incidence of acute sinusitis to about one half of that in the placebo group (OR = 0.46; 95% CI = 0.10-2.05) . The incidence of quinsy was also reduced in relation to placebo group (OR = 0.18; 95% CI = 0.08-0.43) . 3 . Symptoms Symptoms of headache, throat soreness and fever were reduced by antibiotics to about one half . The greatest time for this to be evident was at about three and a half days (when the symptoms of about 50% of untreated patients had settled) . About 90% of treated and untreated patients were symptom-free by one week . 4 . Subgroup analyses of symptom reduction Subgroup analysis by age; blind vs unblinded; us of antipyretics; or results of swabs for Streptococcus yielded no significant differences . REVIEWER'S CONCLUSIONS: Antibiotics confer relative benefits in the treatment of sore throat . However, the absolute benefits are modest . Protecting sore throat sufferers against suppurative and non-suppurative complications in modern Western society can only be achieved by treating many with antibiotics who will derive no benefit . Antibiotics shorten the duration of symptoms, but by a mean of only about half of one day at day 3 (the time of maximal effect), and by about eight hours overall.

Cochrane Database Syst Rev . 2000;(2):CD000115.
Intrapartum antibiotics for group B streptococcal colonisation; Smaill F; BACKGROUND: Group B streptococcal infection is common in pregnant women without causing harm . However it is also a significant cause of neonatal morbidity and mortality . OBJECTIVES: The objective of this review was to assess the effects of intrapartum administration of antibiotics to women on infant colonization with group B streptococcus, early onset neonatal group B streptococcus sepsis and neonatal death from infection . SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched . SELECTION CRITERIA: Controlled trials of pregnant women colonized with group B streptococcus comparing intrapartum antibiotic administration with no treatment, and providing data on infant colonization with group B streptococcus and/or neonatal infection . DATA COLLECTION AND ANALYSIS: Eligibility and trial quality assessment were done by one reviewer . MAIN RESULTS: Five trials were included . Overall quality was poor, with potential selection bias in all the identified studies . Intrapartum antibiotic treatment reduced the rate of infant colonization (odds ratio 0.10, 95% confidence interval 0.07 to 0.14) and early onset neonatal infection with group B streptococcus (odds ratio 0.17, 95% confidence interval 0.07 to 0 . 39) . A difference in neonatal mortality was not seen (odds ratio 0 . 12, 95% confidence interval 0.01 to 2.00) . REVIEWER'S CONCLUSIONS: Intrapartum antibiotic treatment of women colonized with group B streptococcus appears to reduce neonatal infection . Effective strategies to detect maternal colonization with group B streptococcus and better data on maternal risk factors for neonatal group B streptococcus infection in different populations are required.

Carbohydr Res, 2000 Apr 20, 325(3), 192 - 201
Full assignment of the proton and carbon NMR spectra and revised structure for the capsular polysaccharide from Streptococcus pneumoniae type 17F; Jones C et al.; Full proton, 13C and 31P NMR assignments for the capsular polysaccharide from Streptococcus pneumoniae Type 17F are reported, and a revised structure differing in the anomeric configuration of the sidechain beta-Galp residue proposed . This polysaccharide is a component of the current 23-valent polysaccharide vaccine . The implications of this revised structure for published work are discussed.

Braz J Infect Dis, 2000 Apr, 4(2), 61 - 6
Oral levofloxacin in the treatment of community-acquired pneumonia; Nicodemo AC et al.; We evaluated the efficacy of oral levofloxacin (500mg/day for 7-21 days) in the treatment of 20 adults patients with community-acquired pneumonia (CAP) requiring hospitalization in an open prospective study . The microbiological cause of the pneumonia was identified in 14/20 patients using lower respiratory tract secretions obtained by bronchoscopy (12) and/or blood culture (2) . Eight patients had S . pneumoniae, 2 P.aeruginosa, 1 H.influenzae, 1 S.aureus, 1 mixed S . aureus and K.pneumoniae, and 1 E.coli and Grp.D Streptococcus . All of the patients evaluated were judged to be improved or cured . Levofloxacin is an additional option as monotherapy for the treatment of CAP.

Arch Dis Child Fetal Neonatal Ed, 2000 May, 82(3), F205 - 7
Neonatal group B streptococcal infection in South Bedfordshire, 1993-1998; Beardsall K et al.; BACKGROUND: Group B streptococcus (GBS) is now the leading cause of neonatal bacterial sepsis in the western world . The incidence of GBS infection in the United States has been determined, and guidelines produced and implemented for the prevention of neonatal infection . Neither incidence nor guidelines are currently established in the United Kingdom . AIM: To define the pattern of neonatal infection within one hospital (Luton and Dunstable Hospital) . METHOD: A six year retrospective analysis was performed . RESULT: An incidence of early onset GBS of 1.15 per 1000 deliveries, comparable with that documented in the United States, was found.

Am Fam Physician, 2000 Apr 15, 61(8), 2410 - 6
Acute otitis media: part II . Treatment in an era of increasing antibiotic resistance; Pichichero ME; Antibiotic resistance is increasing among the pathogens that commonly cause acute otitis media . This development may merit changes in the traditional antibiotic treatment of acute otitis media . Risk factors for resistant pathogens include recent antibiotic treatment of acute otitis media, children in day care facilities, wintertime infections and acute otitis media in children less than two years of age . Amoxicillin remains the antibiotic of first choice, although a higher dosage (80 mg per kg per day) may be indicated to ensure eradication of resistant Streptococcus pneumoniae . Oral cefuroxime or amoxicillin-clavulanate and intramuscular ceftriaxone are suggested second-line choices for treatment failure . Compliance with antibiotic regimens is enhanced by selecting agents that require less frequent dosing (such as one or two times a day) and by prescribing shorter (five days or less) treatment courses . Selective use of tympanocentesis if the patient does not respond to empiric therapy can help confirm the diagnosis and guide effective therapy.

Top Magn Reson Imaging, 2000 Apr, 11(2), 76 - 86
Otogenic intracranial inflammations: role of magnetic resonance imaging; Dobben GD et al.; The clinical course of acute otitis media is usually short, and the process terminates because of the host's immune system, the infection-resistant properties of the mucosal linings, and the susceptibility of the major organisms (beta-hemolytic streptococcus or pneumococcus) to penicillin . However, a small proportion (1% to 5%) of untreated or inadequately treated patients may experience complications . Prior to the development of an intracranial complication of otomastoiditis, warning symptoms or signs may be evident; these include severe earache, severe headache, vertigo, chills and fever, and meningeal symptoms and signs . Increasing headache, particularly temporoparietal headache near the affected ear, often indicates an impending intracranial complication . This symptom, often the only indication of an epidural abscess, demands prompt investigation and medical and surgical intervention . In our experience, computed tomography (CT) permits accurate diagnosis of acute coalescent or latent (masked) mastoiditis and its associated complications . However, magnetic resonance imaging (MRI) remains the study of choice to evaluate otogenic intracranial complications . This article demonstrates the important role of MRI in diagnosing various stages of acute otomastoiditis and its associated complications.

Arch Pediatr, 2000 Apr, 7(4), 391 - 5
{Mycoplasma pneumoniae pneumonia in a four-year-old child with transient abscess in the right lower lobe}; Siret D et al.; The frequency of Mycoplasma pneumoniae infection among community-acquired pneumonia, underestimated for a long time, is now better known . Severe evolution is yet uncommon . Differential diagnosis with Streptococcus pneumoniae is often difficult . CASE REPORT: A 4-year-old child was admitted for a right lower lobe pneumonia, with very high values of white blood cell count and CRP, worsening despite a treatment with high doses of amoxicillin, then with cefotaxime and vancomycin . Diagnosis of M . pneumoniae infection was considered only on the tenth day after admission and confirmed on the thirteenth day . Clinical outcome rapidly improved with macrolide antibiotherapy . Radiologic outcome consisted, two months after the beginning of the pneumonia, in abscess of the right lower lobe, which recovered in one month with continuing oral antibiotherapy . CONCLUSION: Lung abscess is very rare in M . pneumoniae pneumonia, as only two other cases were described in the literature . In all three cases, macrolide therapy was delayed . Those cases highlight the importance of considering M . pneumoniae infection in a beta-lactams-resistant community-acquired pneumonia, whatever its severity may be, and to start macrolide antibiotherapy . Our case also shows the possibility of a conservative treatment in case of pulmonary abscess, if clinical tolerance is good.

East Mediterr Health J, 1999 May, 5(3), 556 - 9
Sinusitis as a cause of orbital cellulitis; Haddadin A et al.; To determine the importance of sinusitis as a cause of orbital cellulitis, the causative organisms and peak age of occurrence, 25 patients hospitalized with orbital cellulitis (ages 8 months to 17 years; 80%, 1-4 years) were studied . Complete blood counts were carried out and radiographic sinus examinations and eye swabs (for culturing) performed prior to antibiotic treatment . Sinusitis was evident in 72% of the patients . Eye swab cultures indicated 80% had streptococcal, staphylococcal or enterococcal infection . The data indicate that sinusitis is an important cause of orbital cellulitis . The most common causative organisms were Streptococcus viridans (44%) and Staphylococcus aureus (32%) . Initial antibiotics should therefore cover both organisms.

Mol Microbiol, 2000 Apr, 36(2), 366 - 76
Extracellular targeting of choline-binding proteins in Streptococcus pneumoniae by a zinc metalloprotease; Novak R et al.; A genetic-based search for surface proteins of Streptococcus pneumoniae involved in adhesion identified a putative zinc metalloprotease (ZmpB) . ZmpB shared high amino acid sequence similarities with IgA1 proteases of Gram-positive bacteria, but ZmpB had neither IgA1 nor IgA2 protease activity . Analysis of a family of surface-expressed proteins, the choline-binding proteins (Cbp's), in a zmpB-deficient mutant demonstrated a global loss of surface expression of CbpA, CbpE, CbpF and CbpJ . CbpA was detected within the cytoplasm . The zmpB-deficient mutant also failed to lyse with penicillin, a sign of lack of function of the Cbp LytA . Immunodetection studies revealed that the autolysin (LytA), normally located on the cell wall, was trapped in the cytoplasm colocalized with DNA and the transformation protein CinA . Trafficking of CinA and RecA to the cell membrane during genetic competence was also not observed in the zmpB-deficient mutant . These results suggest a protease dependent regulatory mechanism governing the translocation of CinA and the Cbp's LytA and CbpA of S . pneumoniae.

J Appl Microbiol, 2000 May, 88(5), 887 - 96
Effect of steroidal saponin from Yucca schidigera extract on ruminal microbes; Wang Y et al.; The effects of steroidal saponins (SAP) isolated from Yucca schidigera extract on ruminal bacteria and fungi were investigated in pure culture studies . Prevotella bryantii, Ruminobacter amylophilus, Selenomonas ruminantium and Streptococcus bovis were cultured through ten 24-h transfers in ruminal fluid medium containing 0 or 25 microg SAP ml-1 (measured as smilagenin equivalents) . The four strains, each non-exposed or pre-exposed to SAP, were then inoculated into medium containing 0 or 250 microgram smilagenin equivalents ml-1 and 24-h growth curves were determined . The cellulolytic ruminal bacteria Ruminococcus flavefaciens, Fibrobacter succinogenes and Rc . albus were cultured for 72 h on Whatman no . 1 filter paper in medium containing 0, 9, 90 or 180 microgram SAP ml-1 for the determination of filter paper digestion and endoglucanase activity . The ruminal bacteria differed in their responses to SAP . Steroidal saponins in the medium reduced the growth of Strep . bovis (P < 0.01 at 2, 3, 4, 5, 6 and 8 h), P . bryantii (P < 0.05 at 4, 5, 6, 8, 10 and 24 h) and Rb . amylophilus (P < 0.05 at 14 and 24 h), but the growth of S . ruminantium was enhanced (P < 0.05) at 10, 14 and 24 h . The growth curves of all four non-cellulolytic species were similar (P > 0.05) between pre-exposed and non-exposed cultures and the concentrations of total SAP and soluble (deglycosylated) SAP in the liquid fraction were unchanged (P > 0.05) over time . Steroidal saponins inhibited the digestion of filter paper by all three cellulolytic bacteria, but F . succinogenes was less (P < 0.05) sensitive to SAP and more (P < 0 . 05) effective at deglycosylating SAP than were Rc . flavefaciens or Rc . albus . Transmission electron microscopy revealed that SAP altered the cell walls of the SAP-inhibited non-cellulolytic bacteria . The ruminal fungi, Neocallimastix frontalis and Piromyces rhizinflata, were cultured on filter paper in medium containing 0, 0 . 45, 2.25 or 4.5 microgram SAP ml-1 . Filter paper digestion by both fungi was completely inhibited by 2.25 microgram SAP ml-1 . Steroidal saponins from Y . schidigera inhibit cellulolytic ruminal bacteria and fungi, but their effects on amylolytic bacteria are species dependent and similar to the effects of ionophores . As such, SAP may be useful in nutritional applications targeting starch-digesting ruminal micro-organisms.

J Appl Microbiol, 2000 Apr, 88(4), 555 - 62
Role of F1F0-ATPase in the growth of streptococcus mutans GS5; Suzuki T et al.; The role of F1F0-ATPase in Streptococcus mutans GS5 was investigated by isolating a mutant (NTS1) defective in enzyme activity by homologous recombination with a plasmid encoding the 5' terminal fragment of the F1F0-ATPase beta-subunit gene . The ATPase activity of NTS1 membranes was 49% that of GS5 membranes . The lag phase of the growth curve of NTS1 was longer than that for GS5, and the lag phase of GS5 and NTS1 were prolonged by the addition of ionophore gramicidin D; at stationary phase, the turbidity of the NTS1 culture was less than that of the GS5 culture . These results suggest that S . mutans F1F0-ATPase contributes to the generation of a stoichiometric electrogenic gradient effectively in the lag phase.

J Clin Microbiol, 2000 May, 38(5), 1731 - 4
Use of clindamycin disks To detect macrolide resistance mediated by ermB and mefE in Streptococcus pneumoniae isolates from adults and children; Waites K et al.; We studied 198 macrolide-resistant S . pneumoniae isolates obtained from adults and children to evaluate whether 2-microgram clindamycin disks can distinguish between isolates manifesting ermB- versus mefE-mediated resistance to clarithromycin and to determine the relative frequency with which each resistance mechanism occurred in these populations . The mefE gene was predominant among 109 isolates from children, occurring in 73.4% versus 50.6% of 89 isolates from adults . Three isolates (1.5%) did not amplify either gene . Among 125 mefE(+) isolates, the MIC of clarithromycin at which 90% of the isolates tested were inhibited, determined by Etest, was 32 microgram/ml versus >256 microgram/ml in 70 ermB(+) isolates . All ermB(+) isolates were highly resistant to clindamycin (MICs >256 microgram/ml), whereas all mefE(+) isolates were susceptible to clindamycin using the 2-microgram disk . Testing S . pneumoniae from the respiratory tract for susceptibility to clindamycin by agar disk diffusion is an easy and inexpensive method to estimate the frequency of resistance mediated by ermB in specific patient populations . Macrolide resistance mediated by ermB is usually of greater magnitude than that due to mefE . Clinical studies are needed to determine the significance of high- versus low-level macrolide resistance in S . pneumoniae.

Perfusion, 2000 Mar, 15(2), 161 - 8
Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study; Stammers AH et al.; Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms . The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction . A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus . On admission, he was in respiratory arrest suffering from profound acidemia . In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC) . The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10% . Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml) . In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33 . Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32 . Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy . The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day . The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.

J Chemother, 2000 Apr, 12(2), 134 - 7
Penicillin-resistant and -intermediate Streptococcus pneumoniae in Saudi Arabia; Shibl AM et al.; The antibiotic susceptibility was analyzed of approximately 400 consecutive isolates of S . pneumoniae isolated from different regions of Saudi Arabia . Most of these isolates were from respiratory (sputum, otitis, 53.8%), blood/CSF (26.3%) and ophthalmic (20%) specimens . Overall 6.2% of the isolates were penicillin-resistant (MICs > or =2 microg/ml) and 51.2% were -intermediate (MICs 0.1-1 microg/ml) . The resistance rates to cefuroxime, clarithromycin and ceftriaxone were 14.9%, 14.8% and 4.5% respectively . Only 3.5% of S . pneumoniae showed resistance to amoxycillin/clavulanic acid . The MICs of all tested antibiotics increased as did the penicillin MICs . Penicillin resistance was significantly associated with resistance to cefuroxime (p<0.001) but not with the others . These data indicate the presence of penicillin and multiple-resistant pneumococci in Saudi Arabia and that these strains can spread among individuals . A greater awareness with extended indications for microbiological diagnosis, antimicrobial susceptibility testing and restrictive prescription of antibiotics are needed.

J Chemother, 2000 Apr, 12(2), 129 - 33
Effects of subinhibitory concentrations of moxifloxacin in an in-vitro dynamic model; Maggiolo F et al.; The postantibiotic effect (PAE), sub-MIC effect (SME) and postantibiotic sub-MIC effect (PASME) of moxifloxacin were investigated in an in-vitro dynamic model reproducing in-vivo elimination kinetics of the antibiotic . The PAE was induced by exposing strains of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae to 5 x MIC of the antibiotic for 1.5 hours . After induction, cultures were washed to eliminate the antibiotic and resuspended into the dynamic model either in the presence or absence of a subinhibitory concentration of the antibacterial agent of 0.5 x MIC . Unexposed controls were treated similarly . PASMEs were constantly longer than corresponding SMEs, but differences between them were not statistically significant . Both PASMEs (mean 11:17 hours, range from 8:17 to 14:57) and SMEs (mean 9:23 hours, range from 6:03 to 12:34) had an initial bactericidal effect and were significantly longer than PAEs (mean 1:31 hours, range from 0:21 to 2:14) . The primary effect of moxifloxacin sub-MICs appears to be prevalent in PAE . The possibility of once-daily dosing of the drug is strengthened.

J Chemother, 2000 Apr, 12(2), 124 - 8
Short-term bactericidal activity of amoxicillin and cefotaxime against penicillin-susceptible and -resistant pneumococcal strains: an in vitro pharmacodynamic simulation; Fenoll A et al.; The 8-hour in vitro activity of serum-simulated concentrations of amoxicillin (obtained after 875 mg oral dose) and cefotaxime (obtained after a 1 g i.v . dose), against 20 strains of the 5 Streptococcus pneumoniae serotypes most prevalent in Spain, was explored . Despite a greater initial inocula decrease observed with cefotaxime against the resistant strains at the first sampling time, a decrease > or =99.9% was obtained with both beta-lactams from 6h onwards against the penicillin-susceptible strains; the same was observed for the penicillin-resistant strains with amoxicillin but not with cefotaxime.

Arch Environ Contam Toxicol, 2000 May, 38(4), 540 - 5
Sensitivity of a standard host resistance assay using Streptococcus agalactiae for assessing exposure to immunotoxicants in wild cotton rats (Sigmodon hispidus); Jones LC et al.; Resident small mammals have been used for in situ biomonitoring of contaminated waste sites containing suspected immunotoxicants . Host resistance assays, which involve challenging animals with an actual pathogen, allow for testing of overall immune system function in animals . Because such assays have not been evaluated for use with wild rodent species, it was our objective to assess the efficacy of Streptococcus agalactiae as a pathogenic model for use in a host resistance assay for detecting alterations in immune system function in wild cotton rats (Sigmodon hispidus) . The ability of the assay to detect immunosuppression was evaluated by inducing immunosuppression chemically (cyclophosphamide or dexamethasone) and by protein malnutrition . The estimated lethal dose of S . agalactiae that killed 50% of challenged animals (LD50) was 5.76x10(7) colony-forming units (CFUs) . Although bacterial agglutination titers indicated that animals developed an antibody response when immunized, immunization was not sufficient to adequately protect animals from a subsequent pathogenic challenge . Sensitivity of the host resistance assay was only suitable for detecting substantial immunosuppression, such as that induced by protein malnutrition or dexamethasone administration.

West Indian Med J, 2000 Mar, 49(1), 61 - 4
A retrospective analysis of invasive Streptococcus pneumoniae infections in Trinidad; Williams KP et al.; A retrospective analysis of culture-positive cases of S pneumoniae from normally sterile body fluids is reported . Over 40% of patients were 5 years old or less while 28% of patients were 50 years old or more . Meningitis (44%) was the commonest clinical presentation followed closely by pneumonia (31%) . The commonest predisposing disorder was human immunodeficiency virus infection though there were no identifiable risk factors in the majority of patients . Mortality from invasive pneumococcal disease was significantly higher in elderly patients compared with other age groups (p = 0.0003) . In this study, all S pneumoniae isolates, for which there were antibiotic sensitivity data, were penicillin and/or amoxycillin sensitive.

