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Vitamin B6-dependent Streptococcus mitior (mitis) isolated from patients with systemic infections.

Strains of nutritional-variant viridans Streptococcus were isolated from two patients with bacterial endocarditis and from one patient with a pancreatic abscess. All three strains grew as satellite colonies of other bacteria but did not grow as pure cultures in media lacking sufficient thiol compounds. For one-half maximal growth these organisms required the addition of one of the active forms of the B6 vitamin, pyridoxal with HCl (0.16-1.45 mug/ml) or pyridoxamine dihydrochloride (0.67-2.0 mug/ml), or addition of l-cysteine (0.235-0.425 mg/ml) to routine bacteriological media. The active forms of vitamin B6 are essential coenzymes in the synthesis of l-cysteine and of other thiol compounds. Use of media supplemented with 0.001 percent pyridoxal with HCL led to identification of the strains as Streptococcus mitior (mitis). Incorporation of pyridoxal with HCl, pyridoxamine dihydrochloride, or l-cysteine into media is recommended for the isolation and identification of vitamin B6-dependent viridans streptococci.

Abscess↗

Rectal colonization with group B streptococcus: relation to vaginal colonization of pregnant women.

Anorectal carriage as a possible primary source of vaginal colonization by group B Streptococcus was investigated. The study was performed during two separate periods and included 789 pregnant women and 422 neonates. Specimens from multiple sites were obtained for culture from all women and infants and were streaked onto blood agar plates containing 8 mug of gentamicin sulfate/ml and 15 mug of nalidixic acid/ml, which allow selective growth of streptococci. Cultures positive for group B streptococci were obtained from 162 (20.5%) of the pregnant women and from 50 (11.8%) of the neonates. Rectal cultures were positive for streptococci in 142 (17.9%) of the women, and vaginal cultures gave positive results in 81 (10.2%). The higher incidence of positive results in rectal as opposed to vaginal cultures (ratio of 2:1) was encountered during all phases of the study. This finding suggests that the gastrointestinal tract may be the primary site of colonization by group B Streptococcus and that vaginal colonization may represent contamination from this source.

Culture Media↗

Specific proteolysis of human IgA by Streptococcus pneumoniae and Haemophilus influenzae.

Streptococcus pneumoniae and Haemophilus influenzae are among the most common bacterial pathogens responsible for respiratory tract infections in otherwise healthy humans. Thirty-six strains of S. pneumoniae, 62 strains of H. influenzae, six hospital-acquired respiratory pathogens, and a strain of Streptococcus pyogenes were examined for production of IgA protease, a bacterial enzyme whose only known substrate is human IgA1. IgA protease was produced by 100% of the isolates of S. pneumoniae and 98% of the isolates of H. influenzae. The enzyme from both species cleaved human serum and secretory IgA1 proteins, but not human IgA2, IgG, or human serum albumin. None of the hospital-acquired pathogens had detectable IgA protease activity, a finding indicating that the production of this enzyme distinguishes S. pneumoniae and H. influenzae from the opporunistic respiratory pathogens.

Antibodies, Bacterial↗

Molecular epidemiology of group A streptococcus M type 1 infections.

Data were reviewed about 665 streptococcus M type 1 isolates received by the Streptococcus Reference Laboratory of the New Zealand Communicable Disease Centre between 1980 and 1991. Isolates were voluntarily submitted by diagnostic laboratories throughout New Zealand as part of a surveillance system for streptococcal infections. Over the study period, distribution of M type 1 was uneven, and two waves of infections occurred, each with a distinctive disease pattern. Molecular typing using restriction fragment length polymorphism (RFLP) analysis was used to examine phylogenetic relationships among isolates randomly selected from different geographic locations for each of the years studied. Although six distinct RFLP patterns occurred, most isolates (74%), including those of both waves, belonged to type 1a. This type and one other were also identified among additional isolates originating from Australia and the United States. Typed isolates from cases of severe invasive disease occurring both in the United States and in New Zealand in the late 1980s belonged to RFLP type 1a.

Humans↗

Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniae in a murine sepsis model.

