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Successful ceftriaxone therapy of endocarditis due to penicillin non-susceptible viridans streptococci.

Viridans streptococci are a major cause of infective endocarditis, and penicillin non-susceptibility is increasing in these organisms. We present the initial reported case of infective endocarditis due to penicillin non-susceptible viridans streptococci successfully treated with ceftriaxone monotherapy. The lack of evidence supporting the recommendations for treatment of endocarditis due to penicillin non-susceptible viridans streptococci is discussed.

Anti-Bacterial Agents↗

Synergism with aminoglycosides of penicillin, ampicillin and vancomycin against non-enterococcal group-D streptococci and viridans streptococci.

The antibiotic susceptibility of 10 strains of non-enterococcal group-D streptococci was compared with that of 20 strains of viridans streptococci. The minimal inhibitory concentrations of penicillin, ampicillin, oxacillin, nafcillin, cephalothin, vancomycin, erythromycin and clindamycin for the two groups of streptococci were very similar in range and median values. Both groups of streptococci were resistant to the aminoglycosides. The effect of the combination of penicillin, ampicillin or vancomycin with streptomycin, kanamycin, gentamicin or tobramycin on the in-vitro killing of the two groups of streptococci was compared. For all the antibiotic combinations tested, synergism was demonstrated against all strains of non-enterococcal group-D streptococci after one or more of the time-intervals 6, 24 and 48 h. Some or all of the antibiotic combinations were synergistic against all strains of viridans streptococci after one or more of the same time-intervals. The other aminoglycosides (kanamycin, gentamicin and tobramycin) offered no advantage over streptomycin in synergism with penicillin, ampicillin or vancomycin against nonenterococcal group-D streptococci or viridans streptococci. These results suggest that non-enterococcal group-D streptococcal endocarditis may be treated by the same regimen as endocarditis caused by the viridans streptococci.

Aminoglycosides↗

Proinflammatory cytokine production by human peripheral blood mononuclear cells stimulated with cell-free supernatants of Viridans streptococci.

Viridans streptococci (VS) have become recognized as an increasingly important cause of bacteraemia in neutropenic patients undergoing chemotherapy. Surprisingly, VS bacteraemia is associated with toxic shock-like syndrome (TSLS) and adult respiratory distress syndrome (ARDS), features not seen in non-neutropenic patients with viridans streptococcal bacteraemia. The mechanism by which these Gram-positive bacteria cause hypo-tension in the absence of endotoxin is not known. In this study, we have analysed the ability of cell-free bacterial supernatants derived from VS to induce the production of a number of cytokines from human peripheral blood mononuclear cells (PBMC). These cytokines were tumour necrosis factor alpha (TNF-alpha), tumour necrosis factor beta (TNF-beta) and interleukin 8 (IL-8). All 59 strains were able to induce these proinflammatory cytokines. We conclude that VS do produce secreted products which are able to stimulate the production of cytokines which may be important in the pathogenesis of shock caused by these bacteria.

Cell-Free System↗

Resistance to penicillin-streptomycin synergy among clinical isolates of viridans streptococci.

Viridans streptococci are thought to be highly susceptible to penicillin and streptomycin. We recently encountered a unique group of 15 isolates from South Africa epidemiologically related to the isolation of penicillin-resistant pneumococci. These organisms were highly resistant to penicillin (PCN) (minimal inhibitory concentration, 1 to 32 micrograms/ml) and streptomycin (SM) (minimal inhibitory concentration, greater than or equal to 2,000 micrograms/ml). Two additional organisms with high-level streptomycin resistance were identified when 168 clinical isolates from Boston were screened. Time-kill studies with four organisms resistant to high levels of SM demonstrated lack of synergy between PCN and SM but marked synergy between PCN and gentamicin. Adenylylating, acetylating, and phosphorylating activity could not be detected in three organisms studied, and novobiocin failed to cure the SM resistance. Protein synthesis by ribosomes isolated from these organisms was dramatically reduced in the presence of gentamicin but was relatively resistant to inhibition by SM.

Bacterial Proteins↗

Comparison of API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI to conventional biochemical tests for identification of viridans streptococci.