J Oral Rehabil, 2000 Mar, 27(3), 269 - 70
Streptococcus mutans in saliva of normal subjects and neck and head irradiated cancer subjects after consumption of honey; Sela M et al.; The antibacterial activity of natural honey consumption has been examined in patients suffering from head and neck cancer who developed hyposalivation following irradiation treatment . Enumeration of total bacteria and streptococcus mutans was carried out in saliva of the patients and of a normal volunteer group before and after honey consumption . Total bacteria count was not significantly different between both groups, whereas the streptococcus mutans count decreased significantly in the experimental group following honey consumption.

Plasmid, 2000 May, 43(3), 205 - 13
Construction of a tightly regulated plasmid vector for Streptococcus pneumoniae: controlled expression of the green fluorescent protein; Nieto C et al.; We have constructed a regulated plasmid vector for Streptococcus pneumoniae, based on the streptococcal broad-host-range replicon pLS1 . As a reporter gene, we subcloned the gfp gene from Aequorea victoria, encoding the green fluorescent protein . This gene was placed under the control of the inducible P(M) promoter of the S . pneumoniae malMP operon which, in turn, is regulated by the product of the pneumococcal malR gene . Binding of MalR protein to the P(M) promoter is inactivated by growing the cells in maltose-containing media . Highly regulated gene expression was achieved by cloning in the same plasmid the P(M)-gfp cassette and the malR gene, thus providing the MalR regulator in cis . Pneumococcal cells harboring this vector gave a linear response of GFP synthesis in a maltose-dependent mode without detectable background levels in the absence of the inducer .

Pediatr Infect Dis J, 2000 Apr, 19(4), 394 - 7
Efficacy of pneumococcal conjugate vaccines in large scale field trials; Shinefield HR et al.; BACKGROUND: Each year Streptococcus pneumoniae causes approximately 1.2 million deaths worldwide from pneumonia . In the United States S . pneumoniae is estimated to cause 500,000 cases of pneumonia and 7 million episodes of acute otitis media annually . CONJUGATE VACCINES: The current pneumococcal polysaccharide vaccine is ineffective in children <2 years old and may not produce an adequate antibody response until children reach the age of 5 years . Pneumococcal conjugate vaccines are immunogenic after primary and booster vaccination in young children and in children and adults with immunodeficiencies . Immunization with conjugate vaccines also induces a strong and rapid anamnestic response and enhanced functional activity of antibodies . Two large scale field trials of pneumococcal conjugate vaccines were initiated in 1995, 1 in California and 1 in Finland . The California trial, involving 37,868 children, evaluated the efficacy of a 7-valent conjugate for the prevention of invasive pneumococcal disease and secondarily evaluated its efficacy for acute otitis media and pneumonia . RESULTS: Preliminary results indicate 94% efficacy against invasive pneumococcal disease caused by serotypes included in the vaccine in fully or partially vaccinated children . Preliminary evidence from large scale field trials indicates that pneumococcal conjugate vaccines are effective in reducing invasive pneumococcal disease as well as acute otitis media and pneumonia in children and represents a significant advance in the prevention of childhood infectious diseases.

Pediatr Infect Dis J, 2000 Apr, 19(4), 388 - 93
Immunogenicity of pneumococcal conjugate vaccines; Eskola J; BACKGROUND: Prevention of pneumococcal infections is a public health priority because of the high impact of the disease and because of the increasing problems due to antimicrobial resistance . Traditional vaccines, consisting of purified capsular polysaccharides (PSs) of Streptococcus pneumoniae, are not immunogenic in young children . In addition they confer only limited protection in patients with immunodeficiencies and hematologic malignancies . IMMUNOGENICITY OF PNEUMOCOCCAL CONJUGATE VACCINES: Immunogenicity of the PS vaccine has been enhanced by coupling pneumococcal PSs to proteins to produce a conjugate vaccine . Conjugate molecules are designed to possess T cell dependent properties, such as immunogenicity in early infancy, stimulation of high levels of IgG isotype antibodies and enhanced immunologic memory responses . In the clinical studies multivalent pneumococcal conjugate vaccines have been shown to induce an IgG-dominating serum antibody response against common pneumococcal serotypes causing infections in children . A booster dose later in life creates a robust and rapid antibody response, indicating the existence of immunologic memory in primed children . Antibodies induced by conjugate vaccines are functionally active, as demonstrated by their high avidity and opsonophagocytic activity.

Pediatr Infect Dis J, 2000 Apr, 19(4), 373 - 7
Etiology and treatment of pneumonia; McCracken GH Jr; BACKGROUND: Lower respiratory tract infections are a common cause of morbidity among children . Among these infections pneumonia is the most serious illness and can be difficult to diagnose . The etiology of pneumonia is still partly unknown, primarily because of difficulty in obtaining adequate samples and lack of reliable diagnostic methods . ETIOLOGY OF PNEUMONIA: Streptococcus pneumoniae is recognized as an important cause of pediatric pneumonia regardless of age in both the inpatient and outpatient setting . In developed countries S . pneumoniae probably accounts for 25 to 30% of cases of pediatric community-acquired pneumonia . Viruses (mostly respiratory syncytial virus) are responsible for approximately 20% of cases, and Chlamydia pneumoniae and Mycoplasma pneumoniae occur commonly in older children . FUTURE CHALLENGES: Despite the effectiveness of antimicrobial therapy, the emergence of resistant bacterial pathogens has resulted in increased interest in developing more effective vaccines . If conjugate pneumococcal vaccines prove effective at eradicating carriage of pneumococci in the nasopharynx, immunization may be an important tool against the spread of pneumococcal disease . Future challenges include implementation of effective intervention strategies, production of simple diagnostic tools and development of effective vaccines.

Pediatr Infect Dis J, 2000 Apr, 19(4), 312 - 8
Bacteremia in febrile Malawian children: clinical and microbiologic features; Walsh AL et al.; BACKGROUND: There are no published data for the incidence or etiology of childhood bacteremia in Malawi . We describe the clinical and microbiologic features of children admitted to hospital from whom blood cultures yielded bacterial pathogens . METHODS: Any neonate or child admitted to the pediatric wards of the Queen Elizabeth Central Hospital had a blood culture taken in the event of fever without obvious clinical explanation . Clinical and microbiologic data were prospectively collected for children with a significant positive culture . RESULTS: Between September, 1996, and August, 1997, we processed 2,123 cultures . Of these, 365 (17.2%) grew a pathogen . Non-typhi salmonellae (NTS) and enteric Gram-negative bacilli constituted 67.4% of isolates, and Streptococcus pneumoniae constituted 16.4% . More than two-thirds of NTS episodes coincided with the peak malaria transmission season (January to June); 67% of bacteremic children were malnourished, 28% severely so . Patients with NTS bacteremia were significantly more likely to have coincident malaria and to have splenomegaly and anemia than children with other infecting organisms . The overall mortality was 38% but varied considerably according to age and nutritional status . Prior antibiotic use, coincident malaria or meningitis did not adversely affect outcome . In vitro resistance to the commonly available antibiotics ampicillin and trimethoprim-sulfamethoxazole was found in 76 and 71% of NTS isolates . Screening tests for penicillin resistance suggested a rate of 21% among pneumococci . CONCLUSIONS: Bacteremia is common in hospitalized Malawian children and has a high mortality . There are high rates of resistance to some of the commonly used antibacterial agents.

Pediatr Infect Dis J, 2000 Apr, 19(4), 298 - 303
Predictive value of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children; Eldan M et al.; BACKGROUND: Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics . Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM . Nasopharyngeal colonization with S . pneumoniae was found to increase significantly during episodes of AOM . OBJECTIVES: To investigate the nasopharyngeal colonization with S . pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM . MATERIALS AND METHODS: Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied . Simultaneous nasopharyngeal cultures for S . pneumoniae and middle ear fluid cultures were obtained at enrollment . Antibiotic susceptibility testing was performed in all S . pneumoniae isolates . Penicillin and ceftriaxone MICs for S . pneumoniae were determined by E-test . The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S . pneumoniae in middle ear fluid were calculated . RESULTS: We studied 362 and 217 children with NT-AOM and NR-AOM, respectively . Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age . S . pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively . Penicillin-nonsusceptible S . pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs . 47%; P < 0.01) . Antibiotic susceptibility patterns were similar for S . pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM . A positive nasopharyngeal culture had only little predictive value for the presence of S . pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively) . However, the negative predictive value of nasopharyngeal cultures for recovery of S . pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs . 78%, respectively; P = 0.009) . The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S . pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively . Conclusions . A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S . pneumoniae was found in patients with NR-AOM than in those with NT-AOM . Negative nasopharyngeal culture for antibiotic-resistant S . pneumoniae practically rules out its presence in middle ear fluid.

Pediatr Infect Dis J, 2000 Apr, 19(4), 293 - 8
Etiology of community-acquired pneumonia in 254 hospitalized children; Juven T et al.; BACKGROUND: Childhood community-acquired pneumonia is a common illness, but there have been relatively few comprehensive studies of the viral and bacterial etiology in developed countries . The aim of the present investigation was to determine the etiology of community-acquired pneumonia in hospitalized children by several laboratory methods . METHODS: In a 3-year prospective study a nasopharyngeal aspirate for viral studies and acute and convalescent serum samples for viral and bacterial serology were taken from 254 children with symptoms of acute infection and infiltrates compatible with pneumonia in the chest radiograph . The role of 17 microbes was investigated . RESULTS: A potential causative agent was detected in 215 (85%) of the 254 patients . Sixty-two percent of the patients had viral infection, 53% had bacterial infection and 30% had evidence of concomitant viral-bacterial infection . Streptococcus pneumoniae (37%), respiratory syncytial virus (29%) and rhinovirus (24%) were the most common agents associated with community-acquired pneumonia . Only one patient had a positive blood culture (S . pneumoniae) of 125 cultured . A dual viral infection was detected in 35 patients, and a dual bacterial infection was detected in 19 patients . CONCLUSIONS: The possible causative agent of childhood community-acquired pneumonia can be detected in most cases . Further studies are warranted to determine what etiologic investigations would aid in the management of pneumonia . With effective immunization for S . pneumoniae and respiratory syncytial virus infections, more than one-half of the pneumonia cases in this study could have been prevented.

Curr Opin Pulm Med, 2000 May, 6(3), 226 - 33
Community-acquired pneumonia; Gant V et al.; Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide and has significant financial implications for health-care systems . The epidemiology and fundamental biology of the disease has evolved, reflecting the human immunodeficiency virus pandemic, increasing world travel, and, as always, poverty . The promise held out by molecular diagnostic technology has yet to deliver in this arena, and antibiotic resistance continues to drive the quest for new antimicrobial agents . The emergence of multidrug-resistant Streptococcus pneumoniae, the microorganism most often implicated as a cause of CAP, continues to threaten treatment options . The evolution of this organism, the persistently high mortality rate associated with CAP, and increasing health-care costs have prompted the publication of guidelines by various authorities that can be used to assist in the initial assessment of the patient and then guide empirical antimicrobial therapy . It is unclear whether these guidelines will have significant impact on cost and mortality, although the trend toward a rational and evidence-based approach to antimicrobial therapy must be a goal to aspire to.

Infection, 2000 Mar-Apr, 28(2), 114 - 5
Streptococcus pneumoniae peritonitis postpartum; Kahlke V et al.; A peritonitis caused by an ascending infection is a rare complication postpartum . A 37-year-old woman presented with a secondary peritonitis due to Streptococcus pneumoniae . The patient had given birth to a healthy boy 4 weeks before and showed no symptoms of a bronchitis on admission . An operation was performed after the patient developed an acute abdomen, showing a diffuse peritonitis . High vaginal swabs and blood cultures taken on admission were positive for S . pneumoniae as well as the specimen taken during the operation . Thus we concluded that this was a case of an ascending infection . After antibiotic therapy with penicillin the patient could be discharged 8 days after the operation.

Infection, 2000 Mar-Apr, 28(2), 68 - 73
Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis; Hedlund J et al.; BACKGROUND: The diagnostic value of admission serum levels of procalcitonin (PCT) and C-reactive protein (CRP) as indicators of the etiology and prognosis was prospectively investigated . PATIENTS: 96 patients, 50-85 years of age, treated in the hospital for community-acquired pneumonia (CAP) . RESULTS: On admission, all patients had elevated CRP levels (> 10 mg/l), but only 60 patients (54%) had elevated PCT levels (> 0.1 microgram/l) . The severity of disease measured by APACHE II score was strongly associated with admission levels of PCT (p = 0.006), but not with CRP . Eight of nine patients with pneumonia caused by atypical agents had PCT levels < 0.5 microgram/l compared with 6/27 patients with pneumonia caused by classic bacterial pathogens, mainly Streptococcus pneumoniae (p = 0.03) . No such correlation between CRP levels and etiology was found . CONCLUSION: Our data indicate that in patients admitted to the hospital with CAP, measurement of PCT gives information about the severity of the disease, and may aid the physician to differentiate typical bacterial etiology from atypical etiology, and thereby to choose appropriate initial antibiotic treatment.

Vet Microbiol, 2000 May 11, 73(4), 319 - 25
Identification of virulence associated markers in the cell wall of pigeon Streptococcus gallolyticus strains; Vanrobaeys M et al.; The cell wall protein profiles of 56 isolates of Streptococcus gallolyticus of differing virulence for pigeons were compared by SDS-PAGE . Additionally, Western blot analysis was performed on the cell wall proteins of 14 strains using sera of pigeons, experimentally infected with A(+)T1 or A(-)T2 strains of S . gallolyticus . The profile of silver stained gels exhibited a complex array of 20-50 bands ranging from less than 6.5-210kDa . A band with molecular mass of 114kDa was only observed in isolates that belonged to the highly virulent A(+)T1, A(+)T2, A(+)T3 and A(-)T1 culture supernatant groups . A band with a slightly higher molecular mass (115kDa) as well as a 207kDa band were only detected in isolates that belonged to the moderately A(-)T3 or low A(-)T2 virulent culture supernatant groups . The 114 and 115kDa band were recognised by all homologous and heterologous pigeon sera used whereas the 207kDa band was only recognised by sera of pigeons infected with a A(-)T2 strain . These findings may indicate that the 114, 115 and 207kDa bands are useful as additional virulence associated markers for pigeon S . gallolyticus strains.

Biophys J, 2000 May, 78(5), 2668 - 74
Direct probing by atomic force microscopy of the cell surface softness of a fibrillated and nonfibrillated oral streptococcal strain; van Der Mei HC et al.; In this paper, direct measurement by atomic force microscopy (AFM) of the cell surface softness of a fibrillated oral streptococcal strain Streptococcus salivarius HB and of a nonfibrillated strain S . salivarius HBC12 is presented, and the data interpretation is validated by comparison with results from independent techniques . Upon approach of the fibrillated strain in water, the AFM tip experienced a long-range repulsion force, starting at approximately 100 nm, attributed to the compression of the soft layer of fibrils present at the cell surface . In 0.1 M KCl, repulsion was only experienced when the tip was closer than approximately 10 nm, reflecting a stiffer cell surface due to collapse of the fibrillar mass . Force-distance curves indicated that the nonfibrillated strain, probed both in water and in 0.1 M KCl, was much stiffer than the fibrillated strain in water, and a repulsion force was experienced by the tip at close approach only (20 nm in water and 10 nm in 0.1 M KCl) . Differences in cell surface softness were further supported by differences in cell surface morphology, the fibrillated strain imaged in water being the only specimen that showed characteristic topographical features attributable to fibrils . These results are in excellent agreement with previous indirect measurements of cell surface softness by dynamic light scattering and particulate microelectrophoresis and demonstrate the potential of AFM to directly probe the softness of microbial cell surfaces.

J Clin Gastroenterol, 2000 Apr, 30(3), 332 - 5
Primary peritonitis due to group A streptococcus; Moskovitz M et al.; Primary peritonitis is a rare condition occurring, by definition, in patients without underlying causes, such as perforated viscus, pre-existing ascites, or nephrosis . We report a case of primary peritonitis and shock due to group A beta-hemolytic streptococcus, a rare etiology . A review of the world's literature shows a predilection for women to have this condition . The entry site is obscure in most cases . Asymptomatic genital tract colonization may be a portal of entry in some women . Shock or toxic shock syndrome often accompany the abdominal findings . Laparotomy to exclude a perforated viscus may be unavoidable . Despite the significant morbidity, expeditious and appropriate antibiotic therapy is curative.

Vaccine, 2000 May 22, 18(23), 2541 - 8
Immunization with Streptococcus bovis protects against lactic acidosis in sheep; Gill HS et al.; Lactic acidosis is a gastrointestinal disorder resulting from the rapid overgrowth of lactic acid-producing bacteria when ruminants are suddenly introduced to grain feed . The present study has investigated the ability of live and killed bacterial vaccines to reduce lactic acidosis in sheep, via a stimulation of specific antibody production against lactic acid-producing bacteria . Forage-fed sheep were immunized with live or killed Streptococcus bovis Sb-5 vaccine, with or without adjuvant, via intramuscular injection . After the primary immunization, three boosters were given at 2-4 week intervals . Sheep were subsequently challenged by a sudden switch to a grain-based diet . Following challenge, vaccinated sheep maintained significantly higher feed intake, and had higher rumen pH, lower L-lactate concentrations, and less severe diarrhoea scores than non-vaccinated control sheep . Higher rumen pH, lower mortality and less severe diarrhoea were found in the animals immunized with live vaccine compared to the animals immunized with killed vaccines . Significant increases in mucosal and systemic antibody responses were observed after boosting; the S . bovis-specific antibody concentrations were significantly higher in samples of saliva, rumen fluid and serum from sheep immunized with live vaccine than with killed vaccines . These results demonstrate that lactic acidosis can be reduced by immunization against S . bovis, and that live Sb-5 vaccine is effective in invoking mucosal as well as systemic antibody responses.

Vet J, 2000 May, 159(3), 262 - 9
Immunization with a Streptococcus bovis vaccine administered by different routes against lactic acidosis in sheep; Shu Q et al.; Streptococcus bovis is an important lactic acid bacterium in the rumen, which contributes to the development of lactic acidosis . This study was designed to test the efficacy of immunization with S . bovis primed either intramuscularly (i.m.) or intraperitoneally (i.p . ) against lactic acidosis . Forty-five wethers were allocated to three treatment groups . Two groups were injected with a S . bovis vaccine by either the i.m . or i.p . route for primary immunization; both groups were further immunized by the same route(s) (oral and/or i.m.) for boosters . The third group was not immunized (control) . Antibody concentrations were measured in saliva prior to and following animals being fed a grain diet, and also in the rumen fluid, before the animals were suddenly introduced to a grain diet . The average antibody concentration in the animals of the i.m . group was higher than the i.p . group (P< 0.05) . The antibody concentration in the rumen fluid of immunized sheep was higher than the control animals (P< 0.01) . The difference in the rumen fluid antibody concentration between the i.m . and i.p . groups was not statistically significant (P> 0.05) . In the i.m . group, there was a significantly greater feed intake, higher rumen pH, lower diarrhoea scores, and less increase in blood packed cell volume following grain feeding than in the animals of the control group . The severity of diarrhoea and the increase of blood packed cell volume in the animals of the i . p . group were also less than in the animals of the control group . The results suggest that the risk of lactic acidosis can be reduced by immunization against S . bovis, and that the immunization primed i . m . is more effective than the immunization primed i.p .