Trovafloxacin is a new fluoroquinolone that has potent microbiological activity against the pneumococcus, including penicillin-resistant strains. To evaluate the protective effect of trovafloxacin, ciprofloxacin and ampicillin against penicillin-susceptible, -intermediate and -resistant strains of Streptococcus pneumoniae, an intraperitoneal, immunocompetent mouse model of sepsis was used. The minimum lethal dose (MLD) for each isolate was determined in duplicate. A single sc dose of each antibiotic was administered over a wide range of doses 1 h after the ip inoculation of the test isolate at the MLD. The assessment of the protective dose for 50% of the population (PD50) for each antimicrobial/bacteria combination was performed in triplicate and the PD50 value was calculated at the end of 5 days. Results showed that trovafloxacin provided PD50 values that were significantly lower than those of ciprofloxacin for all isolates. For the penicillin-susceptible and -intermediate isolates, the PD50 values of ampicillin were significantly lower than those for either of the fluoroquinolones studied; however, trovafloxacin was statistically superior to both ciprofloxacin and ampicillin against the penicillin-resistant strain. Therefore, regardless of penicillin susceptibility, trovafloxacin has potent activity against Streptococcus pneumoniae and may be a viable alternative for the treatment of penicillin-resistant isolates.

Ampicillin↗

In vitro selection of resistance to clindamycin related to alterations in the attenuator of the erm(TR) gene of Streptococcus pyogenes UCN1 inducibly resistant to erythromycin.

A clinical isolate of Streptococcus pyogenes UCN1 intermediate to erythromycin (MIC 1 mg/L) and susceptible to clindamycin (MIC 0.03 mg/L) harboured an inducible erm(TR) gene encoding a ribosomal methylase. We have selected in vitro, in the presence of concentrations of clindamycin ranging from 0.12 to 1 mg/L, one-step mutants that are highly resistant to this antibiotic (MIC 64 mg/L) at a frequency of 10(-7). By contrast, in an erythromycin-susceptible strain of S. pyogenes UCN5, mutants could be selected only by a low concentration of clindamycin (0.12 mg/L) at a frequency of 10(-9). Clindamycin resistance in four of six S. pyogenes UCN1 mutants was associated with deletions of 163 and 6 bp, as well as a tandem duplication of 101 bp in the regulatory sequence of the erm(TR) gene. The role of these structural alterations in clindamycin resistance was demonstrated by cloning the erm(TR) gene from the wild-type and mutant strains in Escherichia coli DB10, a mutant susceptible to macrolides. Clindamycin resistance was expressed only when the erm(TR) gene was preceded by an altered attenuator. Mutations could lead to the formation of mRNA secondary structures accounting for the accessibility of the ribosome-binding site and the initiation codon of the ErmTR methylase to the ribosomes, and subsequently for the translation of the erm(TR) transcripts. The easy selection in one step of mutants resistant to high levels of clindamycin by concentrations of this antibiotic ranging from four to 40 times the MIC leads us to recommend caution in the use of clindamycin therapy in group A Streptococcus infections.

Anti-Bacterial Agents↗

Comparative activity of garenoxacin and other agents by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens.

OBJECTIVES: Garenoxacin is a novel des-F(6)quinolone that has shown excellent antimicrobial activity against a wide range of clinically important microorganisms. In this study, its activity was examined, in comparison with that of other antimicrobial agents, by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens. METHODS: Overall, 200 bacterial strains were tested. The antimicrobial activity of garenoxacin was compared with that of ciprofloxacin, levofloxacin, moxifloxacin, amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone, imipenem, erythromycin and clarithromycin. In addition, the bactericidal activity of garenoxacin, moxifloxacin, levofloxacin and ciprofloxacin was evaluated by time-kill analysis against four strains each of staphylococci [two methicillin-susceptible (MSSA) and two methicillin-resistant (MRSA)], pneumococci (two penicillin-susceptible and two penicillin-resistant) and Streptococcus pyogenes (two erythromycin-susceptible and two erythromycin-resistant). Antibiotics were tested at concentrations 1-8 x MIC. RESULTS: MIC90 values of garenoxacin for the MSSA and MRSA strains were 0.03 and 2 mg/L, respectively. Among all the quinolones tested, garenoxacin yielded the lowest MIC values against all pneumococci (MIC90 0.12 mg/L) irrespective of macrolide resistance; the rank order of activity was garenoxacin> moxifloxacin>levofloxacin>ciprofloxacin. Excellent activity was shown also against Haemophilus influenzae (MIC90 or= 3 log10 decrease in viable counts (cfu/mL) within 3 h at 4 x MIC, whereas a moderate, slower killing rate was observed versus streptococci. CONCLUSIONS: This investigational des-F(6)quinolone represents a promising alternative for the treatment of respiratory tract infections.