Viridans group streptococci (36 stock strains and 167 single patient blood culture isolates) were assessed using API Rapid Strep, Baxter MicroScan Rapid Pos ID Panel, BBL Minitek Differential Identification System, IDS RapID STR System, and Vitek GPI methods. Identification data obtained with these systems were compared with those indicated by conventional biochemical procedures. API, Baxter MicroScan, BBL, IDS, and Vitek corresponded with conventional biochemical identification in 74%, 66%, 65%, 50%, and 61% of the isolates, respectively; using recommended supplemental tests, agreement was augmented in 9%, 11%, 20%, 11%, and 21% of the isolates, respectively. Disagreement with conventional biochemical methods occurred in 14%, 17%, 14%, 32%, and 10% of the commercial techniques, respectively; no identification was possible in 2%, 5%, fewer than 1%, 6%, and 8% of specimens, respectively. BBL, API, and Baxter MicroScan systems provided the most reliable rapid identification, although supplemental testing often was required. Until a higher percentage of correct identification data can be obtained without supplemental procedures, conventional biochemical techniques will remain the methods of choice for identification of viridans streptococci.

Bacteriological Techniques↗

Stimulation of cytokine release and adhesion molecule expression by products of Viridans streptococci.

The viridans streptococci (VS) are associated with the development of a rapidly fulminant shock syndrome in neutropenic patients. A panel of 52 VS strains isolated from the blood of neutropenic patients was used to demonstrate the ability of culture supernatants and cell walls of VS to induce release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 from whole blood in a dose- and strain-dependent fashion. Intercellular adhesion molecule-1 was shown to be markedly up-regulated on endothelial cells after incubation with plasma from blood exposed to cell walls or culture supernatants. This up-regulation was blocked by IL-1 receptor antagonist but not neutralizing antibody against TNF-alpha. These data may help explain the pathogenesis of the viridans streptococcal shock syndrome in neutropenic patients.

Bacteremia↗

Genetic transformation in Streptococcus sanguis. Identification, surface spreading and competence of invasive strains of Streptococcus sanguis Lancefield groups H and W and other invasive viridans streptococci.

Of 46 viridans streptococci isolated from cases of probably true bacteremia, 26 strains or 56% could be grouped serologically in the Lancefield system. Eight strains (17%) were identified as serogroup H (characteristic of Streptococcus sanguis), ten strains (22%) as serogroup W (a new group antigen found in S. sanguis) and eight strains (17%) as serogroup K (related to S. mitis (mitior)). The high number of serogroupable viridans streptococci was specially due to the introduction of serogroup W and indicates the importance of this serogroup in cases of bacteremia. A set of six diagnostic tests (production of hydrogen peroxide, arginine and esculin hydrolysis, polysaccharide production, Voges-Proskauer reaction, mannitol fermentation) was used for speciation of the viridans streptococci; in addition, search for spreading zones around the colonies was included in the diagnostic procedure. Spreading zones were only present in S. sanguis and occurred more frequently in group H strains than group W strains. The 46 viridans streptococci were tested in genetic transformation. The prevalence of spontaneous competence in strains isolated from the blood was high, particularly in S. sanguis serogroup H (88%) and W (50%). For serogroup H, spontaneous competence was found as frequently among invasive strains as among carrier isolates previously studied.

Antigens, Bacterial↗

Viridans streptococci in blood cultures. Can we see any patterns of species related to patient category? Review of 229 cases of positive cultures with viridans streptococci.

We present a review of 229 blood cultures with viridans streptococci collected during a period of eight and a half years from 1986 to 1994 at a teaching hospital in Sweden. The clinical significance of the growth of viridans streptococci is always uncertain, since these bacteria can be contaminants from the skin flora. Growth in more than one culture bottle strengthens the clinical value of the finding. The question was whether species identification might also help in the assessment of the clinical relevance of the finding. The results show that Streptococcus mitis occurs significantly more frequently in blood cultures from the departments dealing with cancer patients. Even with polymicrobial growth in blood cultures, S. mitis should be considered a pathogen of clinical relevance, not a contaminant.

Blood↗

Secretory IgA, salivary peroxidase, and catalase-mediated microbicidal activity during hydrogen peroxide catabolism in viridans streptococci: pathogen coaggregation.

