Serious infections due to group G streptoccocci: Report of 15 cases with in vitro-in vivo correlations

Serious infections due to group G streptococci have been infrequently reported. Fifteen such cases are described. Endovascular infection, particularly endocarditis, and septic arthritis were the most common clinical syndromes observed. Despite exquisite in vitro sensitivity of group G streptococci to penicillin G, the in vivo clinical response was disappointing in six of nine patients with either endocarditis or septic arthritis. The group G streptococcal isolates from the patients in this study were uniformly sensitive to the inhibitory and killing action of penicillin G, ampicillin, cefotaxime, cephalothin, cefoxitin, and vancomycin. In contrast, clindamycin, erythromycin, and chloramphenicol had relatively poor bactericidal activity against these strains, including several “tolerant” strains. Timed-kill studies with penicillin G revealed impaired killing of group G streptococci at in vitro conditions of high inocula and stationary growth phases. This may partially explain the poor clinical responses in cases of group G streptococcal endocarditis.     

Group B streptococcal endocarditis: report of seven cases and review of the literature, 1962-1985

Infective endocarditis is an uncommon manifestation of group B streptococcal disease. Seven cases of group B streptococcal endocarditis are reported herein. Another fifty-five cases published in the literature since 1962 are reviewed: the male to female ratio was 1.4:1. The average age was 53.8 years, and 45% of patients were 60 years of age or older. Two cases of nonsocomial endocarditis and two cases of polymicrobial endocarditis were identified. There were five cases of prosthetic valve endocarditis. Mitral and aortic valvular involvement were present in 48% and 29% of cases, respectively. Underlying heart disease was found in more than half of the cases. Rheumatic heart disease was the commonest underlying cardiac condition. Noncardiac underlying conditions included diabetes mellitus, alcoholism, pregnancy, intravenous drug abuse, and genitourinary disease. Onset was varied as was initial presentation of the disease. Large arterial thrombi were common. Overall mortality was 43.5%. Penicillin is the treatment of choice for group B streptococcal endocarditis. However, based on in vitro and in vivo studies as well as case reports, some authors feel that the combination of penicillin and an aminoglycoside is a superior regimen. Cephalothin or vancomycin are alternatives for patients who are allergic to penicillin.     

Group B streptococcal endocarditis of tricuspid valve

We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only.     

Effect of penicillin resistance on presentation and outcome of nonenterococcal streptococcal infective endocarditis

BACKGROUND AND AIMS: Most cases of infective endocarditis are caused by nonenterococcal streptococci. The emergence of strains resistant to penicillin is increasingly recognized worldwide. This study sought to assess the effect of penicillin resistance on presentation and outcome of streptococcal endocarditis. METHODS: A retrospective study was conducted in a single tertiary care hospital. RESULTS: Between August 1996 and December 2004, patients infected with nonenterococcal streptococcal endocarditis and known minimal inhibitory concentrations (MICs) to penicillin were included in this study. A total of 62 cases were identified: 48 (77%) cases of the streptococcal endocarditis were caused by viridans streptococci. The most common species groups identified were Streptococcus mitis in 12 (19%) cases, Streptococcus oralis in 9 (15%) cases, Streptococcus sanguis in 7 (11%) cases and Streptococcus mutans in 7 (11%) cases. There were 36 male and 26 female patients with a median age of 46 years (range: 1-85). Twenty-two patients (35%) had peripheral embolization and 10 patients (16%) died in hospital. Twenty-eight (45%) of the 62 patients were infected with streptococcal strains of MICs > or =0.125 microg/ml to penicillin. Infection with streptococcal strains of MICs > or =0.125 microg/ml to penicillin was associated with a lower incidence of all-site embolization, but was not associated with higher mortality or increased frequency of surgery. CONCLUSIONS: High-level penicillin resistance of the streptococci responsible for endocarditis was increasingly common and medical therapy with vancomycin had a good response. Penicillin resistance was associated with a decreased risk of embolization, but was not associated with higher mortality.     

Treatment of endocarditis caused by relatively resistant nonenterococcal streptococci: is penicillin enough?

Most cases of endocarditis are caused by nonenterococcal streptococci. Some of these organisms are classified as relatively resistant to penicillin on the basis of minimum inhibitory concentrations (MICs) greater than 0.1-0.2 microgram/mL. Almost all authorities recommend that endocarditis caused by relatively resistant streptococci be treated with high doses of penicillin combined with 2-6 weeks of an aminoglycoside rather than the potentially shorter, less toxic, and more flexible regimens used for exquisitely sensitive streptococci (MIC, less than 0.1-0.2 microgram of penicillin/mL). The data to support this recommendation are limited and inconclusive. We review the relevant clinical experience, experimental models, and theoretical considerations. Penicillin alone is probably adequate therapy for most cases of native valve endocarditis caused by relatively resistant streptococci; in certain patients, it may be the preferred treatment.     