Anti-Infective Agents↗

The glycopeptide vancomycin does not enhance toll-like receptor 2 (TLR2) activation by Streptococcus pneumoniae.

OBJECTIVES: The exposure of Streptococcus pneumoniae to cell-wall-active antibiotics in vivo and in vitro results in the release of bacterial components that can induce proinflammatory activation of human cells via toll-like receptor 2 (TLR2). The aim of this study was to compare the activation of human TLR2 pathways after exposure of S. pneumoniae to faropenem, cefotaxime and vancomycin. MATERIALS AND METHODS: Streptococcus pneumoniae D39 was exposed to cefotaxime, faropenem or vancomycin for 6 h during lag or early log phase growth. IL-8 promoter activity of HeLa cells was measured using a dual luciferase reporter plasmid system. HeLa cells were transfected with an expression vector containing TLR2/CD14, or empty vector/CD14 and IL-8 promoter activity was measured using luminescence. Cells were stimulated with antibiotic-treated bacteria, untreated bacteria or medium-only controls. RESULTS: Lag phase S. pneumoniae treated at sub-MIC (1/8 MIC) cefotaxime or faropenem induced 11-fold and 8-fold increases, respectively, in TLR2-mediated IL-8 promoter activity when compared with untreated bacteria. Early log MIC cefotaxime or faropenem-treated bacteria also enhanced TLR2 activation by 3-fold and 4-fold, respectively, when compared with untreated bacteria. Vancomycin treatment had no effect on TLR2 induction at any growth stage or MIC ratio tested. CONCLUSIONS: beta-Lactam antibiotics induce surface changes and release of cell wall structures from bacteria that are proinflammatory via TLR2, but the glycopeptide vancomycin does not.

Anti-Bacterial Agents↗

In vitro antimicrobial activity of benzalkonium chloride against clinical isolates of Streptococcus agalactiae.

OBJECTIVES: Despite antibiotic prophylaxis for at-risk mothers during labour and delivery, Streptococcus agalactiae (group B Streptococcus; GBS) still causes substantial morbidity and mortality among newborns. In addition to the well-known side effects of the administration of antibiotics, resistance to drugs recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased, thus raising concern about the possibility of inadequate prophylaxis. On this basis we evaluated the antimicrobial activity of benzalkonium chloride against GBS, which has been described as an antimicrobial agent for the topical treatment of vaginal infections. METHODS: A total of 52 GBS from pregnant women have been studied. The capacity of benzalkonium chloride as well as of penicillin, erythromycin, clindamycin, vancomycin, chloramphenicol and tetracycline to inhibit GBS was evaluated using broth macrodilution and microdilution methods, respectively. RESULTS: While all the strains were penicillin- and vancomycin-susceptible, 19.2% were resistant to both erythromycin and clindamycin. In contrast, all GBS isolates were either inhibited or killed by benzalkonium chloride at not only low but also very similar concentrations (MIC90 = 3.12 mg/L). CONCLUSIONS: Benzalkonium chloride might represent an alternative strategy that is useful in reducing vaginal GBS colonization in pregnant women before delivery by topical treatment.

Anti-Infective Agents, Local↗

Efficacy and safety of twice-daily pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg) in the treatment of adults with community-acquired pneumonia in a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.

OBJECTIVES: This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae. PATIENTS AND METHODS: Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192). RESULTS: Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain). CONCLUSIONS: Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.

Adult↗

Effect of MUC7 peptides on the growth of bacteria and on Streptococcus mutans biofilm.