Viridans streptococci can kill methicillin-resistant Staphylococcus aureus (MRSA) through the production of hydrogen peroxide (H2O2). However, several hundred viridans streptococci cells are necessary to kill 1 cfu of MRSA. We analyzed the potency of bactericidal and fungicidal effector molecules induced by catabolism of H2O2 in the oral cavity. Secretory IgA (SIgA) and an unidentified salivary component bound Streptococcus sanguinis, a viridans streprococcus, and MRSA into coaggregates. In these coaggregates, salivary peroxidase and the MRSA catalase produced singlet molecular oxygen (1O2) from H2O2 produced by viridans streptococci. SIgA converted 1O2 into ozone, which has potent bactericidal and fungicidal activity. We calculated that <10 cfu of Streptococcus sanguinis were necessary to kill 1 cfu of MRSA in the coaggregate. SIgA, Aspergillus niger catalase, and H2O2 in saliva killed Candida albicans, which is highly resistant to reagent H2O2. Together with indigenous bacteria and innate immunity, SIgA potentially constitutes a novel system that may sustain oral homeostasis.

Adult↗

Cell surface hydrophobicity of group D and viridans streptococci isolated from patients with septicaemia.

Sixty-three strains of Group D streptococci and viridans streptococci isolated from blood cultures during a two year period were typed to the species level with conventional biochemical tests and API Strep. Streptococcus faecalis was the most common species isolated followed by S. sanguis, S. mitis and S. constellatus (S. milleri). One of the two isolates of S. faecium was a contamination. The reported increasing frequency of this organism and other Group D and viridans streptococci as well as the association of S. bovis with malignant bowel disease indicate the need for full identification of streptococcal isolates from blood cultures. Pronounced surface hydrophobicity as measured with the salt aggregation test (SAT) was expressed by 59/63 (94%) of the blood culture isolates whereas strains isolated from commercial fermentation products and strains passaged several times were hydrophilic. In the presence of human serum albumin which binds to lipoteichoic acid only one strain decreased in surface hydrophobicity. The surface hydrophobicity of two strains even slightly increased indicating that lipoteichoic acid but marginally contributes to surface hydrophobicity of streptococcal cells from these species.

Adolescent↗

Utilization of sialic acid by viridans streptococci.

The importance of viridans streptococci as agents of serious extra-oral diseases, including endocarditis, is now recognized. We have tested the hypothesis that the ability to utilize sialic acid as a nutrient source may play a role in the proliferation of these organisms. The type strains of the 15 presently recognized species of viridans streptococci and two clinical isolates-S. oralis (AR3), isolated from a patient with infective endocarditis, and S. intermedius (UNS35), a brain abscess isolate-were studied for their ability to utilize sialic acid. Only S. oralis, S. sanguis, S. gordonii, S. mitis ("oralis group") S. intermedius, S. anginosus, S. constellatus ("milleri group"), and S. defectivus ("nutritionally variant group") were able to use sialic acid (N-acetylneuraminic acid) efficiently as a sole carbon source. Formate, acetate, and ethanol were produced as the major metabolic end-products of sialic acid metabolism, while corresponding glucose-grown cultures produced lactate as the major metabolic end-product. Utilization of sialic acid was independent of the production of sialidase. Cell-free extracts of sialic acid-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (NPL; the first enzyme in the intracellular catabolism of sialic acid) and N-acetylglucosamine-6-phosphate (GlcNAc-6-P) deacetylase and glucosamine-6-phosphate (GlcN-6-P) deaminase (enzymes involved in the intracellular catabolism of N-acetylglucosamine). These activities were repressed by growth in the presence of glucose. The intracellular fate of sialic acid, after cleavage by NPL into N-acetylmannosamine (ManNAc) and pyruvate, is uncertain, but the elevated levels of GlcNAc-6-P deacetylase and GlcN-6-P deaminase in sialic acid-grown cells suggest that phosphorylation and isomerization are possible steps in the metabolism of ManNAc to generate an intermediate common to the pathway of N-acetylglucosamine metabolism. The species of viridans streptococci that have the ability to utilize sialic acid are those most commonly associated with extra-oral diseases, and this ability is likely to play a role in the persistence and survival of these infecting organisms in vivo.