Shock, 2000, 13(4), 297 - 306
Synergistic septicemic action of the gram-positive bacterial cell wall components peptidoglycan and lipoteichoic acid in the pig in vivo; Middelveld RJ et al.; Despite the fact that gram-positive infections constitute around 50% of all cases leading to septic shock, little is yet known about the mechanisms involved . This study was carried out to find out more about the effects of cell wall components peptidoglycan (PepG) and lipoteichoic acid (LTA) of the gram-positive bacterium Streptococcus pyogenes in the pig . Specific pathogen-free pigs (20 kg bodyweight) were pretreated with metyrapone (a cortisol-synthesis inhibitor) and then were given 2-h infusions of 160 microg/kg of PepG (n = 5), 160 microg/kg LTA (n=5), or a combination of both (LTA + PepG, 160 microg/kg each, n = 5) . Four hours after start of the infusions, the PepG, LTA, and LTA + PepG groups showed decreases in mean arterial pressure (change of -11%, -25%, and -47% from baseline, respectively), dynamic lung compliance (-18%, -24%, and -38%), arterial oxygen tension (-10%, -16%, and -37%), changes in blood leukocyte numbers (+11%, -27%, and -67%), and increases in pulmonary vascular resistance index (+7%, +106%, and +307% from baseline) and metabolic acidosis (base excess values decreased with 1.8, 2.3 and 8.1 units) . The differences between the PepG and LTA + PepG groups were statistically significant (P < 0.05, Kruskal-Wallis tests), but not between LTA and LTA + PepG groups . However, no changes in systemic nitric oxide (NO) production could be detected, which is much in contrast to studies on lower order animals . Moreover, comparison of the results obtained using this model with those obtained in a model of endotoxin-induced septic shock showed distinct difference in the mechanisms by which gram-positive and gram-negative bacterial components exert their actions . For example, a marked fall in systemic blood pressure and dynamic lung compliance is seen in both models, but in the present gram-positive sepsis model, much less interleukin-8 and tumor necrosis factor-alpha are produced . In conclusion, this study showed that PepG and LTA act synergistically to cause respiratory failure and septic shock in the pig . The infusion of the combination of PepG and LTA in the pig could serve as a new, well-controlled model for studies of gram-positive sepsis.

Annu Rev Med, 2000, 51, 271 - 88
Streptococcal toxic shock syndrome associated with necrotizing fasciitis; Stevens DL; Streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis is a rapidly progressive process that kills 30-60% of patients in 72-96 h . Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations . Thus, the challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures . Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T-cell proliferation and watershed production of monokines (e.g . tumor necrosis factor alpha, interleukin 1, interleukin 6), and lymphokines (e.g . tumor necrosis factor beta, interleukin 2, and gamma-interferon) . Penicillin, though efficacious in mild Streptococcus pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary-phase organisms . Emerging treatments for strep TSS include clindamycin and intravenous gamma-globulin.

Schweiz Med Wochenschr, 2000 Mar 18, 130(11), 395 - 7
Unusual association: Streptococcus bovis tricuspid endocarditis with atrial-septal aneurysm and patent foramen ovale; Sommer R et al.; Streptococcus bovis endocarditis is a frequent cause of streptococcal endocarditis and is associated with colonic tumours . The tricuspid valve is very rarely affected and its involvement is a complication which can lead to a less favourable outcome . We report the seventh case of tricuspid valve endocarditis due to S . bovis, and the first, to our knowledge, to be associated with an atrial-septal aneurysm and a patent foramen ovale . The underlying medical conditions and predisposing factors for development of tricuspid valve endocarditis are described and interesting new echocardiographic data are presented . The current guidelines on antibiotic therapy for S . bovis tricuspid valve endocarditis are reviewed.

Caries Res, 2000 Mar-Apr, 34(2), 194 - 200
The effect of chronic clonidine administration on salivary glands and caries in the rat; Watson GE et al.; Clonidine is a widely prescribed, centrally acting antihypertensive with proposed pharmacologic mechanisms of stimulation of central postsynaptic alpha(2)-adrenergic receptors and agonist activity at presynaptic alpha(2)-adrenergic receptors, interfering with peripheral regulation of norepinephrine and acetylcholine release . Both of these mechanisms are capable of adversely influencing salivary output and composition, potentially leaving an individual with increased caries risk . The purpose of the present study was to determine the effect of chronic administration of clonidine on saliva, salivary glands, and caries in rats . Sprague-Dawley rat pups were infected with Streptococcus sobrinus, given Diet 2000 and 10% sucrose water ad libitum, and either desalivated, or treated with clonidine HCl (125 or 250 microg/kg administered daily for 28 days by means of osmotic minipumps), or assigned as controls . There were no statistical differences in stimulated parotid or submandibular gland salivary output or sublingual gland weights among the groups . The weight of the submandibular glands as a percent of total body weight was significantly decreased in animals that received clonidine when compared with controls . Sulcal caries scores in both clonidine groups and smooth surface caries scores in the high clonidine group were increased when compared with control animals . Positive control animals (desalivated) had significantly higher caries scores than all other groups . These data show that chronic administration of clonidine significantly decreases submandibular gland weight and increases susceptibility to dental caries.

N Z Med J, 2000 Feb 25, 113(1104), 58 - 62
Outpatient treatment of pneumonia; Grant CC et al.; In children, pneumonia must be differentiated from bronchiolitis and asthma . Pneumonia is the only one of these three conditions for which antibiotics are indicated . Clinical signs are more useful than radiological or laboratory investigations for differentiating pneumonia from bronchiolitis and asthma . A child has pneumonia if s/he has tachypnoea or indrawing and is not wheezing . The child's age and the severity of the illness episode predict the aetiology of the pneumonia . The majority of children with community-acquired pneumonia can be managed in primary care . The antibiotic of choice for children < or = 5 years of age is oral amoxycillin and for older children and adolescents is oral erythromycin . Antibiotics will not prevent pneumonia in a child with an upper respiratory tract infection . Up to 80% of adults with pneumonia can be managed as outpatients . Indicators of morbidity and mortality from pneumonia are well described . Clinical features and radiology do not reliably predict the causative agent in adults with pneumonia, thus initial treatment is empirical . Streptococcus pneumoniae is the most common cause of pneumonia in all studies . The initial antibiotic treatment should be active against this organism . Penicillin oramoxycillin or erythromycin are all suitable . Erythromycin has the advantage of being active against Mycoplasma pneumoniae and Legionella species . Follow-up of patients is important to decide whether they are responding to the empirical treatment.

Intern Med, 2000 Mar, 39(3), 266 - 9
Toxic shock-like syndrome caused by T serotype B3264 streptococcus; Saeki A et al.; A 45-year-old woman was transferred from a local hospital to our hospital because of shock-like manifestations in addition to septic polyarthritis and necrotizing cellulitis of the left leg . Since Streptococcus pyogenes was isolated from the blood culture examined one day before admission, the diagnosis of streptococcal toxic shock-like syndrome (TSLS) was made . Antibiotic treatment together with supportive care started at the time of admission, resulting in clinical improvement, although poststreptococcal acute glomerulonephritis occurred during the period . TSLS is a life-threatening disease, but early recognition of the disease and prompt initiation of appropriate treatment may lead to successful outcome.

Am J Vet Res, 2000 Apr, 61(4), 446 - 9
Use of specific sugars to inhibit bacterial adherence to equine endometrium in vitro; King SS et al.; OBJECTIVE: To determine whether specific sugars inhibit adhesion of Streptococcus zooepidemicus, Pseudomonas aeruginosa, and Escherichia coli to equine endometrial epithelial cells in vitro . SAMPLE POPULATION: Endometrial biopsy specimens collected during estrus from 7 healthy mares . PROCEDURE: Endometrial specimens on glass slides were incubated for 30 minutes at 4 C with suspensions of S . zooepidemicus, P . aeruginosa, or E . coli in phosphate-buffered saline solution (PBSS) alone or with various concentrations of D-(+)-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-(+)-glucose, galactose, or N-acetyl-neuraminic acid . Inhibition of bacterial adherence was determined by comparing adhesion of bacteria (i.e., percentage of glandular epithelial cells with adherent bacteria) suspended in each sugar solution with that of bacteria suspended in PBSS . RESULTS: Mannose and N-acetyl-D-galactosamine inhibited adhesion of E . coli and P . aeruginosa to epithelial cells, whereas only mannose inhibited adhesion of S . zooepidemicus . The other sugars did not affect bacterial adherence . CONCLUSIONS AND CLINICAL RELEVANCE: Mannose and N-acetyl-D-galactosamine appear to play a role in adhesion of S . zooepidemicus, P . aeruginosa, and E . coli to equine endometrium . In horses with uterine infections, use of sugars to competitively displace bacteria from attachment sites on cells may provide an adjunct to antibiotic treatment.

Clin Infect Dis, 2000 Apr, 30 Suppl 1, S5 - 14
Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy; Kaplan JE et al.; The incidence of nearly all AIDS-defining opportunistic infections (OIs) decreased significantly in the United States during 1992-1998; decreases in the most common OIs (Pneumocystis carinii pneumonia inverted question markPCP, esophageal candidiasis, and disseminated Mycobacterium avium complex inverted question markMAC disease) were more pronounced in 1996-1998, during which time highly active antiretroviral therapy (HAART) was introduced into medical care . Those OIs that continue to occur do so at low CD4+ T lymphocyte counts, and persons whose CD4+ counts have increased in response to HAART are at low risk for OIs, a circumstance that suggests a high degree of immune reconstitution associated with HAART . PCP, the most common serious OI, continues to occur primarily in persons not previously receiving medical care . The most profound effect on survival of patients with AIDS is conferred by HAART, but specific OI prevention measures (prophylaxis against PCP and MAC and vaccination against Streptococcus pneumoniae) are associated with a survival benefit, even when they coincide with the administration of HAART . Continued monitoring of incidence trends and detection of new syndromes associated with HAART are important priorities in the HAART era.

Antimicrob Agents Chemother, 2000 May, 44(5), 1352 - 5
Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid; Trampuz A et al.; The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin . In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied . SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation.

Antimicrob Agents Chemother, 2000 May, 44(5), 1291 - 5
Pharmacodynamic assessment of cefprozil against Streptococcus pneumoniae: implications for breakpoint determinations; Nicolau DP et al.; Cefprozil, an oral semisynthetic cephalosporin, is commonly utilized in the treatment of respiratory-tract infections in children . While this agent has provided acceptable clinical success over a number of years, this study was undertaken to better define its pharmacodynamic profile against Streptococcus pneumoniae . Nineteen clinical isolates of S . pneumoniae were utilized in the neutropenic murine thigh infection model . To simulate the pharmacokinetic profile of cefprozil in children, the renal function of mice was impaired with uranyl nitrate, and a commercially available cefprozil suspension (6 mg/kg of body weight) was administered orally every 12 h . Mice were infected with 10(6) to 10(7) CFU per thigh, and therapy was initiated 2 h later . At 0 and 24 h postinfection, thighs were harvested to determine bacterial density . Survival was assessed during 96 h of therapy . The magnitude of bacterial kill ranged from 0.5 to 4.4 log(10) CFU per thigh over 24 h, and the extent of microbial eradication was dependent on the MIC . Killing of more than 2.6 log(10) CFU per thigh was observed with MICs of < or =3 microg/ml, while either minimal killing or growth was detected with MICs of > or =4 microg/ml . Mortality in untreated control animals was 100% . Animals infected with strains for which the MICs were < or =2 microg/ml survived the infection, whereas MICs exceeding 2 microg/ml resulted in substantial mortality . These studies demonstrate the effectiveness of cefprozil against isolates of the pneumococcus for which the MICs are < or =2 microg/ml using a drug exposure typically observed in children . These data support a susceptibility breakpoint of < or =2 microg/ml for cefprozil.

Antimicrob Agents Chemother, 2000 May, 44(5), 1247 - 54
Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection; Knudsen JD et al.; The emergence of resistance to various antibiotics in pneumococci leaves the glycopeptides as the only antibiotics against which pneumococci have no resistance mechanism . This situation has led to a renewed interest in the use of glycopeptides . It has not yet been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment with glycopeptides in animal models or in humans . We used the mouse peritonitis model with immunocompetent mice and with Staphylococcus aureus and Streptococcus pneumoniae as infective organisms . A wide spectrum of different treatment regimens with vancomycin and teicoplanin was tested to study the pharmacodynamics of these drugs . In studies in which the single dose that protected 50% of lethally infected mice (ED(50)) was given as one dose or was divided into two doses, survival was significantly decreased when the dose was divided . The only statistically significant correlations between the percentage of survival of the mice after 6 days and each of the PK/PD parameters were for peak concentration (C(max))/MIC and S . aureus and for the free fraction of C(max) (C(max-free))/MIC and S . pneumoniae . For S . pneumoniae, the ED(50) for different dosing regimens increased with the number of doses given; e.g., the single-dose ED(50)s for vancomycin and teicoplanin were 0.65 and 0 . 45 mg/kg, respectively, but the ED(50)s for dosing regimens with 2-h doses given for 48 h were 6.79 and 5.67 mg/kg, respectively . In experiments with 39 different vancomycin dosing regimens and 40 different teicoplanin dosing regimens against S . pneumoniae, the different PK/PD parameters were analyzed using logistic regression . The C(max-free)/MIC was one of two parameters that best explained the effect for both drugs; for vancomycin, the other important parameter was the AUC/MIC, and for teicoplanin, the other parameter was the time the free fraction of the drug is above the MIC . The effect analyzed as a function of C(max-free)/MIC disclosed thresholds with shifts from almost no effect to full effect at ratios of five to six for vancomycin and two to three for teicoplanin.

J Pak Med Assoc, 2000 Feb, 50(2), 58 - 60
Antibiotic susceptibility of Streptococcus pneumoniae in Karachi; Rehman N et al.; OBJECTIVE: To evaluate, record and analyse the comparative activity of a range of oral antibiotics against Streptococcus pneumoniae . SETTING: Specimen collected at a private laboratory and some received from different hospitals and clinics . MATERIALS: The specimen comprised of Sputum, Throat Swabs, C.S.F., Pus, Pleural fluid, Ear Swabs, Eye Swabs, Bronchial Wash, Prostatic discharge and Antral Secretions . METHODS: The isolates were tested for their antibiotic susceptibility using the E-test by the methods described in the study protocol . The groups of antibiotics tested were Amoxicillin--Clavulanate, Clarithromycin, Cefaclor, Cefuroxime, Ceftriaxone and Penicillin . RESULTS: A total of 116 strains of Streptococcus pneumoniae were isolated and susceptibility to Amoxicillin-Clavulanate was 100%, 99.1% strains were susceptible to Cefuroxime and 0.9% were intermediate . Susceptibility to Penicillin was 80.2% and 19.8% of the strains were in intermediate category, while susceptibility to Clarithromycin was 89.7%, 1.7% were in intermediate region and 8.6% of the strains were resistant to this antibiotic . The susceptibility pattern of Cefaclor was not calculated as there is no current NCCLS--97 Cefaclor breakpoints available . CONCLUSION: The percentage of drug resistant Streptococcus pneumoniae was negligible in Karachi during the study period, however it is important to monitor the susceptibility pattern to keep a check on an increase in the number of DRSP as reported at different centres in Turkey, Saudi Arabia, Singapore, Thailand, Hong Kong and Indonesia.

Biochem J, 2000 May 1, 347 Pt 3, 633 - 41
Large-scale synthesis and functional elements for the antimicrobial activity of defensins; Raj PA et al.; Human neutrophil defensins, and their analogues incorporating anionic, hydrophobic or cationic residues at the N- and C-termini, were synthesized by solid-phase procedures . The synthetic defensins were examined for their microbicidal activity against Candida albicans, two Gram-negative bacteria (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) and two Gram-positive bacteria (Streptococcus gordonii and Streptococcus mutans) . The human neutrophil peptide 1 (HNP1) and HNP2 were found to be potent candidacidal agents . HNP3, which differs by one amino acid at the N-terminus of its sequence, was totally inactive . The Gram-negative bacteria A . actinomycetemcomitans and P . gingivalis and the Gram-positive bacteria S . gordonii and S . mutans were insensitive to human defensins . However, the insertion of two basic residues, such as arginine, at both the N-terminus and the C-terminus of HNP2 significantly enhanced antifungal and antibacterial activity . The addition of anionic residues, such as aspartic acid, at the N- and C-termini rendered the molecule totally inactive . The presence of two hydrophobic amino acids, such as valine, at the N-terminus of HNP2 and of two basic arginine residues at its C-terminus resulted in molecules that were optimally active against these oral pathogens . The results suggest that the N- and C-terminal residues in defensin peptides are the crucial functional elements that determine their microbicidal potency . The three-dimensional structure of all defensins constitutes the same amphiphilic beta-sheet structure, with the polar face formed by the N- and C-terminal residues playing an important role in defining microbicidal potency and the antimicrobial spectrum . The enhanced microbicidal activity observed for defensin peptides with two basic residues at both the N- and C-termini could be due to optimization of the amphiphilicity of the structure, which could facilitate specific interactions with the microbial membranes.

Lancet, 2000 Apr 8, 355(9211), 1225 - 30
Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya; Scott JA et al.; BACKGROUND: Despite a substantial disease burden, there is little descriptive epidemiology of acute pneumonia in sub-Saharan Africa . We did this study to define the aetiology of acute pneumonia, to estimate mortality at convalescence, and to analyse mortality risk-factors . METHODS: We studied 281 Kenyan adults who presented to two public hospitals (one urban and one rural) with acute radiologically confirmed pneumonia during 1994-96 . We did blood and lung-aspirate cultures, mycobacterial cultures, serotype-specific pneumococcal antigen detection, and serology for viral and atypical agents . FINDINGS: Aetiology was defined in 182 (65%) patients . Streptococcus pneumoniae was the most common causative agent, being found in 129 (46%) cases; Mycobacterium tuberculosis was found in 26 (9%) . Of 255 patients followed up for at least 3 weeks, 25 (10%) died at a median age of 33 years . In multivariate analyses, risk or protective factors for mortality were age (odds ratio 1.51 per decade {95% CI 1.04-2.19}), unemployment (4.42 {1.21-16.1}), visiting a traditional healer (5.26 {1.67-16.5}), visiting a pharmacy (0.30 {0.10-0.91}), heart rate (1.64 per 10 beats {1.24-2.16}), and herpes labialis (15.4 {2.22-107}) . HIV-1 seropositivity, found in 52%, was not associated with mortality . Death or failure to recover after 3 weeks was more common in patients with pneumococci of intermediate resistance to benzylpenicillin, which comprised 28% of pneumococcal isolates, than in those infected with susceptible pneumococci (5.60 {1.33-23.6}) . INTERPRETATION: We suggest that tuberculosis is a sufficiently common cause of acute pneumonia in Kenyan adults to justify routine sputum culture, and that treatment with benzylpenicillin remains appropriate for clinical failure due to M . tuberculosis, intermediate-resistant pneumococci, and other bacterial pathogens . However, interventions restricted to hospital management will fail to decrease mortality associated with socioeconomic, educational, and behavioural factors.

Infect Immun, 2000 May, 68(5), 3028 - 33
Immunization of mice with combinations of pneumococcal virulence proteins elicits enhanced protection against challenge with Streptococcus pneumoniae; Ogunniyi AD et al.; The vaccine potential of a combination of three pneumococcal virulence proteins was evaluated in an active-immunization-intraperitoneal-challenge model in BALB/c mice, using very high challenge doses of Streptococcus pneumoniae . The proteins evaluated were a genetic toxoid derivative of pneumolysin (PdB), pneumococcal surface protein A (PspA), and a 37-kDa metal-binding lipoprotein referred to as PsaA . Mice immunized with individual proteins or combinations thereof were challenged with high doses of virulent type 2 or type 4 pneumococci . The median survival times for mice immunized with combinations of proteins, particularly PdB and PspA, were significantly longer than those for mice immunized with any of the antigens alone . A similar effect was seen in a passive protection model . Thus, combinations of pneumococcal proteins may provide the best non-serotype-dependent protection against S . pneumoniae.

Infect Immun, 2000 May, 68(5), 2819 - 26
Role of manganese-containing superoxide dismutase in oxidative stress and virulence of Streptococcus pneumoniae; Yesilkaya H et al.; Streptococcus pneumoniae was shown to contain two types of superoxide dismutase, MnSOD and FeSOD . Levels of MnSOD increased during growth in an aerobic environment . The sodA gene, encoding MnSOD, of virulent S . pneumoniae type 2 strain D39 was inactivated to give mutant D39HY1 . Aerobically, D39HY1 had a lower growth rate than the wild type and exhibited susceptibility to the redox-active compound paraquat, but anaerobic growth of D39HY1 was identical to that of the wild type . Virulence studies showed that the median survival time of mice infected intranasally with D39HY1 was significantly longer than that of mice infected with the wild-type pneumococcus . In contrast to the wild type, D39HY1 did not multiply in lungs during the first 24 h but thereafter grew at the same rate as the wild type . Appearance in the bloodstream was also delayed, but growth in the blood was unimpaired by the sodA mutation . The pattern of inflammation in lungs infected with D39HY1 differed from that in wild-type-infected mice . After infection with D39HY1, neutrophils were densely packed around bronchioles, in contrast to the wild-type infection, where neutrophils were more diffusely localized.