OBJECTIVES: To investigate the susceptibility of selected bacteria as well as Streptococcus mutans biofilm to MUC7 peptides and compare the activities with those of other known antimicrobial peptides. METHODS: MIC and MBC of peptides for S. mutans, Escherichia coli, Streptococcus gordonii, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Pseudomonas aeruginosa were determined using the microdilution method. For S. mutans, the effects of the peptides on the kinetics of growth inhibition, time-killing, and on biofilm formation and reduction were also examined. For biofilm studies, polystyrene microtitre plates, Calgary Biofilm Device (CBD) and hydroxylapatite (HA) discs, along with Crystal Violet and Alamar Blue dyes, and/or EM observations, were employed. RESULTS: S. mutans was the most susceptible to all peptides tested (MICs of 9.4-25.0 microM), compared with the other species (MICs of 3.1->100 microM). MUC7 peptides (except MUC7-12-mer-L4) exerted 2-fold higher activity against S. mutans than Hsn5-12-mer and magainin-II, and faster killing of S. mutans than Hsn5-12-mer. The MUC7 peptides also had an effect on S. mutans biofilm. On the polystyrene plates, they suppressed the biofilm formation, with MBIC(50) of 6.25-12.5 microM, and reduced the 1 day developed biofilm in a batch culture, with MBRC(50) of 25-50 microM. On the CBD pegs, the viabilities of the biofilm were suppressed by >95% in the presence of MUC7 peptides at 4x MIC (50 microM). One day developed biofilm viabilities were inhibited by 49-75%. On HA, the formation of biofilm (as observed by EM) was also considerably reduced. CONCLUSIONS: MUC7 peptides present somewhat preferential antimicrobial activity against S. mutans. They also have an effect on in vitro formation and reduction of the preformed S. mutans biofilm.

Anti-Bacterial Agents↗

Type-specific immunity and pharyngeal acquisition of group A Streptococcus.

A prospective study of spread of M-type 1, 2, 13, 14, 25 and 60 group A Streptococcus in 64 families in Qalyub, Egypt, in 1972-1974 showed that type-specific serum bactericidal antibody does not protect against pharyngeal acquisition of homologous organisms. The presence of type-specific antibody also does not appear to affect duration of carriage of the organism. Type-specific immunity must be mediated in another way, such as by local antibody or trough prevention of infection (as evidenced by a host response) following acquisition. This study also confirms the observations of others that administration of penicillin lowers the probability that a person who acquires group A Streptococcus will develop type-specific antibody.

Antibodies, Bacterial↗

Infective endocarditis due to Streptococcus bovis. A report of 53 cases.

Fifty-three patients (42 men; 11 women) with Streptococcus bovis infective endocarditis attended a tertiary cardiology hospital between 1980 and 1991, and constituted 11% of the total number of infective endocarditis cases hospitalized there during that period. The mean age was 59 +/- 15 years; 15 had previously suffered valvular disease (12) or had a valvular prosthesis (3); one patient had had a previous infective endocarditis. The infective episode involved the aortic valve in 26 patients, both the aortic and mitral valves in 18 patients, the mitral valve only in six and other valves in three. Echocardiographic examination showed one or more vegetations in 44 patients. Cardiac failure was diagnosed in 35 patients and embolic episodes in 22, of whom 11 were cerebrovascular accidents. The patients became afebrile 19 +/- 39 days after starting antibiotic treatment. Valve replacement was performed in 37 patients during their initial hospitalization, and in four during follow-up. After a mean follow-up of 4.6 +/- 3.1 years with a 100% follow-up, 15 patients died: 1 preoperatively, one in the first 30 days after operation, 13 later (8141 operated patients and 5/12 non-operated patients). Actuarial survival was 73% at 5 years. Gastrointestinal signs were present in 12 patients; 43 patients (81%) had a full colonic examination which showed polyps in 20 patients and adenocarcinomas in seven. Of 11 late deaths four were related to a malignant colonic tumour. This study confirms that Streptococcus bövis infective endocarditis is 'relatively benign', but it stresses the frequency and potential severity of the associated colonic lesions, requiring colonoscopy and making the treatment of high risk lesions mandatory.

Adenocarcinoma↗

Molecular characterization of a novel beta1,3-galactosyltransferase for capsular polysaccharide synthesis by Streptococcus agalactiae type Ib.