Acetylglucosamine↗

In vitro activity of telithromycin against mefA and ermB erythromycin-resistant viridans streptococci isolated from bacteremia of oral origin in Spain.

Erythromycin-resistant viridans streptococci are often responsible of bacteremias following dental manipulations. The aim of this study was to evaluate the in vitro activity of telithromycin against erythromycin-susceptible and erythromycin-resistant viridans streptococci. Venous blood samples were collected from 84 patients, 30 s after dental extractions. Viridans streptococci were identified by conventional microbiological techniques. A set of 36 viridans streptococci were selected to investigate the in vitro activity of telithromycin by the agar dilution method. Macrolide resistance genes were amplified with specific primers for the mefA and ermB genes and visualized by electrophoresis. For erythromycin-susceptible viridans streptococci, telithromycin minimal inhibitory concentration90 (MIC90) was <0.008 microg/ml. For erythromycin-resistant viridans streptococci, telithromycin MIC90 was 1 microg/ml. The MIC90 to telithromycin of the mefA-positive and ermB-negative viridans streptococci was lower than that of the mefA-negative and ermB-positive viridans streptococci (0.128 microg/ml versus 1 microg/ml). The in vitro activity of telithromycin was high, irrespective of the erythromycin susceptibility and the mechanism of erythromycin resistance identified.

Anti-Bacterial Agents↗

Single-dose rifampin prophylaxis for experimental endocarditis induced by high bacterial inocula of viridans streptococci.

In rats challenged with viridans streptococci poorly susceptible to antibiotic killing, single doses of antibiotics only prevent endocarditis induced by bacterial inoculum sizes that produce disease in 90% of control animals (ID90): additional doses are required to protect against inocula exceeding the ID90. We investigated whether single-dose rifampin would extend the efficacy of single-dose prophylaxis to inocula exceeding the ID90. We used two strains of viridans streptococci highly susceptible to killing by rifampin and two resistant strains. All rats were injected with 10-1,000 times the ID90 of the four strains. Single-dose rifampin successfully prevented endocarditis due to all four strains. A few prophylaxis failures were observed after challenge with the two poorly susceptible strains, but in vivo emergence of resistant variants did not account for these failures. Thus, rifampin was the first antibiotic given as a single dose that successfully prevented experimental streptococcus endocarditis after challenge with high bacterial inocula.

Adhesiveness↗

Antibiotic sensitivities of Streptococcus pneumoniae, viridans streptococci, and group A hemolytic streptococci isolated from the maxillary and ethmoid sinuses.

OBJECTIVES: To investigate antibiotic sensitivities of Streptococcus pneumoniae, viridans streptococci, and group A hemolytic streptococci isolated from the culture materials obtained from the sinuses of patients undergoing functional endoscopic sinus surgery due to chronic sinusitis. PATIENTS AND METHODS: We recruited 93 patients (63 males, 30 females; mean age 36+/-17.5; range 19 to 68 years) who underwent functional endoscopic sinus surgery due to chronic sinusitis. Before surgical intervention, in order to eliminate a possible contamination from the skin and neighboring structures, nasal mucosa was cleansed with povidone-iodine solution. Nasal smear samples were obtained from all the patients before and after applying povidone-iodine solution. Streptococcus pneumoniae, viridans streptococci and group A hemolytic streptococci that were isolated from the cultures were tested for antibiotic sensitivity. RESULTS: The number of anaerobic bacteria isolated from 58 patients (62.3%) before applying povidone-iodine was 72, following the application of povidone-iodine a total of 16 microorganisms were identified from 12 patients (12.9%). Microorganisms were isolated from 95.6% (89/93) of the samples obtained from the maxillary sinuses and 91.3% (85/93) of the samples obtained from the ethmoid sinuses. The most commonly identified microorganisms from both sinuses were coagulase negative staphylococcus followed by viridans streptococci, coagulase positive staphylococcus, Streptococcus pneumoniae and group A hemolytic streptococci. For viridans streptococcal strains that were isolated, 33.3% were resistant to tetracycline, 23.8% to chloramphenicol, and 19.04% to penicillin. Hemolytic streptococci strains were sensitive to penicillin, ofloxacin, ceftriaxone, and cefepime in all the groups; however, they had 50% resistance to erythromycin and chloramphenicol and 100% resistance to tetracycline. The resistance pattern of the isolated Streptococcus pneumoniae strains were as follows: 25% to penicillin, 66.6% to trimethoprim/sulfamethoxazole, 41.6% to erythromycin, 58.3% to tetracycline, 33.3% to chloramphenicol and 16.6% to rifampin. All of the isolated strains were sensitive to vancomycin. CONCLUSION: We suggest that identification of strains that are resistant to penicillin and other antibiotics is an important tool for choosing empirical treatment for Streptococcus pneumoniae, viridans streptococci, and group A hemolytic streptococci in clinical practice. Viridans streptococci which are frequently isolated from chronic sinusitis patients should be kept in mind.