Infect Immun, 2000 May, 68(5), 2621 - 9
Characterization of recombinant, ureolytic Streptococcus mutans demonstrates an inverse relationship between dental plaque ureolytic capacity and cariogenicity; Clancy KA et al.; Dental caries results from prolonged plaque acidification that leads to the establishment of a cariogenic microflora and demineralization of the tooth . Urease enzymes of oral bacteria hydrolyze urea to ammonia, which can neutralize plaque acids . To begin to examine the relationship between plaque ureolytic activity and the incidence of dental caries, recombinant, ureolytic strains of Streptococcus mutans were constructed . Specifically, the ureABCEFGD operon from Streptococcus salivarius 57.I was integrated into the S . mutans chromosome in such a way that the operon was transcribed from a weak, cognate promoter in S . mutans ACUS4 or a stronger promoter in S . mutans ACUS6 . Both strains expressed NiCl(2)-dependent urease activity, but the maximal urease levels in ACUS6 were threefold higher than those in ACUS4 . In vitro pH drop experiments demonstrated that the ability of the recombinant S . mutans strains to moderate a decrease in pH during the simultaneous metabolism of glucose and urea increased proportionately with the level of urease activity expressed . Specific-pathogen-free rats that were infected with ACUS6 and fed a cariogenic diet with drinking water containing 25 mM urea and 50 microM NiCl(2) had relatively high levels of oral urease activity, as well as dramatic decreases in the prevalence of smooth-surface caries and the severity of sulcal caries, relative to controls . Urease activity appears to influence plaque biochemistry and metabolism in a manner that reduces cariogenicity, suggesting that recombinant, ureolytic bacteria may be useful to promote dental health.

Hybridoma, 2000 Feb, 19(1), 23 - 31
Selection of an immunogenic and protective epitope of the PsaA protein of Streptococcus pneumoniae using a phage display library; Srivastava N et al.; Streptococcus pneumoniae is an important pathogen that causes disease in young and elderly individuals . The currently available polysaccharide vaccines have limited efficacy in those age groups most susceptible to pneumococcal infections . This study focuses on mapping the epitopes of a surface protein of S . pneumoniae by biopanning a 15 mer phage display library using 5 different monoclonal antibodies (MAbs) against the Pneumoccal surface adhesin A (PsaA) . PsaA is a component of the bacterial cell wall that is highly species specific and is involved in bacterial adherence and virulence . Biopanning of the phage display library reveals three distinct epitopes on the PsaA protein . The sequence homology of these epitopes ranges from two to six amino acids when compared to the native PsaA protein type 2 . Two of these epitopes have been evaluated for their immunogeneicity in mice . The peptide selected by the MAbs 8G12, 6F6, and 1B7 is referred to as the consensus peptide and is immunogenic in mice . Optimal anti-PsaA response is observed in mice immunized with 50microg of the consensus peptide complexed to proteosomes in 1:1 ratio . The anti-PsaA response is significantly lower than the response to the PsaA native protein . The peptide selected by monoclonal antibody 4E9 in its lipidated form is significantly protective in mice challenged with S . pneumoniae serotype 2 when compared to mice immunized with the native protein . These results show that the selected epitopes of PsaA protein are immunogenic and protective in mice . These epitopes need to be evaluated further as alternatives to currently available vaccines.

J Chemother, 2000 Feb, 12(1), 17 - 21
In vitro activity of cefepime and cefotaxime compared to six other agents against 350 penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae; Gomez-Lus R et al.; From January 1996 to December 1997, we evaluated the in vitro activity of 8 antimicrobials (penicillin, amoxycillin, amoxycillin/clavulanate, cefuroxime, ceftazidime, cefepime, cefotaxime, and imipenem) against 350 Streptococcus pneumoniae clinical isolates collected from two hospitals . Imipenem, cefepime and cefotaxime were the most active antibiotics against penicillin-intermediate (PI) and highly penicillin-resistant (PR) S . pneumoniae with MICs 2- to 8-fold lower than penicillin . Against PI and PR pneumococci amoxycillin and amoxycillin/clavulanate were 2-times less active than cefepime and cefotaxime, while cefuroxime was 4-8-times less active . The majority of strains of serotypes 6B, 23F, 14, 9 and 19 were penicillin-resistant, both intermediate (68%) and highly resistant (32%).

Minerva Med, 1999 Oct, 90(10), 369 - 75
{Spontaneous bacterial peritonitis (SBP): prevalence and characteristics in a population of 314 cirrhotic patients evaluated at hospital admission}; Marelli A et al.; BACKGROUND: The aim of this study was to evaluate the incidence and the characteristics of the infections of ascitic fluid in cirrhotic patients at the moment of hospital admission . METHODS: A total of 314 patients consecutively submitted to ascitic fluid tap within 3 days of hospital admission were studied . Each patient was classified according to Child-Plugh classes . Neoplastic ascites were excluded . The ascitic fluid was analyzed for PMN count, protein and albumin content, cultural and cytological examinations . The patients with ascitic fluid PMN > 250/ml were immediately treated with antibiotics . RESULTS: Out of 314 patients 11% had SBP (94% in class C patients according to Child-Plugh classification), 17% CNNA and 3% MNNB . 15% of SBP patients were asymptomatic . Total protein content in ascitic fluid was significantly lower in SBP and MNNB compared to CNNA and sterile ascites . 56% of the isolated bacteria was Gram-negative, and the most frequently found were Streptococcus, Escherichia coli and Staphylococcus . 80% of the patients with ascites infection underwent third generation cephalosporin treatment . SBP mortality (29%) was significantly higher than CNNA (9%), MNNB (10%) and sterile ascites (11%), also taking into account the subgroup without ascites infection and class C group (14%) . CONCLUSIONS: In view of the high incidence (even in the absence of invasive procedures), of the possibility of symptom free patients and of the high mortality of SBP, it is advisable to carry out routine tap in all cirrhotics with ascites at hospital admission.

FEMS Immunol Med Microbiol, 2000 May, 28(1), 55 - 65
Atypical behaviour and survival of Streptococcus pyogenes L forms during intraperitoneal infection in rats; Michailova L et al.; Groups of rats were injected intraperitoneally with cell wall-deficient (L) forms of Streptococcus pyogenes, with their parental (S) forms, as well as with a combined inoculum of both forms (S+L) . Peritoneal exudate samples were harvested on days 1, 3, 7, 15 and 30 after challenge and were investigated by microbiological, electron microscopic, cytometric and biochemical methods . Parental S forms were isolated from peritoneal exudate samples up to day 15 post infection, while L form cultures were isolated until the end of the examined interval . Electron microscopic examination revealed continuous adhesion of L forms on the macrophage surface as well as intracellular persistence inside them . It was demonstrated that the intraperitoneal inflammatory response to L form infection was higher than to the other infections and the monocyte-macrophage populations were predominant . The established atypical behaviour and long survival of S . pyogenes L forms in the rat's peritoneum could explain some of the mechanisms of the pathogens' persistence as well as the reasons for chronic streptococcal infections.

J Dent Res, 2000 Mar, 79(3), 824 - 8
Antibacterial activities and release kinetics of a newly developed recoverable controlled agent-release system; Ehara A et al.; We attempted to develop a resin with a recoverable antibacterial activity based on the desorption/adsorption of a cationic bactericide by the ion-exchange mechanism . The aims of this study were to investigate the release kinetics of the agent and the antibacterial activity of this newly designed resin system . An experimental resin was prepared by the addition of methacrylic acid as a cation-exchanger and a cationic antibacterial agent, cetylpyridinium chloride (CPC), to triethyleneglycol dimethacrylate . The amount of CPC desorbed from the experimental resin into buffer solutions at pH 4-8 was measured . The adsorption of CPC to control resin and re-adsorption of CPC to the experimental resin, which had once desorbed the agent, were also determined . The antibacterial activity of experimental resin against Streptococcus mutans was evaluated, and the relationship between bacterial acid production and antibacterial effect was assessed . The experimental resin desorbed CPC at pH < or = 6, and the amount of agent desorbed increased with increasing acidity . The control resin adsorbed CPC when immersed in CPC aqueous solution at a rate determined by the concentration of the agent and immersion time . The experimental resin, once desorbed CPC, could re-adsorb the bactericide by being exposed to a solution of the agent . Less plaque formed on the experimental resin, and the growth and survival of S . mutans was inhibited in the condition in which acid was produced . These results demonstrate that the resin system proposed was able to desorb and re-adsorb the cationic bactericide by an ion-exchange mechanism and could show an inhibitory effect on S . mutans growth and plaque formation.

Dent Update, 1999 Nov, 26(9), 374 - 80
The caries vaccine: a growing prospect; Ma JK; A vaccine against dental caries, for so long a subject of purely academic research, is currently undergoing phase II clinical trials and could be available commercially within 5 to 6 years . The approach, which is safe, effective, and provides long-term protection for up to a year, is based on a topical application and does not require any injections . The development of this vaccine has been made possible by recent advances in molecular biology and genetic engineering . Perhaps one of the most intriguing aspects has been the use of green plants to produce the vaccine . This article describes a topical vaccine against Streptococcus mutans, which is the main cause of dental caries.

Diagn Microbiol Infect Dis, 2000 Apr, 36(4), 269 - 72
Serious streptococcal infections produced by isolates resistant to streptogramins (quinupristin/dalfopristin): case reports from the SENTRY antimicrobial surveillance program; Kugler KC et al.; The emergence and sustained prevalence of Gram-positive organisms resistant to antimicrobials has been of interest for over a decade . Quinupristin/dalfopristin (formerly RP 59500 or Synercid) is a new injectable streptogramin combination that has been reported to have activity against Gram-positive organisms, even those with documented MLS(B) resistance . However, the two case reports presented here illustrate three well-documented Streptococcus spp . strains (S . mitis, S . pneumoniae) to be resistant to quinupristin/dalfopristin (MICs at 3, 8, and 12 microg/ml) following referral as routine isolates in the SENTRY Antimicrobial Surveillance Program . The S . pneumoniae pleural fluid isolate was cross-resistant to erythromycin . Both bacteremic S . mitis strains were resistant to macrolides (erythromycin, azithromycin, clarithromycin), lincosamides (clindamycin), and fluoroquinolones . Patient histories indicated no prior use of MLS class antimicrobials for the S . mitis case, but the patient having the S . pneumoniae isolate did receive prior treatment of erythromycin and clindamycin . All isolates had modestly increased penicillin MICs of 0.12 microg/ml . The mode of resistance to quinupristin/dalfopristin was not evident (sat A-negative by PCR); and these cases illustrate the existence of streptogramin-resistant isolates before the introduction of this antimicrobial class into human clinical practice.

Diagn Microbiol Infect Dis, 2000 Apr, 36(4), 275 - 8
PCR fingerprinting analysis for differentiation of Streptococcus pneumoniae reinfection versus relapse; Hunt Gerardo S et al.; Polymerase chain reaction fingerprint profiles of isolates obtained during an episode of pneumococcal pneumonia with bacteremia differed significantly from profiles of isolates obtained from the same patient during a subsequent episode of pneumococcal meningitis with bacteremia . Polymerase chain reaction fingerprinting provides a means of differentiating new infection from relapse, and may be a simple molecular tool for comparison of Streptococcus pneumoniae isolates.

J Am Board Fam Pract, 2000 Mar-Apr, 13(2), 107 - 10
Self-collection of antepartum anogenital group B streptococcus cultures; Torok PG et al.; BACKGROUND: Group B streptococcus (GBS) from the maternal perineum is a leading cause of serious neonatal infection . Recommendations by the Centers for Disease Control and Prevention include cultures from anogenital swabs on all pregnant women between 35 and 37 weeks' gestation . This study examines whether a significant difference in test results exists between GBS cultures from swabs done by physicians and those done by patients, and whether patients prefer to perform the swab themselves, with the potential of enhancing patient satisfaction and decreasing utilization of health care resources . METHODS: Study design was a comparison of 250 obstetrics patients attending a military community hospital family medicine clinic . Patients were assigned on an alternating basis to perform an anogenital culture swab before or after the physician performed a swab . Patients were designated to complete a preference survey before or after the swabs were performed . Descriptive statistics, chi square, and McNemar's test corrected for multiple comparisons, and the Kruskal-Wallis test on effect of order on test outcome were used to analyze the data . RESULTS: Forty-two of 250 patients had positive cultures . There was no statistically significant difference between swab results done by patients and those done by physicians . There was no significant difference between results of first swabs and results of second swabs . Of the 250 patients 145 preferred self-collection . There was no statistically significant relation between preference and order of completion of the questionnaire . CONCLUSIONS: Patient-collection technique is as accurate as physician collection . A majority of patients in this study population preferred self-collection of GBS swabs.

Unfallchirurg, 2000 Feb, 103(2), 160 - 3
{Fatal streptococcal infection after tibial intramedullary nailing . Case report}; Schwarz N; A 29 years old patient with an unsuspicious medical history is reported, two developed a toxic shock syndrome after intramedullary nailing for a closed tibia fracture . The patient died within 24 hours . The infection was caused by Streptococcus Group A . The diagnosis of the toxic shock syndrome was not without difficulties and was delayed . Post mortem examination revealed an unknown acute leukemia of the myeloic type.

Clin Cardiol, 2000 Apr, 23(4), 301 - 3
Tricuspid valve group B streptococcal endocarditis after an elective termination of pregnancy; Kangavari S et al.; A patient developed fever, chills, and shortness of breath after an elective first trimester dilation and curettage . Blood cultures grew Group B streptococcus, and a transesophageal echocardiogram revealed a 2 x 2 cm vegetation on the tricuspid valve and global left ventricular hypokinesis . A 6-week course of parenteral antibiotics and vasodilator therapy resulted in resolution of the valvular vegetation as well as of the left ventricular dysfunction.

J Infect Dis, 2000 Apr, 181(4), 1501 - 5 Epub 2000 Apr 13.
Increased carriage of trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae in Malawian children after treatment for malaria with sulfadoxine/pyrimethamine; Feikin DR et al.; Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children . Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study . Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later . Pneumococci were tested for antibiotic susceptibility by broth microdilution . In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P=.048) . For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P=.0017) and returned to 41.7% at the 4-week follow-up . Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.

J Infect Dis, 2000 Apr, 181(4), 1414 - 20 Epub 2000 Apr 13.
A hospital-based prevalence survey of bloodstream infections in febrile patients in Malawi: implications for diagnosis and therapy; Archibald LK et al.; The etiology of bloodstream infections (BSIs) in febrile (> or =37.5 degrees C) adults (> or =18 years old) in one Malawi hospital were determined during August and September 1997 . After clinical evaluation, blood was drawn for comprehensive culture, human immunodeficiency virus (HIV) type 1 testing, and malaria smear . Of 233 patients, 173 (74%) were HIV-1 infected, and 70 (30%) had BSI . BSI pathogens included 25 (33%) Streptococcus pneumoniae and 21 (28%) Mycobacterium tuberculosis . Nine patients (4%) had malaria parasitemia . BSIs were more likely in HIV-1-positive than in -negative patients (62/173 vs . 8/60, P<.01) . Clinical predictors of BSI included HIV-1 infection and altered mental status . Mortality among inpatients with BSI was higher than among those without BSI (P<.001) . In conclusion, S . pneumoniae and M . tuberculosis are frequent causes of BSI in febrile adults . Similar surveys, performed periodically in developing countries, may assist in the identification of clinical predictors of BSI and in planning appropriate therapy.

J Infect Dis, 2000 Apr, 181(4), 1330 - 6 Epub 2000 Apr 13.
A pneumococcal protein that elicits interleukin-8 from pulmonary epithelial cells; Madsen M et al.; To understand how neutrophils are recruited to the lung in pneumococcal pneumonia, the ability of pneumococcal components to elicit the chemokine interleukin (IL)-8 from monolayers of cultured human type II cells was assessed . Heat-killed clinical and laboratory strains of Streptococcus pneumoniae and secreted proteins from exponentially growing pneumococci elicited significant quantities of IL-8 from A549 cells . All strains that elicited IL-8 production secreted a protein ( approximately 90 kDa) that comigrated on SDS-PAGE with a C3-binding protein previously identified in S . pneumoniae . As little as 7 pmol of the purified 90-kDa protein readily elicited levels of IL-8 production equivalent to those obtained with 1 U of IL-1alpha . Supernatant proteins and heat-killed cells of an isogenic mutant that failed to produce the C3-binding protein elicited significantly less IL-8 than did supernatant proteins or heat-killed cells of the parent strain . These results implicate the C3-binding protein of S . pneumoniae in a novel pathway of pulmonary inflammation.

Pediatr Clin North Am, 2000 Apr, 47(2), 269 - 85, v
Pneumococcal vaccine; Rubin LG; Streptococcus pneumoniae or pneumococcus is a major pathogen causing meningitis, pneumonia, other invasive infections, and the common infections acute otitis media and sinusitis . The major virulence factor is the polysaccharide capsule, present as one of approximately 90 serotypes . Anticapsular antibodies protect against infection . In 1977 and 1997, vaccines composed of purified capsular polysaccharide from 14- and 23-capsular types, respectively, were licensed for use in those children 2 years of age or older who are at increased risk for invasive pneumococcal infection . These vaccines have limited immunogenicity in infants and young children . Pneumococcal conjugate vaccines in which capsular polysaccharides from a limited number of serotypes are covalently linked to a protein carrier have recently been developed . In preliminary reports of randomized, double-blind control studies, a heptavalent vaccine administered as a series of infections to normal infants was efficacious in the prevention of invasive infections, episodes of lobar pneumonia, and acute otitis media caused by vaccine serotypes.

Eur J Immunol, 2000 Apr, 30(4), 1214 - 23
Immunogenetic analysis of the immune response to pneumococcal polysaccharide; Baxendale HE et al.; Pneumococcal serotype-specific anti-capsular polysaccharide antibodies protect against invasive pneumococcal disease . Within an individual the diversity of these antibodies is limited . To evaluate the repertoire of antibodies to pneumococcus and determine whether oligoclonality is seen both between serotypes and between individuals, we sampled the B cell repertoire induced by polysaccharide and conjugate vaccine in adult volunteers . Fifteen hybridomas secreting pneumococcus-specific monoclonal antibodies were generated from five volunteers . Ten were isotype switched, six were IgG2 and four were IgA . These included two isotype switch variants of the same clone . V(H)3 and V(kappa)2 were used by 10/15 and 7/13 of the sequenced clones, respectively, with identical genes, V(H)3-48 and V(kappa)2-A17 used by a number of volunteers to a variety of serotypes . VDJ junctional characteristics and complementarity-determining region (CDR) 3 length were variable . High levels of somatic mutation in CDR1 and 2, inconsistent with a primary response, were found in 10/11 of the isotype-switched antibodies, including those induced by plain polysaccharide antigens . These data suggest that wild-type infection or nasopharyngeal carriage of Streptococcus pneumoniae in adults may induce memory and the response to subsequent immunization with plain polysaccharide or conjugate pneumococcal vaccines may have the characteristics of a secondary response.

Mol Microbiol, 2000 Mar, 35(6), 1431 - 42
Tyrosine phosphorylation of CpsD negatively regulates capsular polysaccharide biosynthesis in streptococcus pneumoniae; Morona JK et al.; In Streptococcus pneumoniae, the first four genes of the capsule locus (cpsA to cpsD) are common to most serotypes . By analysis of various in-frame deletion and site-directed mutants, the function of their gene products in capsular polysaccharide (CPS) biosynthesis was investigated . We found that while CpsB, C and D are essential for encapsulation, CpsA is not . CpsC and CpsD have similarity to the amino-terminal and carboxy-terminal regions, respectively, of the autophosphorylating protein-tyrosine kinase Wzc from Escherichia coli . Alignment of CpsD with Wzc and other related proteins identified conserved Walker A and B sequence motifs and a tyrosine rich domain close to the carboxy-terminus . We have shown that CpsD is also an autophosphorylating protein-tyrosine kinase and that point mutations in cpsD affecting either the ATP-binding domain (Walker A motif) or the carboxy-terminal {YGX}4 repeat domain eliminated tyrosine phosphorylation of CpsD . We describe, for the first time, the phenotypic impact of these two mutations on polysaccharide production and show that they affect CPS production differently . Whereas a mutation in the Walker A motif resulted in loss of encapsulation, mutation of the tyrosines in the {YGX}4 repeat domain resulted in an apparent increase in encapsulation and a mucoid phenotype . These data suggest that autophosphorylation of CpsD at tyrosine attenuates its activity and reduces the level of encapsulation . Additionally, we demonstrated that CpsC is required for CpsD tyrosine phosphorylation and that CpsB influences dephosphorylation of CpsD . These results are consistent with CpsD tyrosine phosphorylation acting to negatively regulate CPS production . This has implications for the function of CpsC/CpsD homologues in both Gram-positive and Gram-negative bacteria and provides a mechanism to explain regulation of CPS production during pathogenesis.