A group B streptococcus, Streptococcus agalactiae type Ib, produces a high-molecular-weight polysaccharide consisting of the following pentasaccharide repeating unit: -->4)-[alpha-D-NeupNAc-(2-->3)-beta-D-Galp-(1-->3)-beta-D-GlcpNAc-(1-->3)]-beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->. The type-specific capsular polysaccharide (CP) synthesis (cps) genes of this strain were cloned and analyzed. A cloned 10-kb DNA fragment contained cpsIbE to L and neu (neuraminic acid synthesis gene) B. Comparison of the gene products with those of S. agalactiae type Ia, which has a similar but distinct CP, showed that the translation products of cpsIa and cpsIb genes exhibited very high homology except for those of cpsJ and K. In the type Ia strain, cpsIaJ encodes beta1,4-galactosyltransferase, which catalyzes the transfer of galactose as the fourth monosaccharide of the sugar repeating unit. In the type Ib CP, this galactose forms a beta1,3-linkage to GlcNAc. The low homology between the type Ia and Ib CpsJs seems to reflect this difference. By enzymatic activity measurement, the cpsIbJ product was found to display beta1,3-galactosyltransferase activity. Furthermore, hydrophobic cluster analysis clarified the similarities and differences of the structures in N-terminal regions, including the DXD motif, between the galactosyltransferases.

Amino Acid Sequence↗

Effects of alcohols on the hydrolysis of colominic acid catalyzed by Streptococcus neuraminidase.

Regulation of the activity of neuraminidase of Streptococcus sp. (group K) was evaluated by examining the effects of alcohols on the hydrolysis of colominic acids catalyzed by the neuraminidase. Two kinds of alcohol binding site, activation and inhibition sites, were proposed to exist. Competitive inhibition was observed with alcohols smaller than polyethylene glycol #300 (average molecular weight: 300), so the inhibition site is considered to be the substrate binding site, the size of which was estimated to be 10 A in diameter. On the contrary, polyethylene glycols larger than this size activated the enzyme by 1.5-1.8 times. The activity could be raised by binding of the polyethylene glycols to the activation site. This activation was shown to be due solely to the decrease in the Michaelis constant, Km. The smaller polyethylene glycols (#200 and #300) were also considered to bind to the activation site, although activation was not clearly observed due to compensation with inhibition. Strong substrate inhibition by colominic acid was also observed. The activity of Streptococcus neuraminidase was shown to be regulated intricately by the substrate colominic acid and alcohols contained in the reaction medium.

Alcohols↗

Case report: prosthetic valve endocarditis due to a nutritionally variant streptococcus.

The first report of prosthetic valve endocarditis due to a nutritionally variant streptococcus is presented. A 21-year-old woman developed persistent fever within one week of mitral valve replacement. Prosthetic valve dysfunction developed necessitating valve replacement. Cultures of blood and the excised prosthetic valve using routine media were negative; Streptococcus mitior grew as satellite colonies around Staphylococcus aureus and in beef heart infusion broth supplemented with 0.001% pyridoxine HCl. Treatment with penicillin G and streptomycin for six weeks was curative. Nutritionally variant streptococci should be considered in patients with prosthetic valve endocarditis and negative routine cultures.

Adolescent↗

Colonization of hydrogel lenses with Streptococcus pneumoniae: risk of development of corneal infiltrates.

PURPOSE: To report the association between colonization of contact lenses with Streptococcus pneumoniae and the observation of corneal infiltrative events in a group of patients wearing disposable hydrogel lenses on an extended-wear schedule. METHODS: In a prospective clinical trial, 330 patients wore disposable hydrogels on a 6-night extended-wear and replacement schedule. The contact lens, lid, and conjunctival microbiota of these subjects was analyzed at frequent intervals and at the time of an adverse event. RESULTS: Streptococcus pneumoniae was an uncommon isolate and was recovered from only one of the 3,763 conjunctival samples, five (0.1%) of the 3,764 lid samples, and 33 (0.8%) of the 4,315 contact lens samples. Of the 33 lens samples, 10 (30%) were associated with corneal infiltrative events. Many of the events were mild inflammatory responses and resolved rapidly on discontinuation of lens wear. The presence of S. pneumoniae on the contact lens was associated with a significant risk of development of corneal infiltrates (odds ratio, 3.0; p = 0.0227, logistic-regression analysis). CONCLUSIONS: Presence of S. pneumoniae on hydrogel lenses is a significant risk factor for the development of corneal infiltrates.

Adolescent↗

The incidence of group B beta hemolytic streptococcus in antepartum urinary tract infections.

Group B beta hemolytic streptococcus (GBBHS) is a potential pathogen for the urinary tract during pregnancy. At this medical center, 19 of 371 patients with urinary tract infection (5.1%) presented with Group B beta hemolytic streptococcus as the proven causative microorganism. This microorganism should not be considered only as a contaminant when isolated by urine culture.

Adolescent↗