Adult↗

Growth of Viridans streptococci on human serum alpha1-acid glycoprotein.

Viridans streptococci have emerged as major opportunistic pathogens. We suggest that for these bacteria to proliferate in vivo and cause disease, they must utilize host tissue components. We have therefore examined the ability of all recognized species of viridans streptococci to liberate and utilize the constituent sugars of the glycans of the extensively sialylated human serum alpha1-acid glycoprotein (AGP) as the sole source of carbohydrate to support in vitro growth. Analysis of residual glycans following bacterial growth was performed by high-pH anion exchange chromatography with pulsed amperometric detection and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Only those species which produced sialidase-namely, Streptococcus oralis, S. intermedius, and S. defectivus--grew on AGP. The extent of degradation of glycans was dependent on the particular glycosidases produced by the bacteria. S. defectivus produced only a sialidase which released the terminal N-acetylneuraminic acid residues of the glycans, and the liberated sugar was utilized. S. intermedius also produced beta-galactosidase and beta-N-acetylglucosaminidase, which removed galactose and N-acetylglucosamine from desialylated glycans, all of which again were utilized by the organism. S. oralis produced beta-galactosidase, beta-N-acetylglucosaminidase, and alpha-fucosidase and novel alpha- and beta-mannosidases which were apparent only from the analysis of the residual sugars of AGP. S. oralis cleaved all the sugars from AGP except for 22% of the N-acetylglucosamine. The residual N-acetylglucosamine residues remaining were those linked to the asparagine of the peptide backbone. All the monosaccharides released by S. oralis from AGP, with the exception of fucose, were utilized. Sialidase production may be a key factor for growth of these species of viridans streptococci on glycoproteins in vivo, since they are commonly associated with extra-oral diseases, with S. oralis emerging as an important pathogen.

Acetylglucosaminidase↗

Adults with meningitis caused by viridans streptococci.

BACKGROUND: We analyzed the clinical features and therapeutic outcomes of adults with meningitis caused by viridans streptococci. PATIENTS AND METHODS: 12 adult patients with meningitis caused by viridans streptococci were enrolled in this study. Clinical data were collected over a period of 15 years. RESULTS: Of the 12 patients, 11 patients had community-acquired meningitis, while one had nosocomially acquired meningitis. 11 contracted the spontaneous form and one contracted the postneurosurgical form. All isolates were susceptible to penicillin. The portals of entry of infection were determined in all 12 patients; five patients had otopharyngeal infections with or without their being spread hematogenously. The infections in six patients were spread hematogenously, but one of them was spread hematogenously with endocarditis. One patient became infected after a craniotomy. The patients infected by viridans streptococci had a high incidence of focal suppuration and cerebral vasculitis but no deaths occurred. CONCLUSION: Adult bacterial meningitis caused by viridans streptococci is not uncommon and otopharyngeal infection appears to be an important portal of entry. Clinical manifestations varied according to the different underlying conditions. The results of this study also demonstrate the high incidence of intracranial focal suppuration and cerebral vasculitis concomitant with meningitis. Penicillin remains the treatment of choice for patients with meningitis caused by viridans streptococci. Therapeutic outcome is favorable for patients who receive prompt treatment.

Adult↗