Proc Natl Acad Sci U S A, 2000 Apr 25, 97(9), 4891 - 6
Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes; Filipe SR et al.; Penicillin-resistant strains of Streptococcus pneumoniae contain low affinity penicillin-binding proteins and often also produce abnormal indirectly crosslinked cell walls . However the relationship between cell wall abnormality and penicillin resistance has remained obscure . We now show that the genome of S . pneumoniae contains an operon composed of two genes (murM and murN) that encode enzymes involved with the biosynthesis of branched structured cell wall muropeptides . The sequences of murMN were compared in two strains: the penicillin-susceptible strain R36A producing the species-specific pneumococcal cell wall peptidoglycan in which branched stem peptides are rare, and the highly penicillin-resistant transformant strain Pen6, the cell wall of which is enriched for branched-structured stem peptides . The two strains carried different murM alleles: murM of the penicillin-resistant strain Pen6 had a "mosaic" structure encoding a protein that was only 86.5% identical to the product of murM identified in the isogenic penicillin-susceptible strain R36A . Mutants of R36A and Pen6 in which the murMN operon was interrupted by insertion-duplication mutagenesis produced peptidoglycan from which all branched muropeptide components were missing . The insertional mutant of Pen6 carried a pbp2x gene with the same "mosaic" sequence found in Pen6 . On the other hand, inactivation of murMN in strain Pen6 and other resistant strains caused a virtually complete loss of penicillin resistance . Our observations indicate that the capacity to produce branched cell wall precursors plays a critical role in the expression of penicillin resistance in S . pneumoniae.

Int J Syst Evol Microbiol, 2000 Mar, 50 Pt 2, 759 - 65
Streptococcus didelphis sp . nov., a streptococcus with marked catalase activity isolated from opossums (Didelphis virginiana) with suppurative dermatitis and liver fibrosis; Rurangirwa FR et al.; beta-Haemolytic, catalase-positive, Gram-positive cocci that formed chains in broth media but did not react with Lancefield group antisera were isolated from skin lesions, spleen, liver and lungs of nine opossums, including eight from a research colony and one from a wildlife rehabilitation organization . The isolates had vigorous catalase activity that was retained on initial passage on non-blood-containing media, but this activity was lost in subsequent passages . The use of standard phenotypic tests did not lead to satisfactory identification of these organisms beyond the genus level, even if the aberrant catalase reaction was not considered . The 16S rRNA gene sequence of the isolates was most similar (96%) to Streptococcus dysgalactiae, but distinct from that species as 16S rRNA gene similarity of different strains of S . dysgalactiae was > 99% . Characterization of biochemical reactions and cell-wall fatty acid profiles also revealed significant differences between the opossum isolates and all other known Streptococcus spp., thus it is proposed as a new species with the name Streptococcus didelphis, sp . nov . The type strain is ATCC 700828T.

Med Arh, 1999, 53(3 Suppl 2), 39 - 41
{Septic conditions: a syndrome of multiorgan dysfunction}; Heljic S et al.; Using a new concept of terminology for sepsis syndrome, septic shock and multiorgan dysfunction/failure syndrome (MODS/MOSF) as a framework, we have evaluated 21 cases of severe sepsis of new admitted newborns in Neonatology Department of Pediatric clinic of Clinical center University of Sarajevo during last 2 years . We found that the most common etiologic agents were gram negative organisms (Klebsiella pn . and E . coli) and staphylococci . We did not observed any streptococcus group B sepsis despite of high incidence of these infections in developed countries . In 12 (60%) of 21 patients with severe sepsis MODS was developed, involving at least two organ systems, 3 of them also had the other acute insult (emergency surgery and asphyxia) as a possible trigger for MODS . The incidence of specific organ failure was: CNS (58%), respiratory (50%), cardiovascular (41%), the other systems were less involved . The overall mortality rate of patients with sepsis was 28%, whereas the overall mortality rate of MODS/MOSF was 50%.

Bratisl Lek Listy, 1999 Nov, 100(11), 587 - 92
Susceptibility of Streptococcus pneumoniae isolated from the respiratory tract of hospitalized children with respiratory tract infections; Slobodnikova L et al.; The most frequent nasopharyngeal carriers of Streptococcus pneumoniae are young children . Frequent use of antimicrobial therapy in children facilitates the selection of penicillin-resistant strains in this population . These strains, especially if highly resistant, may cause serious therapeutic problems . Aim of the study was to monitor penicillin- and multidrug-resistant S . pneumoniae strains in hospitalized children with respiratory tract infections . Hospitalized children up to five years were examined for S . pneumoniae presence in their upper respiratory tract . Susceptibility to penicillin, erythromycin, trimethoprim/sulfamethoxazole, tetracycline, and chloramphenicol was determined by the disk-diffusion method . The minimal inhibitory concentrations (MIC) of penicillin, erythromycin and trimethoprim/sulfamethoxazole were measured by the E-test . S . pneumoniae strain was isolated from 60 (34.7%) out of 173 microbiologically examined children; 2 different strains were isolated in 9 cases . Nine strains (13.0%) were penicillin resistant with MICs ranging from 1.5 to 8 mg/L, and 17 strains (24.6%) had intermediate susceptibility . Seventeen (24.6%) strains were erythromycin resistant (MIC > or = 1 mg/L) . Eighteen strains (26.1%) were resistant and 7 strains (10.1%) were intermediately susceptible to trimethoprim/sulfamethoxazole . Ten strains (14.5%) were not susceptible to tetracycline, and 11 (15.9%) to chloramphenicol . Non-susceptibility (resistance or intermediate susceptibility) to the tested antimicrobials was more prevalent in penicillin-nonsusceptible strains . The current level of S . pneumoniae resistant to antimicrobial drugs in children with respiratory tract infections in the hospital department monitored in our study do not cause problems in the choice of antibacterial therapy . Penicillins still can remain the drug of choice in cases when typical bacterial causing agents of respiratory tract infections are suspected . (Tab . 3, Fig . 2, Ref . 31.)

Clin Ter, 1999 Nov-Dec, 150(6), 449 - 52
{Primary pneumococcal peritonitis: description of a case and review of the literature}; Coialbu T et al.; Streptococcus pneumoniae causes lobar pneumonitis but primary peritonitis can occur in cyrrotic adults as well as in children affected by nephrosis and immunopathies . In young females peritonitis can be the consequence of infection localized at genital organs . Pneumococcal sepsis is becoming rare with the antibiotic era but resistance to penicillin is actually frequent and is becoming a problem for elderly . We report a case of a young woman affected by spontaneous primary peritonitis and pneumococcal sepsis . The prevalent symptoms were gastrointestinal: diarrhea and emesis . No infectious foci could be detected on imaging studies and during surgery.

Emerg Infect Dis, 2000 Mar-Apr, 6(2), 180 - 3
Erythromycin resistance in Streptococcus pyogenes in Italy; Bassetti M et al.; In a prospective study of acute pharyngitis in Italian children, 69 (38.3%) of 180 isolates of Streptococcus pyogenes were resistant to macrolides . S . pyogenes was eradicated in 12 (63.1%) of 19 patients with erythromycin-resistant S . pyogenes treated with clarithromycin and in 22 (88%) of 25 patients with erythromycin-susceptible strains . The constitutive-resistant phenotype was correlated with failure of macrolide treatment.

Emerg Infect Dis, 2000 Mar-Apr, 6(2), 175 - 9
Outbreak among drug users caused by a clonal strain of group A streptococcus; Bohlen LM et al.; We describe an outbreak among drug users of severe soft-tissue infections caused by a clonal strain of group A streptococcus of M-type 25 . Cases (n = 19) in drug users were defined as infections (mainly needle abscesses) due to the outbreak strain . Comparison with controls showed that infected drug users bought drugs more often at a specific place . Drug purchase and use habits may have contributed to this outbreak.

J Infect Dis, 2000 Apr, 181(4), 1322 - 9 Epub 2000 Apr 07.
Acute otitis media caused by antibiotic-resistant Streptococcus pneumoniae in southern Israel: implication for immunizing with conjugate vaccines; Dagan R et al.; The potential coverage of antibiotic-resistant pneumococci causing acute otitis media (AOM) by 7-, 9-, and 11-valent conjugate pneumococcal vaccines was studied in southern Israel . A total of 876 cases of pneumococcal AOM were studied in the context of various clinical conditions . Of the isolates, 68% were resistant to >/=1 drug, 61% were resistant to penicillin, and 13% were resistant to >/=3 antibiotic classes . Antibiotic resistance and coverage by the various candidates were age and population dependent and were higher among those with a complicated clinical course, as indicated by recent antibiotic use and recurrence of AOM . The results suggest that, if efficacious, the conjugate pneumococcal vaccines can substantially reduce the occurrence of pneumococcal AOM in general and complicated pneumococcal AOM in particular.

Carcinogenesis, 2000 Apr, 21(4), 753 - 6
Promotion of intestinal carcinogenesis by Streptococcus bovis; Ellmerich S et al.; The involvement of Streptococcus bovis, an member of the human gut flora, in colorectal neoplastic diseases is an object of controversy . The aim of this study was to determine the effects of S.bovis and of antigens extracted from the bacterial cell wall on early preneoplastic changes in the intestinal tract . Adult rats received i . p . injections of azoxymethane (15 mg/kg body weight) once per week for 2 weeks . Fifteen days (week 4) after the last injection of the carcinogen, the rats received, by gavage twice per week during 5 weeks, either S.bovis (10(10) bacteria) or wall-extracted antigens (100 microg) . One week after the last gavage (week 10), we found that administration of either S.bovis or of antigens from this bacterium promoted the progression of preneoplastic lesions through the increased formation of hyperproliferative aberrant colonic crypts, enhanced the expression of proliferation markers and increased the production of IL-8 in the colonic mucosa . Our study suggests that S.bovis acts as a promoter of early preneoplastic lesions in the colon of rats . The fact that bacterial wall proteins are more potent inducers of neoplastic transformation than the intact bacteria may have important implications in colon cancer prevention.

Neurology, 2000 Apr 11, 54(7), 1433 - 41
Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins; Jorens PG et al.; OBJECTIVE: After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination . BACKGROUND: ADEM is a demyelinating disorder of the CNS sharing many similarities with MS . Demyelination in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens . METHODS: Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; and TCR repertorium analysis by PCR-ELISA and cytokine production . RESULTS: 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S . pyogenes exotoxins . 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation . MBP-reactive T cells showed crossreactivity to S . pyogenes supernatant and exotoxins . 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile . CONCLUSION: In vivo exposure to S . pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.

Pediatr Infect Dis J, 2000 Mar, 19(3), 212 - 5
Acute mastoiditis in children: an increase in frequency in Northern Virginia; Bahadori RS et al.; BACKGROUND: Acute mastoiditis is reported to occur 2 or 3 times annually in the largest children's hospitals . We encountered an average of 1 case annually at our hospital from 1986 to 1991 . During an 8-year period ending October 31, 1999, 22 patients were diagnosed and treated at our hospital . Of these, 17 presented during the last 34 months . METHODS: Retrospective chart review from office and hospital records of children from infancy to age 12 years with a discharge diagnosis of acute mastoiditis who were treated from 1992 through 1999 . RESULTS: All children were referred to one of the two pediatric otolaryngologists in our community because of forward protrusion of the auricle and retroauricular cellulitis . Eleven (50%) were <14 months old . Ninety-five percent had a concomitant ipsilateral, inflamed, bulging, immobile eardrum . Computerized tomographic imaging, performed on all patients, revealed universal cortical destruction, subperiosteal abscess or bone destruction in four and dural venous thrombosis in two . Mastoidectomy was necessary for eight children (36%) because of complications of mastoiditis (n = 4) or for failure to improve with antibiotics and myringotomy drainage (n = 4) . Streptococcus pneumoniae or Streptococcus pyogenes was recovered from 10 of 17 children (59%) from whom cultures were obtained . CONCLUSION: Cases of acute mastoiditis have markedly increased in our suburban children's hospital . The disease was most common during infancy . Serious complications of mastoiditis occurred in four (18%) of the children in this series.

Pediatr Infect Dis J, 2000 Mar, 19(3), 196 - 200
Antimicrobial resistance of Streptococcus pneumoniae isolated from healthy children in day-care centers: results of a multicenter study in Russia; Stratchounski LS et al.; BACKGROUND: It has been previously shown that study of susceptibility of nasopharyngeal isolates in healthy carriers can predict resistance in clinical isolates . The purpose of this multicenter study was to determine the carriage rate of Streptococcus pneumoniae in healthy children attending day-care centers in Moscow, Smolensk and Yartsevo, Russia, and in vitro activity of penicillin G, amoxicillin/clavulanate, cefaclor, erythromycin, roxithromycin, clarithromycin and trimethoprim-sulfamethoxazole (TMP-SMX) against representative isolates . METHODS: Included in this study were 305 pneumococcal isolates from 733 children attending 9 day-care centers in Moscow, Smolensk and Yartsevo . All children enrolled in this study were <7 years of age . MICs of selected antimicrobials were determined by Etest . Serotyping of selected pneumococcal isolates was done with pool and type antisera . RESULTS: The carriage rate of S . pneumoniae in the 3 centers varied from 44.9% to 66.0% (mean, 55.9%) . Susceptibility testing was performed with 305 (74.4%) of 410 isolates . Only 23 (7.5%) of 305 pneumococcal isolates were penicillin-intermediate (range, 2.8 to 12.8%) with no penicillin-resistant strains . All tested pneumococci were susceptible to amoxicillin/clavulanate . Macrolides possessed comparable activity against S . pneumoniae, at 4.6% resistant strains for both erythromycin (range, 1.1 to 17.1%) and clarithromycin (range, 1.7 to 17.1%) . The highest level of resistance was observed with TMP-SMX, 53.4% (range, 43.8 to 70.9%) . Of 23 strains 20 (87.0%) with intermediate resistance to penicillin were serotyped . The most prevalent serotype was 14 (5 isolates), followed by serogroups 19 (4) and 23 (4) . CONCLUSIONS: Resistance to penicillin, other beta-lactams and macrolides does not seem to be a problem for Russia now . The high level of resistance to TMP-SMX considerably restricts its usage for the treatment of pneumococcal infections.

J Zoo Wildl Med, 1999 Dec, 30(4), 587 - 8
Vegetative endocarditis in a scimitar-horned oryx (Oryx dammah); Chai N; Streptococcus uberis was cultured from vegetative endocarditis lesions in a scimitar-horned oryx (Oryx dammah) from the Parc de la Haute Touche, France . This is the first reported single isolation of S . uberis from an oryx with vegetative endocarditis leading to fatal congestive heart failure.

Allergy Asthma Proc, 2000 Jan-Feb, 21(1), 33 - 8
Community-acquired pneumonia: an approach to antimicrobial therapy; Lange M; Community-acquired pneumonia (CAP), the sixth leading cause of death in the United States, has undergone significant changes in the past 30 years . In addition to the fact that it increasingly is a disease affecting the elderly and those patients with underlying comorbidities, the spectrum of microbiological agents causing pneumonia has greatly expanded and includes in addition to Streptococcus pneumoniae many other agents including Mycoplasma, Chlamydia, and respiratory viruses . A major problem encountered by the clinician facing a patient with CAP derives from the imprecise clinical presentation, which in most instances does not permit a precise diagnosis of the etiological agent . As pneumonia, if untreated, is frequently a rapidly progressive illness, the clinician usually chooses antimicrobial agents on an empirical basis . Careful attention to historical, physical, and laboratory findings, as well as age and presence of comorbidities has led to a categorization of CAP into four groupings that assist in deciding whether the patient should be hospitalized and what empirical antimicrobial regimen should be started . Careful follow-up and familiarity with the clinical pneumonic syndromes associated with different microbial agents is essential to assure a successful outcome.

J Laryngol Otol, 1999 Aug, 113(8), 759 - 61
Necrotizing fasciitis after peritonsillar abscess in an immunocompetent patient; Skitarelic N et al.; Cervical necrotizing fasciitis (CNF) is a rapidly progressive, severe bacterial infection of the fascial planes of the head and neck . Group A beta haemolytic Streptococcus spp . (GABHS), Staphylococcus spp., or obligatory anaerobic bacteria are the most common causative pathogens . The disease usually results from a dental source or facial trauma . Extensive fascial necrosis and severe systemic toxicity are common manifestations of CNF . Review of the literature reveals only seven such cases, with four successful outcomes . The authors present the case of a 50-year-old immunocompetent female with CNF arising from a peritonsillar abscess . Intravenous immunoglobulins in conjunction with surgery and antibiotics were used successfully . The authors also suggest the importance of the early diagnosis, aggressive surgical debridement, broad-spectrum antibiotics, and possible usefulness of the intravenous immunoglobulins in the treatment of CNF, especially when the disease is associated with toxic shock syndrome.

J Clin Microbiol, 2000 Apr, 38(4), 1641 - 4
Molecular characterization of multidrug-resistant Streptococcus pneumoniae isolates in Korea . The Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study Group; Song JH et al.; Pulsed-field gel electrophoresis, ribotyping, and fingerprinting analysis of 22 invasive isolates of multidrug-resistant (MDR) pneumococci from Korea showed that 59 to 82% were genetically related . DNA sequencing of the PBP 2B gene showed relatively uniform alterations in nucleotides (5.4 to 7.8%) and amino acids (3.0 to 4 . 3%), while Asn-276-->Lys, Arg-285-->Cys and Ser-305-->Phe substitutions were unique to Korean MDR strains, suggesting the spread of a few epidemic clones of resistant pneumococci within Korea.

J Clin Microbiol, 2000 Apr, 38(4), 1575 - 80
A novel multiresistant Streptococcus pneumoniae serogroup 19 clone from Washington State identified by pulsed-field gel electrophoresis and restriction fragment length patterns; Luna VA et al.; In 1997, a cluster of multiresistant invasive serogroup 19 pneumococcus infections, including two fatalities, was reported in Washington State . Further investigation identified other cases . Fourteen Washington Streptococcus pneumoniae isolates, four from Alaska, and eight isolates from eastern Canada with reduced penicillin susceptibility (MIC of > or =1 microg/ml) were included in the study . Pulsed-field gel electrophoresis (PFGE) with ApaI, SacII, and SmaI restriction enzymes and IS1167 and mef restriction fragment length polymorphism (RFLP) pattern analysis were performed . Twenty of the 26 isolates had identical or related PFGE patterns, with two or all three enzymes, and identical or related IS1167 RFLP patterns, indicating that they were genetically related . These 20 isolates contained the mef gene conferring erythromycin resistance and had identical mef RFLP patterns . The PFGE and RFLP patterns were distinct from those of six multiresistant clones previously described and suggest that a new multiresistant clone has appeared in Washington, Alaska, and eastern Canada . This newly characterized clone should be included in the Pneumococcal Molecular Epidemiology Network.

J Clin Microbiol, 2000 Apr, 38(4), 1375 - 81
Molecular evolution in a multidrug-resistant lineage of Streptococcus pneumoniae: emergence of strains belonging to the serotype 6B Icelandic clone that lost antibiotic resistance traits; Vilhelmsson SE et al.; Since their first detection in 1988, penicillin-resistant Streptococcus pneumoniae isolates have rapidly spread in Iceland to account for close to 20% of all pneumococcal disease in that country by 1993 . The major component (70%) of the resistant pneumococci identified from 1989 to 1992 was the progeny of a single multidrug-resistant clone (Icelandic clone) with a homogeneous chromosomal macrorestriction profile and identical multilocus enzyme type expressing serotype 6B and resistance to penicillin, tetracycline, chloramphenicol, erythromycin, and trimethoprim-sulfamethoxazole . The rest of the non-penicillin-susceptible isolates included bacteria with serotype 6A and serogroups 19 and 23 . The unique geographic and epidemiological setting and the availability of a complete collection of all non-penicillin-susceptible isolates of S . pneumoniae in Iceland prompted us to carry out a molecular epidemiological study to monitor the fate of the Icelandic clone between 1989 and 1996; in addition, we wished to extend the characterization to representative groups of all non-penicillin-susceptible serotype 6B pneumococci which showed variations in antibiotype and which were recovered in Iceland between late 1989 and the end of 1996 . Also included in the study were non-penicillin-susceptible isolates of serogroup 23 . Pulsed-field gel electrophoresis of SmaI-restricted chromosomal DNA and Southern hybridization with the lytA DNA probe and probes specific for antibiotic resistance genes were used to characterize pneumococcal isolates . The results show that (i) the Icelandic clone remained the predominant type among penicillin-resistant S . pneumoniae through 1996; (ii) the emergence of variants of the Icelandic clone which had lost one or more of the antibiotic resistance phenotypes and/or resistant genes, singly or in combination, was documented during the surveillance period; and (iii) isolates belonging to the internationally spread multidrug-resistant serotype 23F clone were present in the Icelandic collection since late 1989 but did not increase in number during the subsequent years.