Penicillin therapy for treatment of experimental endocarditis caused by viridans streptococci in animals

We studied the efficacy of penicillin and penicillin combined with streptomycin in the treatment of experimental endocarditis caused by viridans streptococci that are susceptible, tolerant, or relatively resistant to penicillin. Rabbits with experimental endocarditis were treated with procaine penicillin (1.5 X 10(5) U/kg) administered twice daily or with procaine penicillin (1.5 X 10(5) U/kg) plus streptomycin (20 mg/kg) administered twice daily for five days. Compared with control animals, animals treated with penicillin alone experienced a significant reduction (P less than .001) of colony forming units per gram of cardiac valve vegetations when infected with streptococci that are susceptible, tolerant, or resistant to penicillin. This antibiotic alone was less effective against streptococci that were tolerant or resistant to penicillin than against streptococci susceptible to the drug (P less than .01). The combination of penicillin and streptomycin was more effective therapy than was penicillin alone in animals with penicillin-tolerant or penicillin-resistant streptococci causing endocarditis (P less than .01). Penicillin-streptomycin therapy was less active against penicillin-resistant strains than against either penicillin-tolerant (P less than .04) or penicillin-susceptible (P less than .01) strains. The results of our study suggest that tolerance or relative resistance to penicillin in strains of viridans streptococci influences the response to therapy with penicillin alone or penicillin combined with streptomycin in the treatment of experimental endocarditis caused by viridans streptococci.     

Streptococcus bovis endocarditis

Three cases of endocarditis caused by a nonenterococcal group D streptococcus, Streptococcus bovis, are reported. The clinical picture in these cases was similar to that of subacute endocarditis caused by Streptococcus viridans or enterococcus. All patients were treated with a combination of penicillin and gentamicin for 4 to 6 weeks. Two patients were cured and one died of pulmonary edema without evidence of active infection at necropsy. The in vitro data suggest that Strep. bovis is more susceptible to penicillin than enterococcus and that penicillin or vancomycin in combination with one of the aminoglycoside antibiotics acts synergistically with it against Strep. bovis. Growth in a medium containing 6.5 per cent sodium chloride should be used by the clinical microbiology laboratory to differentiate the nonenterococcal group D streptococcus from the enterococcus.     

Optimal therapy for enterococcal endocarditis

Enterococcal endocarditis accounts for an increasing proportion of cases of endocarditis in recent years. The combination of a penicillin and an aminoglycoside has become an accepted standard of treatment for this disease. However, the optimal choice of antibiotics, duration of therapy, and timing of surgical intervention remain controversial. This study reviews the presentation, clinical course, treatment, and outcome in 37 patients with 42 separate episodes of enterococcal endocarditis at four Yale University hospitals. Patients treated with aminoglycosides and penicillins or vancomycin had significantly better outcomes than those who did not receive aminoglycosides. However, the duration of aminoglycoside therapy (more than four versus less than four weeks) did not appear to affect outcome significantly. These results suggest that excellent cure rates may be achieved after treatment for less than four weeks with an aminoglycoside in combination with penicillin or vancomycin, thus potentially avoiding significant renal and vestibular toxicity.     

Streptococcal meningitis in adult patients: current epidemiology and clinical spectrum.

Streptococci other than Streptococcus pneumoniae are a rare cause of bacterial meningitis in adults. We report 29 cases of streptococcal meningitis (1977-1997). The patients comprised 19 men and 10 women, with a mean age +/- standard deviation of 47 +/- 18 years. Nine cases were secondary to neurosurgical procedures, seven to brain abscess, five to cerebrospinal fluid pericranial fistula, and three to endocarditis. Causative microorganisms included the following: viridans group streptococci, 20 cases; anaerobic streptococci, 3; Streptococcus agalactiae, 3; Streptococcus bovis, 2; and Streptococcus pyogenes, 1. Four Streptococcus mitis strains showed decreased susceptibility to penicillin (MIC, 0.5-2 microg/mL). Five patients (17%) died. The infection is increasing in the hospital setting. Streptococci resistant to penicillin should be considered in the empirical treatment of nosocomial meningitis. In cases of community-acquired infection, anaerobic streptococci or streptococci of the Streptococcus milleri group should alert the clinician to the presence of an undiagnosed brain abscess, whereas oral streptococci of the viridans group suggest the diagnosis of bacterial endocarditis.     

Endocarditis due to group D streptococci. Comparison of disease caused by streptococcus bovis with that produced by the enterococci

The group D streptococci include the nonenterococcal Streptococcus bovis in addition to the classic enterococci. Endocarditis due to Strep. bovis has received little previous attention in the medical literature. A review of all cases of group D streptococcal endocarditis seen at the Massachusetts General Hospital between 1964 and 1973 revealed 14 cases caused by Strep. bovis and 15 by enterococci. There were only minor differences in the clinical presentations of endocarditis caused by these two groups of organisms. Although it contains the group D antigen Strep. bovis behaved like Strep. viridans in producing endocarditis. Moreover, the strains of Strep. bovis in this study were much more susceptible to penicillin than the enterococci. Therapy of severe enterococcal infections requires penicillin plus an aminoglycoside antibiotic whereas the present study strongly suggests that penicillin alone is adequate therapy for endocarditis due to Strep. bovis.     