J Clin Microbiol, 2000 Apr, 38(4), 1319 - 23
Evaluation of serotype prediction by cpsA-cpsB gene polymorphism in Streptococcus pneumoniae; Lawrence ER et al.; New pneumococcal conjugate vaccines covering a limited number of serotypes are likely to come into widespread use over the next few years . It is unknown what effect this will have on the relative importance of different serotypes as causes of pneumococcal infection . Hence, it will be important to monitor serotype prevalence before, during, and after the introduction of new vaccines . We have investigated the ability of a PCR method based on polymorphisms in two genes common to the different capsule loci to predict the serotype of 93 clinical isolates of Streptococcus pneumoniae submitted to the Central Public Health Laboratory in 1997 . Of 70 isolates with vaccine serotypes, 65 were predicted to belong to the correct serotype; this number was improved to 69 with the inclusion of two additional patterns to the database . Of 23 isolates with other serotypes, 19 were correctly predicted as non-vaccine serotypes, the discrepancy lying with four isolates of 6A (non-vaccine serotype) that were indistinguishable from isolates of 6B (vaccine serotype) . In situations in which culture of the organism is not feasible, this method could potentially be applicable directly to clinical specimens and could be a valuable aid to the surveillance of pneumococcal serotypes.

Genetics, 2000 Apr, 154(4), 1439 - 50
Estimating recombinational parameters in Streptococcus pneumoniae from multilocus sequence typing data; Feil EJ et al.; Multilocus sequence typing (MLST) is a highly discriminatory molecular typing method that defines isolates of bacterial pathogens using the sequences of approximately 450-bp internal fragments of seven housekeeping genes . This technique has been applied to 575 isolates of Streptococcus pneumoniae and identifies a number of discrete clonal complexes . These clonal complexes are typically represented by a single group of isolates sharing identical alleles at all seven loci, plus single-locus variants that differ from this group at only one out of the seven loci . As MLST is highly discriminatory, the members of each clonal complex can be assumed to have a recent common ancestor, and the molecular events that give rise to the single-locus variants can be used to estimate the relative contributions of recombination and mutation to clonal divergence . By comparing the sequences of the variant alleles within each clonal complex with the allele typically found within that clonal complex, we estimate that recombination has generated new alleles at a frequency approximately 10-fold higher than mutation, and that a single nucleotide site is approximately 50 times more likely to change through recombination than mutation . We also demonstrate how to estimate the average length of recombinational replacements from MLST data.

Microbiology, 2000 Mar, 146 ( Pt 3), 687 - 94
Protonmotive force regulates the membrane conductance of Streptococcus bovis in a non-ohmic fashion; Bond DR et al.; Because the DCCD (dicyclohexylcarbodiimide)-sensitive, F-ATPase-mediated, futile ATP hydrolysis of non-growing Streptococcus bovis JB1 cells was not affected by sodium or potassium, ATP hydrolysis appeared to be dependent only upon the rate of proton flux across the cell membrane . However, available estimates of bacterial proton conductance were too low to account for the rate of ATP turnover observed in S . bovis . When de-energized cells were subjected to large pH gradients (2.75 units, or -170 mV), internal pH declined at a rate of 0.15 pH units s(-1) . Based on an estimated cellular buffering capacity of 200 nmol H+ (mg protein)(-1) per pH unit, H+ flux across the cell membrane (at -170 mV) was 108 mmol (g protein)(-1) h(-1) . When potassium-loaded cells were treated with valinomycin in low-potassium buffers, initial K+ efflux generated membrane potentials in close agreement with values predicted by the Nernst equation . These artificial membrane potentials drove H+ uptake, and H+ influx was counterbalanced by a further loss of cellular K+ . Flame photometry indicated that the rate of K+ loss was 215 (+/-26) mmol K+ (g protein)(-1) h(-1) at -170 mV, but the potassium-sensitive fluorescent compound CD222 indicated that this rate was only 110 (+/-44) mmol K+ (g protein)(-1) h(-1) . As pH gradients or membrane potentials were reduced, the rate of H+ flux declined in a non-ohmic fashion, and all rates were <25 mmol (g protein)(-1) h(-1) at a driving force of -80 mV . Previous estimates of bacterial proton flux were based on low and unphysiological protonmotive forces, and the assumption that H+ influx rate would be ohmic . Rates of H+ influx into S . bovis cells {as high as 9x10(-11) mol H+ (cm membrane)(-2) s(-1)} were similar to rates reported for respiring mitochondria, but were at least 20-fold greater than any rate previously reported in lactic acid bacteria.

Eur J Clin Microbiol Infect Dis, 2000 Feb, 19(2), 137 - 9
In vitro susceptibility to gemifloxacin and trovafloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin; Fuentes F et al.; The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC > or =2 microg/ml; 30 strains with intermediate resistance {MIC 2 microg/ml} and 43 strains with complete resistance {MIC > or =4 microg/ml}) was determined . Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested . The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P< or =0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 microg/ml for gemifloxacin vs . 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 microg/ml for trovafloxacin in the 2, 4, 8 and > or =16 microg/ml ciprofloxacin MIC categories, respectively) . Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (> or =2 microg/ml), whereas all strains were inhibited by 0.25 microg/ml of gemifloxacin.

Eur J Clin Microbiol Infect Dis, 2000 Feb, 19(2), 128 - 31
Comparison of three methods for identification of Streptococcus milleri group isolates to species level; Limia A et al.; A collection of 180 clinical isolates of Streptococcus milleri group were identified to species level using two phenotypic methods (a commercial system and the reference method based on differential phenotypic reactions) and a genotypic method (hybridisation of the 16S rRNA gene with species-specific probes) in order to evaluate the performance of the respective methods . A high level of agreement (80%) was observed between the results of the reference method and the genotypic method . The highest level of agreement was found for the species Streptococcus anginosus (83%), a high level of agreement (76%) also being achieved for Streptococcus constellatus and Streptococcus intermedius . The sensitivity of the commercial system compared to the genotypic method was 76% overall, but it was low (57.5%) for Streptococcus intermedius . Twenty-five strains belonged to the recently described CI strains.

Cent Afr J Med, 1999 Apr, 45(4), 100 - 2
Penicillin resistant Streptococcus pneumoniae isolates in Harare, Zimbabwe; Simango C et al.; OBJECTIVE: To determine the susceptibility of Streptococcus pneumoniae isolates to penicillin and other antimicrobial drugs . DESIGN: This was a laboratory based study . SETTING: Department of Medical Laboratory Sciences, University of Zimbabwe and the Bacteriology Unit, Public Health Laboratories, Harare . SUBJECTS: 71 S . pneumoniae isolates from Parirenyatwa and Harare hospitals . MAIN OUTCOME MEASURES: Penicillin resistance, MIC of penicillin to S . pneumoniae, multi-drug resistance . RESULTS: 71 S . pneumoniae isolates were tested for their susceptibilities to penicillin G, erythromycin, tetracycline, ampicillin, ciprofloxacin and clindamycin . Five (7%) of the isolates were resistant to penicillin G and were also all resistant to erythromycin . Isolates resistant to other antibiotics were; tetracycline (4), ampicillin (3) and ciprofloxacin (2) . The five isolates that were resistant to penicillin G showed resistance to two or more antibiotics . Four S . pneumoniae isolates were designated highly resistant to penicillin (MIC > or = 2 micrograms/ml) and one isolate was designated intermediate in resistance to penicillin (MIC between 0.1 and 1.0 microgram/ml) . CONCLUSIONS: A low percentage of S . pneumoniae isolates were resistant to penicillin and were also resistant to erythromycin . The penicillin resistant strains showed multi-drug resistance.

Jpn J Antibiot, 1999 Sep, 52(9), 563 - 70
{Investigation of the antibacterial activity of faropenem against Streptococcus pneumoniae}; Hanaki H et al.; We evaluated the antibacterial activity of faropenem against penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-resistant S . pneumoniae (PRSP) . It was shown that the minimum inhibitory concentrations against 90% of the clinically isolated strains (MIC90) of faropenem, penicillin G, cefaclor, cefcapene, and cefditoren against PSSP were 0.032, 0.063, 2, 0.25, and 0.125 micrograms/ml, respectively . While those against PRSP were 0.5, 2, > 128, 1, and 1 micrograms/ml, respectively . Furthermore, we evaluated the bactericidal activity, at the level of 1/4, 1, and 4 MIC, of faropenem and the above four reference antibacterial agents against PSSP and PRSP . Against PSSP No . 127, a sensitive strain to both penicillin G and cefcapene, faropenem showed almost the same bactericidal activity as those of reference agents . Against PSSP No . 108, a penicillin-susceptible and cephem-resistant strain, and PRSP No . 57, a resistant strain to both of penicillin and cephem, faropenem of 1 MIC showed bactericidal activity, but reference agents needed 4 MIC to show bactericidal activity.

J Formos Med Assoc, 2000 Jan, 99(1), 18 - 23
Pneumonia caused by penicillin-nonsusceptible Streptococcus pneumoniae: clinical characteristics, prognostic factors, and outcomes; Wu TT et al.; BACKGROUND AND PURPOSE: Pneumococcal pneumonia caused by penicillin-nonsusceptible Streptococcus pneumoniae (PNSSP) is increasing worldwide . To better understand this infection, patients with pneumococcal pneumonia treated at National Taiwan University Hospital during a 5-year period were evaluated to determine the clinical characteristics, prognostic factors, and outcomes of the infection . METHODS: Eighty-one patients with 81 episodes of pneumococcal pneumonia diagnosed from January 1993 to December 1997 were analyzed retrospectively . Patients were categorized into two groups according to susceptibility results . Differences between groups were evaluated with Student's t-test and the chi-square test . Univariate analysis was used to identify factors associated with mortality . RESULTS: Infections were caused by penicillin-susceptible S . pneumoniae (PSSP) in 57 (70%) patients and by PNSSP in the remaining 24 (30%) . Nosocomial acquisition was more common in PNSSP (25%) than in PSSP patients (10%) (p = 0.05), while the frequency of bacteremia (54% vs 60%) and the mortality rate (46% vs 32%) did not differ significantly between the PNSSP and PSSP groups . Among the 24 patients with pneumonia caused by PNSSP, those 65 years of age or older had a lower incidence of bacteremia (4/14, 29%) than those who were younger (9/10, 90%) (p = 0.03) . In patients with pneumonia caused by PNSSP, the outcome was not significantly related to the treatment regimen (penicillin vs nonpenicillin beta-lactam antibiotics or vancomycin, 33% vs 47%; p = 0.4) . The only factors associated with mortality from these infections were shock (p = 0.003) and multilobar consolidation (p = 0.01) at the time of admission . CONCLUSIONS: These data suggest that the clinical outcome of pneumococcal pneumonia is more closely related to the clinical condition at presentation than the susceptibility status of the pneumococcus.

Pathology, 2000 Feb, 32(1), 46 - 8
Group B streptococcus screening in pregnant women: a comparison of three media; Mukerjee C et al.; This study compared the relative isolation rate of Group B Streptococcus (GBS) from 663 low vaginal swabs, collected from antenatal patients, on three media: horse blood agar plus neomycin (75 mg/l) (Neo), Islam agar (Islam) and Islam agar plus nalidixic acid (15 mg/l) and colistin sulphate (10 mg/l) (Islam Plus) . One hundred and forty-seven (22%) GBS were isolated . At 24 hours the isolation rate was highest using Neo, but within 72 hours there was little difference . The isolation rates for Neo, Islam and Islam Plus at 24 hours were 124 (18.7%), 103 (15.6%), 109 (16.4%) (P < 0.05); at 48 hours 125 (18.9%), 116 (17.5%), 121 (18.1%) (P > 0.1); and at 72 hours 125 (18.9%), 121 (18.3%) and 127 (19.1%) (P > 0.1), respectively . Twenty-two isolates were missed on Neo, 26 on Islam and 20 on Islam Plus . Of those missed on Islam agars, 12 failed to produce pigment and were only detected on Neo . The disadvantage of Neo is the need to perform additional tests to confirm the identity as GBS . In the present study 100 suspicious colonies were identified as Group D.

J Biochem (Tokyo), 2000 Apr, 127(4), 695 - 702
Chimeric glycosaminoglycan oligosaccharides synthesized by enzymatic reconstruction and their use in substrate specificity determination of Streptococcus hyaluronidase; Takagaki K et al.; A method was developed for the reconstruction of glycosaminoglycan (GAG) oligosaccharides using the transglycosylation reaction of an endo-beta-N-acetylhexosaminidase, testicular hyaluronidase, under optimal conditions . Repetition of the transglycosylation using suitable combinations of various GAGs as acceptors and donors made it possible to custom-synthesize GAG oligosaccharides . Thus we prepared a library of chimeric GAG oligosaccharides with hybrid structures composed of disaccharide units such as GlcA-GlcNAc (from hyaluronic acid), GlcA-GalNAc (from chondroitin), GlcA-GalNAc4S (from chondroitin 4-sulfate), GlcA-GalNAc6S (from chondroitin 6-sulfate), IdoA-GalNAc (from desulfated dermatan sulfate), and GlcA-GalNAc4,6-diS (from chondroitin sulfate E) . The specificity of the hyaluronidase from Streptococcus dysgalactiae (hyaluronidase SD) was then investigated using these chimeric GAG oligosaccharides as model substrates . The results indicate that the specificity of hyaluronidase SD is determined by the following restrictions at the nonreducing terminal side of the cleavage site: (i) at least one disaccharide unit (GlcA-GlcNAc) is necessary for the enzymatic action of hyaluronidase SD; (ii) cleavage is inhibited by sulfation of the N-acetylgalactosamine; (iii) hyaluronidase SD releases GlcA-GalNAc and IdoA-GalNAc units as well as GlcA-GlcNAc . At the reducing terminal side of the cleavage site, the sulfated residues on the N-acetylgalactosamines in the disaccharide units were found to have no influence on the cleavage . Additionally, we found that hyaluronidase SD can specifically and endolytically cleave the internal unsulfated regions of chondroitin sulfate chains . This demonstration indicates that custom-synthesized GAG oligosaccharides will open a new avenue in GAG glycotechnology.

Acta Crystallogr D Biol Crystallogr, 2000 Apr, 56 ( Pt 4), 460 - 3
Structural studies of streptococcus agalactiae hyaluronate lyase; Jedrzejas MJ et al.; The bacteria Streptococcus agalactiae, part of normal human flora, produce an enzyme, hyaluronate lyase, which appears to contribute to the invasive capacity of this pathogen by degrading hyaluronan and chondroitin sulfates of the extracellular matrix of host tissues . The native enzyme, the product of the hylB(3502) allele, has a molecular mass of 111 kDa but undergoes an autocatalytic conversion to a smaller enzymatically active 92 kDa form . To initiate the determination of the catalytic mechanism of action of these enzymes, the 111 and 92 kDa enzymes were crystallized by a vapor-diffusion method using polyethylene glycol monomethyl ether 5000 and potassium thiocyanate as precipitating agents . The 111 kDa enzyme crystals are of poor quality and diffract X-rays to a very low resolution . However, the crystals of the truncated 92 kDa enzyme diffract X-rays to 2.1 A resolution . The crystal symmetry is C222(1) and the unit-cell parameters are a = 51.69, b = 157.03, c = 239.20 A (alpha = beta = gamma = 90 degrees ) . The V(m) of 2.64 A(3) Da(-1) is consistent with the presence of one molecule of hyaluronate lyase in the asymmetric unit and a crystal solvent content of 53% . An isomorphous ethylmercuricthiosalicylic acid heavy-atom derivative diffraction data set has been obtained in order to solve the structure.

J Microbiol Methods, 2000 Mar, 40(1), 79 - 88
Development and evaluation of a broad-range PCR-ELISA assay with Borrelia burgdorferi and Streptococcus pneumoniae as model organisms for reactive arthritis and bacterial meningitis; Fischer-Romero C et al.; We have developed an assay based on a 16S rDNA broad-range amplification system followed by species-specific detection with a commercially available PCR-ELISA kit . B . burgdorferi and S . pneumoniae were used as model systems for arthritis and meningitis, respectively . The sensitivity of the B . burgdorferi assay was comparable to that of a species-specific PCR, whereas for S . pneumoniae the detection limit was one to three organisms as determined by plate counts . To specifically differentiate two species, two discontinuously located nucleotide differences in the region complementary to the capture probe are required during the detection step with the PCR-ELISA kit . A preliminary clinical evaluation was performed with eight specimens (joint and cerebrospinal fluids) previously shown to contain B . burgdorferi DNA . Except for one sample which was positive by the broad-range PCR-ELISA system only, the results were in agreement with those obtained by B . burgdorferi species-specific PCR . None of the 23 control samples were positive by either method . Thus, broad-range amplification in combination with the PCR-ELISA kit promises to be a sensitive and specific format for the detection of agents causing reactive arthritis, meningitis or other diseases associated with a limited number of different bacteria.

Cancer, 2000 Apr 1, 88(7), 1710 - 4
Feasibility of oral ciprofloxacin for the outpatient management of febrile neutropenia in selected children with cancer; Aquino VM et al.; BACKGROUND: Children with cancer who develop an episode of chemotherapy-induced febrile neutropenia usually are admitted to the hospital for intravenous empiric antibiotic therapy . In the current study, the authors examined the use of ciprofloxacin as outpatient management in selected patients with fever during an episode of neutropenia . METHODS: Febrile neutropenic patients with a diagnosis of cancer were eligible for outpatient management with oral ciprofloxacin if they appeared well and demonstrated the following characteristics: age 1-21 years, malignancy in remission, absolute phagocyte count > 100/mm(3), > 7 days since the initiation of the last course of chemotherapy, and reliable parents . Eligible children received a single dose of ceftazidime and were observed for 2-23 hours . Patients were discharged receiving oral ciprofloxacin (20/mg/kg/day divided in 2 doses) until the patient was afebrile for 24 hours, had sterile blood cultures, and had evidence of bone marrow recovery . Patients were admitted if they appeared toxic, had positive blood cultures, or were febrile for >/= 5 days . RESULTS: Forty-five evaluable episodes occurred in 32 children . Forty of the 45 patients (89%) were treated successfully in the outpatient setting . The 95% lower confidence bound on the proportion of successful outcomes was 70% . Five children required hospitalization: 2 due to noncompliance, 1 to receive intravenous acyclovir for herpes zoster, and 2 (4%) whose blood cultures were positive for Streptococcus viridans and S . pneumoniae . All had uncomplicated hospitalizations . CONCLUSIONS: The current study demonstrates that very carefully selected, low risk patients with febrile neutropenia may be treated successfully without hospitalization using oral ciprofloxacin . Additional research is required to refine further the optimal criteria for the selection of appropriate patients for outpatient management .

Int J Infect Dis, 2000, 4(2), 91 - 5
Ten-year review of invasive pneumococcal diseases in children and adults from Uruguay: clinical spectrum, serotypes, and antimicrobial resistance; Hortal M et al.; OBJECTIVES: Since 1987, the Reference Laboratory of the Ministry of Health of Uruguay has been monitoring infections due to Streptococcus pneumoniae in patients under 5 years of age, in those between 5 to 14 years of age, and in adults . The purpose of the present study was to retrospectively analyze a 10-year collection of invasive S . pneumoniae isolates from children 5 to 14 years of age and adults . METHODS: The Reference Children's Hospital, Pasteur Hospital, and two private hospitals in Montevideo as well as four hospitals located in other representative areas of the country participated in the pneumococcal surveillance program . Based on the information available at the Microbiology Department of the Central Public Health Laboratory (demographic data, date and site of isolate, and clinical diagnosis), all patients with an invasive pneumococcal disease were recorded . Pneumonia was clinically and radiologically diagnosed and etiology was assessed by isolation of S . pneumoniae from blood or pleural fluid . All specimens were collected at the Emergency Service . Capsular serotyping and antimicrobial susceptibilities were determined for each isolate . RESULTS: During the 10-year period, 228 invasive S . pneumoniae were identified and included in the study (blood, n = 129; cerebrospinal fluid {CSF}, n = 73; pleural fluid, n = 20; peritoneal fluid, n = 3; synovial fluid, n = 1; pericardic fluid, n = 1; abscess, n = 1) . The most frequent clinical presentations were pneumonia (n = 71) and meningitis (n = 69) . Thirty-five adults had an underlying condition including, four with malignancies, four with lupus, two with human immunodeficiency virus (HIV)-infected, and two patients in hemodialysis among others . Eighteen of the 228 patients died (7.9% fatality rate), but only four of these had an underlying condition . Eleven fatal cases were attributable to meningitis (2 children, 9 and 11 years old; 9 adults, mean age, 59 y) . Four patients with pneumonia and three with sepsis died, including a splenectomized woman . Nine different capsular serotypes (1, 5, 7, 9, 12, 15, 19A, 20, and 23A) were identified among the 18 fatal cases . Resistance to penicillin, generally combined with trimethoprim-sulfamethoxazole, fluctuated annually, not surpassing 10% . CONCLUSIONS: The study results indicated that 96% of the serotypes involved in severe pneumococcal diseases were included in the 23-valent vaccine and that S . pneumoniae resistance to penicillin was moderate.

Biosci Biotechnol Biochem, 2000 Feb, 64(2), 223 - 8
Purification and partial characterization of a novel glucanhydrolase from Lipomyces starkeyi KSM 22 and its use for inhibition of insoluble glucan formation; Ryu SJ et al.; A novel glucanhydrolase from a mutant of Lipomyces starkeyi ATCC 74054 was purified . The single protein (100 kDa) showed either dextranolytic or amylolytic activity . We referred to the glucanhydrolase as a DXAMase . The DXAMase was produced in a starch medium and it was 3.75-fold more active for hydrolysis of the purified insoluble-glucan of Streptococcus mutans than Penicillium funiculosum dextranase . Aggregation of S . mutans cells with dextran and adherence to glass were eliminated by incubating with the DXAMase . The addition of DXAMase (0.1 IU/ml) to the mutansucrase reaction digest with sucrose reduced the formation of insoluble-glucan about 80% . Also the DXAMase (0.5 IU/ml) removed 80% of the pre-formed sucrose-dependent adherent film . These in vitro properties of L . starkeyi KSM 22 DXAMase are desirable for its application as a dental plaque control agent.

Zhonghua Kou Qiang Yi Xue Za Zhi, 1997 Mar, 32(2), 102 - 4
{Ultrastructure of adherence of Streptococcus mutans MT8148 and its glucosyltransferase deficient mutants}; Bian Z et al.; The ultrastructure of adherence of Streptococcus mutans MT8148 and its glucosyltransferase deficient mutants were compared by Scanning Electronic Microscope . Four patterns of adherence of tested strains in the presence of sucrose were observed . These results suggest that the cell-associated GTase is responsible for firm aggregation of cells . However, cell free GTase is also important in aggregation between cells.

Respirology, 2000 Mar, 5(1), 59 - 64
A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital; Watanabe H et al.; OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae . METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997 . There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP) . RESULTS: Both the mean age and the underlying disease states did not differ between the two groups . However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively . The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively . Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems . Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) {corrected} . CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia . Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died) . As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present . However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.

Biochemistry, 2000 Mar 28, 39(12), 3327 - 35
Role of glutamate-268 in the catalytic mechanism of nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans; Marchal S et al.; Nonphosphorylating nicotinamide adenine dinucleotide (phosphate)- {NAD(P)-} dependent aldehyde dehydrogenases share a number of conserved amino acid residues, several of which are directly implicated in catalysis . In the present study, the role of Glu-268 from nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) from Streptococcus mutans was investigated . Its substitution by Ala resulted in a k(cat) decrease by 3 orders of magnitude . Pre-steady-state analysis showed that, for both the wild-type and E268A GAPNs, the rate-limiting step of the reaction is associated with deacylation . The pH dependence of the rate of acylation of wild-type GAPN is characterized by the contributions of distinct enzyme protonic species with two pK(a)s of 6.2 and 7.5 . Substitution of Glu-268 by Ala resulted in a monosigmoidal pH dependence of the rate constant of acylation with a pK(a) of 6.2, which suggested the assignment of pK(a) 7.5 to Glu-268 . Moreover, the E268A substitution did not significantly affect the efficiency of acylation of GAPN, showing that Glu-268 is not critically involved in the acylation, which includes Cys-302 nucleophilic activation and hydride transfer . On the contrary, the drastic decrease of the steady-state rate constant for the E268A GAPN demonstrated the essential role of Glu-268 in the deacylation . At basic pH, the solvent isotope effect of 2.3, characterized by a unique pK(a) of 7.7, and the linearity of the proton inventory showed that the rate-limiting process for deacylation is associated with the hydrolysis step and suggested that the glutamate form of Glu-268 acts as a base catalyst in this process . Surprisingly, the double-sigmoidal form of the pH-steady-state rate constant profile, characterized by pK(a) values of 6.1 and 7.4, revealed the high efficiency of the deacylation even at pH lower than 7.4 . Therefore, we propose that the major role of Glu-268 is to promote deacylation through activation and orientation of the attacking water molecule, and in addition to act as a base catalyst at basic pH . From these results in relation to those recently described {Marchal, S., and Branlant, G . (1999) Biochemistry 38, 12950-12958}, a scenario for the chemical catalysis of GAPN is proposed.

J Endod, 1999 Nov, 25(11), 731 - 4
Leakage in roots coronally sealed with different temporary fillings; Barthel CR et al.; This study was aimed at determining the ability of different coronal temporary fillings to prevent corono-apical penetration of bacteria . A total of 103 human teeth, including three controls, were instrumented, obturated with gutta-percha, coronally sealed with either Cavit, Intermediate Restorative Material (IRM), glass-ionomer cement, Cavit/glass-ionomer cement, or IRM/glass-ionomer cement, respectively . Each root was fixed with wax between two chambers: the coronal chamber harboring soy broth with 10(8) colony-forming units of Streptococcus mutans/ml, the apical chamber containing sterile soy broth . The latter was checked daily for turbidity, indicating corono-apical penetration of bacteria . The Cavit group, the IRM group, and the Cavit/glass-ionomer cement group showed significantly more leakage than the glass-ionomer cement group of the IRM/glass-ionomer cement group . If a sample leaked, all except one (IRM/glass-ionomer cement) leaked before day 12 . This in vitro study seems to indicate that only glass-ionomer cement and IRM combined with glass-ionomer cement may prevent bacterial penetration to the periapex of root-filled teeth over a 1-month period.

J Endod, 1999 Nov, 25(11), 722 - 7
Development of a clindamycin-impregnated fiber as an intracanal medication in endodontic therapy; Gilad JZ et al.; The effectiveness of traditional endodontic intracanal medications in reducing bacterial numbers and preventing acute flare-ups and pain continues to be questioned . In the present study, a new local delivery device was developed that releases a substantive dose of clindamycin into root canals . Clindamycin-impregnated ethylene vinyl acetate (EVA) fibers were produced, and the sensitivity of common endodontic microbes to the fibers were established . An in vitro model was developed to persistently infect 32 extracted human teeth with endodontic pathogens to test the efficacy of the clindamycin/EVA fibers in reducing the number of colony-forming units . The clindamycin/EVA fibers were shown to be effective in reducing growth of common endodontic microbes on blood agar plates, and in significantly reducing growth of Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus intermedius in extracted human teeth, thus indicating merit in further exploring the potential of these fibers as intracanal medications.

J Endod, 1999 Dec, 25(12), 782 - 5
In vitro antimicrobial effect of RC-Prep within dentinal tubules; Heling I et al.; The antimicrobial effect of RC-Prep and its components--10% urea peroxide, 15% EDTA, and glycol--were evaluated individually, in vitro, within dentinal tubules . Standardized bovine incisor root specimens that had been infected with either Staphylococcus aureus or Streptococcus peltzer were incubated with each agent for 10 and 45 min . After exposure to the agent, dentin samples were collected from within the lumina using ISO 23 to 31 burs . Dentin powder samples were incubated with bacterial broth, and the amount of bacteria present was assessed by spectrophotometry . All agents tested were more effective in killing bacteria after incubation for 45 min than after 10 min.

J Agric Food Chem, 2000 Mar, 48(3), 909 - 14
Namibian chewing stick, Diospyros lycioides, contains antibacterial compounds against oral pathogens; Cai L et al.; The twigs of Diospyros lycioides, a plant commonly known as "muthala", are frequently used as chewing sticks for the cleaning of teeth by rural and urban people in Namibia . Preliminary studies showed that a methanol extract of D . lycioides inhibited growth of selected oral pathogens . Subsequent bioassay-guided fractionation led to the isolation of four novel bioactive naphthalene glycosides, diospyrosides A, B, C, and D (1-4), and two known bioactive naphthoquinones, juglone (5) and 7-methyljuglone (6) . The structures of the new compounds were elucidated using spectroscopic techniques including 1D and 2D NMR . These compounds inhibited the growth of oral cariogenic bacteria (Streptococcus mutans and Streptococcus sanguis) and periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) at minimum inhibitory concentrations ranging from 0.019 to 1.25 mg/mL . Juglone exhibited the strongest inhibitory activity among these compounds.

Res Microbiol, 2000 Jan-Feb, 151(1), 29 - 36
Characterization of group A streptococcal strains Sv and Su: determination of emm gene typing and presence of small vir regulon; Hong K; The emm gene typing of GAS (group A streptococcus) strains Sv and Su and the molecular structure of the vir regulon were decided . An emm(-like) gene from the chromosomal DNA of GAS strain Sv was amplified with forward and reverse primers, which were selected from the best conserved portion in leader sequences of different strains and the C-terminal conserved portion, respectively, for determination of the M protein gene type . Strain Sv was defined as serotype M23, because deduced N-terminal amino acid positions of the products are identical to those of the M type 23 (emml) gene derived from GAS strain M23-MEMPHIS (M serotype 23, GenBank accession number U11953) . When the vir regulon of strain Sv was examined by polymerase chain reaction mapping and compared with that of GAS strain Su, they had a similar size in length . In addition, when sequencing analysis of the DNA fragment of 4791 base pairs (bp) encoding three open reading frames (orf, mga, and emm) and the upstream region of scpA from genomic DNAs of both strains was performed, the sequence of the DNA from strain Sv was, except for 1 bp (T for C at position 4124), identical to that of the DNA from strain Su . These data show that both strains possess the genes in the order of mga (virR or mry) -emm -scpA designated as the small vir regulon . The effect of the formation of alternative pathway C3 convertase of complement on the GAS strains Sv and Su was also examined . When GAS strains Sv and Su were incubated in NHS containing radiolabeled C3 in the presence of Mg-EGTA, binding of C3 to Su bacteria was dose-dependent, whereas less binding of C3 to Sv bacteria was seen . Taken together, the data suggest that M protein could be expressed on the surface of the Sv bacteria, but not on the Su bacteria.

Carbohydr Res, 2000 Jan 29, 324(1), 17 - 29
Bivalency and epitope specificity of a high-affinity IgG3 monoclonal antibody to the Streptococcus group A carbohydrate antigen . Molecular modeling of a Fv fragment; Pitner JB et al.; The binding of Strep 9, a mouse monoclonal antibody (mAb) of the IgG3 subclass directed against the cell-wall polysaccharide of Group A Streptococcus (GAS), has been characterized . The intact antibody and proteolytic fragments of Strep 9 bind differently to GAS: the intact mAb and F(ab)2' have greater affinity for the carbohydrate epitope than the monomeric Fab or F(ab)' . A mode of binding in which Strep 9 binds bivalently to portions of the polysaccharide on adjacent chains on GAS is proposed . A competitive ELISA protocol using a panel of carbohydrate inhibitors shows that the branched trisaccharide, beta-D-GlcpNAc-(1-->3)-{alpha-L-Rhap-(1-->2)}-alpha-L-Rhap, and an extended surface are key components of the epitope recognized by Strep 9 . Microcalorimetry measurements with the mAb and two synthetic haptens, a tetrasaccharide and a hexasaccharide, show enthalpy-entropy compensation as seen in other oligosaccharide-protein interactions . Molecular modeling of the antibody variable region by homology modeling techniques indicates a groove-shaped combining site that can readily accommodate extended surfaces . Visual docking of an oligosaccharide corresponding to the cell-wall polysaccharide into the site provides a putative model for the complex, in which a heptasaccharide unit occupies the site and the GlcpNAc residues of two adjacent branched trisaccharide units occupy binding pockets within the groove-shaped binding site.

J Biol Chem, 2000 Mar 24, 275(12), 8970 - 4
Salivary film expresses a complex, macromolecular binding site for Streptococcus sanguis; Gong K et al.; Teeth in the oral cavity are coated with a salivary film or pellicle, which lacks apparent intermolecular organization . This heterogeneous film facilitates binding of early commensal colonizing bacteria, including Streptococcus sanguis . To test the hypothesis that sufficient intermolecular organization exists in salivary films to form binding sites for S . sanguis, an in vitro model of saliva-coated teeth was probed with murine anti-idiotypical monoclonal antibodies (mAb2, anti-ids) . The anti-ids were harvested from hybridomas that were developed in response to first generation murine hybridomas that produced anti-S . sanguis adhesin monoclonal antibodies (mAb1) . The anti-ids (i) reacted with experimental salivary films and inhibited S . sanguis adhesion in a dose-dependent fashion . In Western blots, the anti-ids (ii) recognized a high molecular weight salivary antigen and (iii) secretory IgA (sIgA) light chain and alpha-amylase . After isolation by gel filtration from whole saliva or mixed secretory IgA and alpha-amylase, the high molecular weight component, containing amylase activity and sIgA, bound to hydroxyapatite to promote adhesion of S . sanguis . Therefore, a complex enriched in secretory immunoglobulin A and alpha-amylase forms a S . sanguis-binding site.

Infect Immun, 2000 Apr, 68(4), 2286 - 93
Intracellular trafficking and killing of Streptococcus pneumoniae by human alveolar macrophages are influenced by opsonins; Gordon SB et al.; Human alveolar macrophages (HAM) are the major resident phagocytic cells of the gas-exchanging areas of the lung . Following contact with macrophages, bacteria enter phagosomes, which gradually acquire the characteristics of terminal phagolysosomes, with incorporation of lysosome-associated membrane protein (LAMP) . We measured the binding of type 1 Streptococcus pneumoniae to the surface of HAM and then measured subsequent internalization and phagosomal incorporation of LAMP-1 under various opsonic conditions . Opsonization with serum containing immunoglobulin resulted in significantly greater binding of pneumococci to HAM compared with opsonization with immunoglobulin G (IgG)-depleted serum containing complement, which in turn resulted in marginally increased binding over that observed in the absence of opsonization . Internalization of opsonized S . pneumoniae gradually increased to a maximum of 20% of bound bacteria by 120 min of warm incubation, with 20% of internalized pneumococci being localized within LAMP-containing compartments by 80 min . Internalization of opsonized S . pneumoniae by HAM correlated with a reduction of bacterial viability . When inocula were adjusted so that pneumococcal binding under different conditions was equalized, subsequent internalization, trafficking to LAMP-containing compartments, and reduction of bacterial viability were less efficient in the absence of opsonization than that observed following opsonization with adsorbed or IgG-replete adsorbed serum . Once bound to the surface of HAM, pneumococci opsonized with adsorbed serum with or without IgG were internalized, processed, and killed equally well . In conclusion, binding, intracellular trafficking, and killing of S . pneumoniae by HAM are each significantly increased by opsonization with serum containing immunogloblin and/or complement.

Infect Immun, 2000 Apr, 68(4), 2167 - 70
Survival of group B streptococcus type III in mononuclear phagocytes: differential regulation of bacterial killing in cord macrophages by human recombinant gamma interferon and granulocyte-macrophage colony-stimulating factor; Marodi L et al.; Phagocytic and killing capacities of resident and cytokine-activated human macrophages against group B Streptococcus (GBS) type III were studied . Evidence is presented that monocyte-derived macrophages from cord and adults ingest serum-opsonized GBS but that killing of bacteria was negligible in resident cells . Treatment of adult macrophages with recombinant human gamma interferon (rhIFN-gamma; 100 U/ml) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml) resulted in significant increases of killing of GBS (P < 0.01 for each) . The killing capacity of cord macrophages treated with rhGM-CSF was also enhanced compared to that of untreated cells (P < 0.01) . However, treatment with rhIFN-gamma resulted in only a moderate increase in the capacity of cord macrophages to kill GBS (P > 0.1) . These results mirrored the effect of rhIFN-gamma on candidacidal capacities of cord and adult macrophages, reported earlier from our laboratory . These data indicate differential modulation of neonatal macrophages by rhGM-CSF and rhIFN-gamma . We suggest that administration of rhGM-CSF to neonates with invasive GBS disease may enhance host resistance to these bacteria.

Infect Immun, 2000 Apr, 68(4), 1879 - 83
Human dendritic cells are superior to B cells at presenting a major histocompatibility complex class II-restricted heterologous antigen expressed on recombinant Streptococcus gordonii; Corinti S et al.; Bacteria are being actively investigated as vaccine carriers for inducing or boosting protective immune responses . In this study, human monocyte-derived dendritic cells (DCs) and normal B cells were compared for their capacity to present the C fragment of tetanus toxin (TTFC), expressed on the surface of recombinant Streptococcus gordonii, to specific CD4(+) T lymphocytes . DCs were more efficient than B cells at presenting soluble TTFC and remarkably more capable of presenting bacterium-associated TTFC both in terms of the amount of antigen required to obtain a given T-cell response and on a per-cell basis . This difference was associated with a much lower capacity of B cells to endocytose soluble TTFC and phagocytose recombinant S . gordonii . In addition, S . gordonii induced the phenotypic maturation of DCs but not of B cells . The results thus indicate that DCs but not B cells play a crucial role in the amplification of class II-restricted immune responses induced by immunization with recombinant gram-positive bacteria.

Infect Immun, 2000 Apr, 68(4), 1820 - 6
Production of protective human antipneumococcal antibodies by transgenic mice with human immunoglobulin loci; Russell ND et al.; Infections with Streptococcus pneumoniae remain a significant cause of morbidity and mortality . To gain insight into structure-function relationships for human antibodies to pneumococcal capsular polysaccharide (PPS), we studied the response of transgenic mice reconstituted with human immunoglobulin loci, XenoMouse, to PPS antigens in a pneumococcal vaccine . Enzyme-linked immunosorbent assays of sera from mice vaccinated with a 23-valent pneumococcal vaccine revealed that they produced serotype-specific human antibodies, with the greatest response being to the PPS of serotype 3 (PPS 3) . Molecular sequence analysis of three monoclonal antibodies (MAbs) to PPS 3 generated from lymphoid cells from mice vaccinated with a 23-valent pneumococcal vaccine or a PPS 3-bovine serum albumin conjugate revealed that they all used heavy-chain immunoglobulin genes from the V(H)3 family, two expressed light chain genes from the human Vkappa1 family, and one expressed a mouse lambda light chain . The protective efficacy of the two MAbs was examined in mice . A 10-microgram dose of both, and a 1-microgram dose of one, significantly prolonged survival from a lethal serotype 3 infection in CBA/N mice . Our data show that XenoMouse mice produced protective, serotype-specific human antibodies to PPS 3, and they lend support to the proposal that these animals represent a useful model to study the human antibody response to PPS antigens.

Infect Immun, 2000 Apr, 68(4), 1796 - 805
Monoclonal antibody-mediated modulation of the humoral immune response against mucosally applied Streptococcus mutans; Brady LJ et al.; Systemic immunization with antigen coupled to monoclonal antibody (MAb) has been used by several investigators to increase the number of MAb-producing hybridomas against an antigen and to elicit antibodies specific for poorly immunogenic epitopes . This strategy has implications for vaccine design in that protective immunity is not necessarily directed at immunodominant epitopes of pathogens and may be improved by deliberately shifting the immune response toward subdominant epitopes . To our knowledge, no studies to date have addressed the potential for immunomodulatory activity mediated by MAbs bound to mucosally applied antigen . To test whether administration of an exogenous MAb directed against a streptococcal surface protein could influence the humoral immune response, BALB/c mice were immunized orally by gastric intubation or intranasally with Streptococcus mutans alone or S . mutans complexed with a MAb directed against the major surface protein P1 . Significant changes in the subclass distribution, as well as the specificity, of anti-P1 serum immunoglobulin G antibodies were demonstrated in groups of mice which received S . mutans coated with the anti-P1 MAb versus those which received S . mutans alone . Alterations in the humoral immune response were dependent on the amount of anti-P1 MAb used to coat the bacteria . In addition, differences in the anti-P1 immune responses were observed between groups of mice immunized via oral versus intranasal routes . In summary, an exogenous MAb complexed with a streptococcal antigen prior to mucosal immunization can influence the immunoglobulin isotype and specificity of the host humoral immune response against the antigen.

Antimicrob Agents Chemother, 2000 Apr, 44(4), 1010 - 8
In vivo activity and pharmacokinetics of ziracin (SCH27899), a new long-acting everninomicin antibiotic, in a murine model of penicillin-susceptible or penicillin-resistant pneumococcal pneumonia; Wang E et al.; The effectiveness of ziracin (SCH27899), a novel everninomicin, was at first investigated against lethal pneumonia caused by a penicillin-susceptible Streptococcus pneumoniae strain . A single intravenous injection of ziracin at a dose of 60 mg/kg of body weight given at 18 h postinfection protected 100% mice and led to the complete clearance of bacteria from their lungs . The activity of ziracin was observed to be the same as that of ceftriaxone: the 50% protective doses (PD(50)s) of ziracin and ceftriaxone were 24.8 and 24.6 mg/kg, respectively . Evaluation of this therapy with leukopenic mice showed that a single injection of ziracin protected 75% of these mice . A delay in therapy with ziracin, which was initiated at 48 h postinfection with 30 mg/kg given once daily for 3 days, resulted in an 83% survival rate of immunocompetent mice . The efficacy of ziracin was further compared to that of vancomycin against lethal pneumonia caused by a penicillin-resistant S . pneumoniae strain in leukopenic mice . The PD(50)s of ziracin and vancomycin were 40.5 and 44.2 mg/kg, respectively . Treatment with ziracin at 30 mg/kg once daily for 2 days (initiated 18 h postinfection) yielded an 83% survival rate and achieved complete eradication of the bacteria . The results were the same as those obtained with vancomycin administered at 15 mg/kg twice daily for 2 days . It is notable that the high survival rates for mice treated with ziracin were associated with effective eradication of the bacteria and rapid recovery of pulmonary tissues from pneumonia . The pharmacokinetic properties of ziracin, ceftriaxone, and vancomycin were estimated following intravenous administration of a single dose of 30 mg/kg to immunocompetent mice . The half-life of ziracin was observed to be longer than those of ceftriaxone and vancomycin (2.3 h versus 1.0 and 0.36 h in the bloodstream and 3 h versus 1.9 and 0 . 45 h in lung tissues) . The areas under the concentration-time curves (AUCs) in lung tissue for ziracin versus those for ceftriaxone and vancomycin were 36 microg . h/g versus 20 and 9.5 microg . h/g . The prolonged half-life and high AUC for ziracin in tissue contributed to its excellent in vivo activities.

Antimicrob Agents Chemother, 2000 Apr, 44(4), 943 - 9
In vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) against various gram-positive and gram-negative bacteria; van Ogtrop ML et al.; The in vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) were assessed in an experimental murine thigh infection model in neutropenic mice . Mice were infected with one of several strains of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, or Klebsiella pneumoniae . Most infections were treated with a twice-daily dosing schedule, with administration of 0.75 to 192 mg of GAR-936 or WAY 152,288 per kg of body weight . A maximum-effect dose-response model was used to calculate the dose that produced a net bacteriostatic effect over 24 h of therapy . This dose was called the bacteriostatic dose . More extensive dosing studies were performed with S . pneumoniae 1199, E . coli ATCC 25922, and K . pneumoniae ATCC 43816, with doses being given as one, two, four, or eight equal doses over a period of 24 h . The dosing schedules were designed in order to minimize the interrelationship between the various pharmacokinetic and pharmacodynamic parameters studied . These parameters were time above 0.03 to 32 times the MIC, area under the concentration-time curve (AUC), and maximum concentration of drug in serum (C(max)) . The bacteriostatic dose remained essentially the same, irrespective of the dosing frequency, for S . pneumoniae 1199 (0.3 to 0.9 mg/kg/day) . For E . coli ATCC 25922 and K . pneumoniae ATCC 43816, however, more frequent dosing led to lower bacteriostatic doses . Pharmacokinetic studies demonstrated dose-dependent elimination half-lives of 1.05 to 2.34 and 1.65 to 3.36 h and serum protein bindings of 59 and 71% for GAR-936 and WAY 152,288, respectively . GAR-936 and WAY 152,288 were similarly effective against the microorganisms studied, with small differences in maximum effect and 50% effective dose . The glycylcyclines were also similarly effective against tetracycline-sensitive and tetracycline-resistant bacteria . Time above a certain factor (range, 0.5 to 4 times) of the MIC was a better predictor of in vivo efficacy than C(max) or AUC for most organism-drug combinations . The results demonstrate that in order to achieve 80% maximum efficacy, the concentration of unbound drug in serum should be maintained above the MIC for at least 50% of the time for GAR-936 and for at least 75% of the time for WAY 152,288 . The results of these experiments will aid in the rational design of dose-finding studies for these glycylcyclines in humans.

Fetal Diagn Ther, 2000 Mar-Apr, 15(2), 93 - 6
Efficacy and safety of OK-432 sclerotherapy for giant cystic hygroma in a newborn; Samuel M et al.; BACKGROUND: OK-432, a lyophilised incubation mixture of group A Streptococcus pyogenes of human origin, was used as a sclerosant for the involution of a giant cervical cystic hygroma in a newborn . RESULTS: There were no systemic side effects . Blood tests and double immune diffusion tests showed no systemic infection or generalised inflammatory response, or antibody production . Cellular and cytokine-induced localised inflammatory reaction within the cystic hygroma, was observed on analysis of the intracystic fluid . CONCLUSIONS: The leucocytosis induced and activated by OK-432 probably increases the endothelial permeability of the lymphatics . This probably accelerated lymph drainage leading to involution of the cystic hygroma . Intralesional injection of OK-432 was safe and effective therapy for cystic hygroma in this newborn as its inflammatory reaction was localised .

J Infect Dis, 2000 Mar, 181(3), 975 - 83
Genomic differences in Streptococcus pyogenes serotype M3 between recent isolates associated with toxic shock-like syndrome and past clinical isolates; Inagaki Y et al.; Genomic differences among past Streptococcus pyogenes serotype M3 strains isolated in 1973 and before from patients with streptococcal pharyngitis, recent (1990s) serotype M3 clinical isolates from patients with pharyngitis, and recent M3 isolates from patients with toxic shock-like syndrome were investigated by restriction landmark genomic scanning and by modified random-amplified polymorphic DNA-polymerase chain reaction . Similar polymorphic DNA fragments were identified between the older M3 isolates and the recent isolates; also, the recent M3 clinical isolates from patients with pharyngitis were genetically indistinguishable, by the methods used, from the M3 isolates of patients with toxic shock-like syndrome . Although nucleotide sequences of these regions showed no apparent homology with known virulence factors, the DNA fragments could distinguish the recent M3 strains from the past strains . These results suggested that the recent strains have emerged because of genetic divergence.

J Infect Dis, 2000 Mar, 181(3), 966 - 74
Molecular typing of Streptococcus pneumoniae in northeastern Romania: unique clones of S . pneumoniae isolated from children hospitalized for infections and from healthy and human immunodeficiency virus-infected children in the community; Porat N et al.; Microbiologic, serologic, and molecular typing techniques were used to characterize 272 isolates of Streptococcus pneumoniae colonizing or infecting children in Iasi, Romania, during a surveillance study conducted in 1996-1998 . The 574 children in the study were from the following groups: healthy children attending 2 institutions, healthy children hospitalized for elective surgery, hospitalized children with pneumococcal infections, and human immunodeficiency virus (HIV)-infected children in an orphanage . Pneumococci colonizing healthy children from closed communities showed close similarities to pneumococci from children with pneumococcal infections; they expressed a limited number of similar serotypes, showed high frequency of penicillin and multidrug resistance, and shared several common clonal types . In contrast, isolates recovered from healthy children hospitalized for elective surgery expressed a large variety of serotypes, were less frequently resistant to antimicrobial agents, and showed great genetic diversity . Pneumococcal flora colonizing HIV-infected children showed a more complex epidemiology . These observations suggest a possible epidemiologic connection between the flora of S . pneumoniae colonizing healthy children in closed communities and the flora found in children hospitalized for infection.

Drugs, 2000 Jan, 59(1), 7 - 16
Oxazolidinones: a review; Diekema DI et al.; The oxazolidinones represent a novel chemical class of synthetic antimicrobial agents . They exhibit an unique mechanism of protein synthesis inhibition and generally display bacteriostatic activity against many important human pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin- and cephalosporin-resistant Streptococcus pneumoniae . Linezolid, the oxazolidinone which has been selected for clinical development, has near complete oral bioavailability plus favourable pharmacokinetic and toxicity profiles . Results from experimental models of infection and phase II trials reveal linezolid to be highly active in vivo against infections due to many common gram-positive pathogens . The role of linezolid remains to be determined in phase III clinical trials, but it shows great promise as an alternative to glycopeptides and streptogramins to treat serious infections due to resistant gram-positive organisms . Further modification of the oxazolidinone nucleus may yield agents with even greater potency and with novel spectra of activity.

Neurochirurgie, 1999 Dec, 45(5), 417 - 21
{Cervical spine infection with Streptococcus anginosus . Case report}; Fabie F et al.; A case of cervical spine infection due to Streptococcus anginosus is reported . Streptococcus milleri is encountered in the mouth, gastro-intestinal tract, vagina and nasopharynx . It is an uncommon pathogen responsible of suppurative infections such as brain liver or spleen abscesses, intra-abdominal or soft tissue abscesses and pleural empyema . In rare cases it can cause spondylodiscitis and osteomyelitis . Based on the review of eight cases of spondylodiscitis or osteomyelitis, diagnosis and treatment are discussed.

Int J Antimicrob Agents, 2000 Feb, 14(1), 45 - 50
Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms; Blondeau JM et al.; Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin are fluoroquinolones with enhanced Gram-positive activity while retaining broad-spectrum activity against Gram-negative pathogens . Levofloxacin and ciprofloxacin are older quinolones with broad activity against Gram-negative pathogens and borderline activity against some Gram-positive organisms . We compared the in vitro activity of these compounds against 4151 Gram-negative and -positive organisms . Gatifloxacin, grepafloxacin, moxifloxacin and trovafloxacin were highly active against penicillin sensitive and resistant Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus agalactiae . Ciprofloxacin and levofloxacin were active but less potent . All compounds were highly active (overall) against Gram-negative pathogens with ciprofloxacin being the most active agent against Pseudomonas aeruginosa . Our data indicate that the advanced fluoroquinolones will be important compounds for treating infections caused by Gram-positive and Gram-negative pathogens.

EMBO J, 2000 Mar 15, 19(6), 1228 - 40
Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase; Li S et al.; Streptococcus pneumoniae hyaluronate lyase (spnHL) is a pathogenic bacterial spreading factor and cleaves hyaluronan, an important constituent of the extra- cellular matrix of connective tissues, through an enzymatic beta-elimination process, different from the hyaluronan degradation by hydrolases in animals . The mechanism of hyaluronan binding and degradation was proposed based on the 1.56 A resolution crystal structure, substrate modeling and mutagenesis studies on spnHL . Five mutants, R243V, N349A, H399A, Y408F and N580G, were constructed and their activities confirmed our mechanism hypothesis . The important roles of Tyr408, Asn349 and His399 in enzyme catalysis were proposed, explained and confirmed by mutant studies . The remaining weak enzymatic activity of the H399A mutant, the role of the free carboxylate group on the glucuronate residue, the enzymatic behavior on chondroitin and chondroitin sulfate, and the small activity increase in the N580G mutant were explained based on this mechanism . A possible function of the C-terminal beta-sheet domain is to modulate enzyme activity through binding to calcium ions.

J Bacteriol, 2000 Apr, 182(7), 1854 - 63
Capsule biosynthesis and basic metabolism in Streptococcus pneumoniae are linked through the cellular phosphoglucomutase; Hardy GG et al.; Synthesis of the type 3 capsular polysaccharide of Streptococcus pneumoniae requires UDP-glucose (UDP-Glc) and UDP-glucuronic acid (UDP-GlcUA) for production of the {3)-beta-D-GlcUA-(1-->4)-beta-D-Glc-(1-->}(n) polymer . The generation of UDP-Glc proceeds by conversion of Glc-6-P to Glc-1-P to UDP-Glc and is mediated by a phosphoglucomutase (PGM) and a Glc-1-P uridylyltransferase, respectively . Genes encoding both a Glc-1-P uridylyltransferase (cps3U) and a PGM homologue (cps3M) are present in the type 3 capsule locus, but these genes are not essential for capsule production . In this study, we characterized a mutant that produces fourfold less capsule than the type 3 parent . The spontaneous mutation resulting in this phenotype was not contained in the type 3 capsule locus but was instead located in a distant gene (pgm) encoding a second PGM homologue . The function of this gene product as a PGM was demonstrated through enzymatic and complementation studies . Insertional inactivation of pgm reduced capsule production to less than 10% of the parental level . The loss of PGM activity in the insertion mutants also caused growth defects and a strong selection for isolates containing second-site suppressor mutations . These results demonstrate that most of the PGM activity required for type 3 capsule biosynthesis is derived from the cellular PGM.

J Pharm Pharmacol, 2000 Feb, 52(2), 235 - 42
Extract of Juglandaceae regia inhibits growth, in-vitro adherence, acid production and aggregation of Streptococcus mutans; Jagtap AG et al.; Aqueous and alcoholic extracts from Juglandaceae regia, used as chewing sticks to maintain oral hygiene, were tested for their ability to inhibit the growth and some physiological functions of Streptococcus mutans . Both the aqueous and the alcoholic extract strongly inhibited the growth, in-vitro adherence, acid production and glucan-induced aggregation of S . mutans . At a concentration of 8% w/v, the aqueous extract produced a 95% inhibition (P < 0.05) of adherence of S . mutans to glass and a 40% inhibition (P < 0.05) of adherence to tooth surface . The alcoholic extract at a concentration of 10% w/v produced a 95% inhibition (P < 0.05) of adherence of S . mutans to glass and a 56% inhibition (P < 0.05) of adherence to tooth surface . At concentrations of 2% w/v the aqueous and alcoholic extracts significantly inhibited (P < 0.05) glucan-induced aggregation of S . mutans and the in-vitro salivary glycolytic reaction for up to 5 h . Bactericidal effects on S . mutans were also evident . At a concentration of 10% w/v, the zone of inhibition observed with the aqueous extract was 12+/-0.01 mm and that observed with the alcoholic extract was 12.6+/-0.02 mm . As the in-vitro studies had shown that both the aqueous and the alcoholic extract of J . regia, at concentrations of 10% w/v, could inhibit the growth as well as the acid-producing ability of S . mutans, they were tested at the same concentration for their activity in-vivo . Three subjects were employed . Parameters monitored were salivary bacterial count and salivary glycolysis . Mouth-rinsing with the aqueous but not the alcoholic extract significantly reduced total streptococcal counts in the salivary samples obtained up to, and including, 3 h after rinsing, compared with the counts obtained pre-rinsing or after placebo rinsing . Mouth-rinsing with the aqueous extract produced a 65%, 27% and 78% reduction (P < 0.05) in the streptococcal count in the salivary samples obtained 10 min, 1 h and 3 h after rinsing, respectively . Both the aqueous and the alcoholic extract also inhibited the glycolytic reaction by the salivary bacteria for up to 90 min post-rinsing . This study provides evidence to justify the use of J . regia sticks as an aid to maintain oral hygiene.

J Dairy Sci, 2000 Feb, 83(2), 264 - 74
Effects of somatic cell count on quality and shelf-life of pasteurized fluid milk; Ma Y et al.; Milk was collected from eight Holstein cows four times before and four times after intramammary infection with Streptococcus agalactiae . Postinfection milk had significantly higher somatic cell count (SCC) (849,000 cells/ml) than preinfection milk (45,000 cells/ml) . High SCC raw milk had more lipolysis and proteolysis than low SCC raw milk . Pasteurized, homogenized, 2% fat milks from pre- and postinfection periods were stored at 5 degrees C and analyzed for lipolysis, proteolysis, microbial quality, and sensory attributes at 1, 7, 14, and 21 d post processing . During refrigerated storage, the average rates of free fatty acid increase (i.e., lipolysis) and casein hydrolysis in high SCC milk were, respectively, three and two times faster than those in low SCC milk . In general, standard plate counts, coliform counts, and psychrotrophic bacterial counts of both the high and low SCC milks remained low (<100,000 cfu/ ml) during 5 degrees C storage . Low SCC milk maintained high organoleptic quality for the entire 21-d shelf-life period . However, for high SCC milk, between 14 and 21 d, sensory defects were detected, which resulted in low overall quality ratings . The sensory defects mainly included rancidity and bitterness and were consistent with higher levels of lipolysis and proteolysis . Hence, mastitis adversely affected the quality of pasteurized fluid milk . It is recommended that the fluid milk industry consider implementation of premium quality payment programs for low SCC milks.

J Infect, 1999 Nov, 39(3), 171 - 8
Evidence-based medicine: empiric antibiotic therapy in community-acquired pneumonia; Read RC; A number of national society guidelines exist for empiric management of community-acquired pneumonia but these are, to a large extent, not evidence-based, but based on clinical experience, in vitro data, pragmatism and common sense . Many randomized controlled trials of antibiotic therapy in community-acquired pneumonia have been conducted, but most of these have been powered to demonstrate equivalent efficacy of new treatments in comparison with conventional antimicrobial therapy . Development of new antibiotics has been driven by the emergence of penicillin-resistant Streptococcus pneumoniae, but so far there is no hard evidence that beta-lactam therapy fails in community-acquired pneumonia, at least with the higher doses of penicillins that are commonly used in hospital practice . Nonetheless, newer antibiotics have been deployed including macrolides and quinolones, and have demonstrated equivalent (and in some cases, marginally improved) efficacy to older antibiotic treatments in randomized control trials . A number of studies have shown that it is possible to stratify patients according to severity of illness, to in-patient or out-patient management protocols . These have been validated and refined.

Am J Vet Res, 2000 Mar, 61(3), 275 - 9
Effects of lactoferrin and milk on adherence of Streptococcus uberis to bovine mammary epithelial cells; Fang W et al.; OBJECTIVE: To determine whether lactoferrin (LF) or milk influenced adherence of Streptococcus uberis to bovine mammary epithelial cells . SAMPLE POPULATION: Three strains of S uberis from cows with mastitis, pooled milk samples from 3 clinically healthy Jersey cows early in the lactation period, and bovine mammary epithelial cells from a clonal cell line . PROCEDURES: Adherence of S uberis to bovine mammary epithelial cells in the presence of various concentrations of LF or milk and after pretreatment of bacteria with LF or milk was tested . Bacteria were cultured with mammary epithelial cell monolayers for 1 hour . The culture supernatant was removed, and the epithelial cells were lysed . Adherence index was calculated as number of colony-forming units (CFU) in the cell lysate divided by number of CFU in the supernatant times 10,000 . RESULTS: All 3 strains of S uberis were found to bind to purified LF and LF in milk . Addition of LF to the culture medium enhanced adherence of all 3 strains to mammary epithelial cells, whereas addition of milk enhanced adherence of 2 strains and decreased adherence of the third . Pretreatment of bacteria with LF or milk increased adherence of 1 of the strains but decreased adherence of the other 2 . Increased adherence was antagonized by rabbit antibovine LF antibody . CONCLUSIONS: Results suggest that LF may function as a bridging molecule between S uberis and bovine mammary epithelial cells, facilitating adherence of the bacteria to the cells.

FEMS Microbiol Lett, 2000 Mar 15, 184(2), 149 - 53
Protein interactions of SGP, an essential Streptococcus mutans GTPase, revealed by biochemical and yeast two-hybrid system analyses; Baev D et al.; SGP, a Streptococcus mutans essential GTPase, plays a role in the stress response of the organism . Recently, we proposed that one of the physiological functions of the SGP is the modulation of the GTP/GDP ratio under different growth conditions . In order to further determine the functions of SGP and its possible interactions with other molecules, we carried out immunoprecipitation, SGP binding, and the yeast two-hybrid system analyses . These approaches suggest that SGP may oligomerize and such interactions could be important for the function of this regulatory protein.

J Cataract Refract Surg, 2000 Mar, 26(3), 460 - 1
Pneumococcal keratitis after laser in situ keratomileusis; Dada T et al.; A 20-year-old man developed keratitis in his right eye 2 days after laser in situ keratomileusis (LASIK) . The patient had rubbed the eye with unclean fingers the night before the onset of symptoms . Examination showed an inferior corneal ulcer with dense infiltration at the junction of the lamellar flap and the surrounding cornea associated with a hypopyon . Streptococcus pneumoniae was isolated on culture . The ulcer resolved with combination therapy of cephazolin 5% and tobramycin 1.3% eyedrops . Patients having LASIK should be instructed that inadequate patient hygiene may predispose to bacterial keratitisPublication Types:

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