Vancomycin therapy of bacterial endocarditis.

Fifteen patients with bacterial endocarditis were treated with vancomycin between 1967 and 1976. The indications for vancomycin therapy were penicillin-cephalosporin allergy in six patients, antibiotic resistant bacteria in six, initial therapy in one and culture-negative endocarditis in two. The causative microorganisms were Staph. epidermidis (four patients), Staph. aureus (two patients), diphtheroids (four patients), viridans streptococci (two patients) and enterococci (one patient). Minimum inhibitory concentrations of vancomycin for these organisms ranged from 0.8 to 3.1 micrograms/ml. The patients received vancomycin for two to 10 weeks (mean five weeks). Cure was achieved in 13 patients, including six with prosthetic valve endocarditis (PVE). Two patients had a relapse of PVE and cultures of blood or heart valve were positive within two months of vancomycin therapy. Vancomycin serum levels did not exceed 50 micrograms/ml, and no serious drug toxicity was encountered in any patient. Three patients had minimal audiogram changes beyond the social hearing range. One patient had mild phlebitis and a rash, and one patient had a transient leukopenia. Vancomycin is an effective nontoxic antibiotic in patients with endocarditis when penicillin or cephalosporin therapy is not appropriate.     

Group G streptococcal endocarditis: two case reports, a review of the literature and recommendations for treatment

Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis.     

Pneumococcal endocarditis: report of a series and review of the literature

Pneumococcal endocarditis has declined sharply in incidence since the advent of penicillin but remains a potentially lethal infection. From 1980 to 1984, pneumococcal endocarditis was diagnosed in seven patients--four adults and three infants. Apart from one patient who had had a splenectomy, there were no recognizable predisposing factors to infection due to Streptococcus pneumoniae, although all three children were younger than 15 months of age. Congenital heart disease was present in two patients, calcific aortic disease in one, and mitral valve prolapse in a fourth. The remaining three patients had previously normal hearts. Meningitis occurred in five (71%) of the seven patients. Five patients were cured of their infection: four by medical therapy alone (penicillin or vancomycin), and a fifth, by medical therapy plus valvular debridement. Two patients died: one with intractable heart failure, and the second, from the complications of cardiac surgery. Penicillin alone is effective therapy for pneumococcal endocarditis. Patients unable to tolerate penicillin may be treated with vancomycin.     

Special issues in the management of infective endocarditis caused by gram-positive cocci

Gram-positive cocci, mainly streptococci and staphylococci, continue to cause the majority of cases of infective endocarditis. Among the streptococci causing IE, the long-standing predominance of oral or viridans-group streptococci has progressively faded, while the number of cases caused by "enteric streptococci" (Streptococcus bovis and enterococci) has increased. While most oral streptococci and S. bovis strains remain fully sensitive to penicillin, nutritionally variant streptococci--now renamed Abiotrophia--and enterococci can exhibit resistance to penicillin and/or glycopeptides that makes endocarditis more difficult to treat. Among the staphylococci causing endocarditis, the increasing proportion of coagulase-negative and methicillin-resistant strains observed in recent years has changed the approach to choice of antibiotic therapy. The purpose of this paper is to focus on some new aspects of the management of antibiotic therapy of IE due to streptococci and staphylococci, including recent developments such as once-daily aminoglycoside administration in IE, outpatient antibiotic therapy, and the evaluation of new antibiotics.     

Serious infections in adults due to group B streptococci: Clinical and serotypic characterization

Serious infections in adults due to group B streptococci have been infrequently reported. We describe 24 such patients. Bacteremic pyelonephritis, pneumonitis and endometritis were the most common clinical syndromes observed. Group B streptococcal infections tended to occur in patients with underlying illnesses, particularly genitourinary disorders and diabetes mellitus. Mortality was surprisingly low (8 per cent). Type III was the serotype most commonly isolated, and there was no significant correlation of different serotypes with specific organ-system involvement. Group B streptococcal isolates from these patients were uniformly sensitive to penicillin, ampicillin, cephalothin, chloramphenicol, erythromycin and clindamycin; all were highly resistant to kanamycin. Eighty-seven per cent were resistant to tetracycline. Although consistently sensitive to penicillin, the minimal inhibitory concentrations were significantly higher for group B than group A streptococci (p < 0.0005).     

Group C streptococcal endocarditis presenting as clinical meningitis: Report of a case and review of the literature

Lancefield group C streptococci are known to be pathogenic in a number of animal species, but cause human disease much less commonly than do streptococci of scrogroups A or B. Reported cases of bacteremic infection, pneumonia or meningitis in humans have been very severe with a grave prognosis. The authors describe a patient who presented with classic clinical and laboratory evidence of bacterial meningitis which proved to be a complication of endocarditis caused by a group C streptococcus. This is the first reported case in which meningitis was the presenting manifestation of group C streptococcal endocarditis and is only the second case in which group C streptococcal meningitis and endocarditis have been associated in the same patient. A total of 13 cases of group C streptococcal meningitis have now been reported in the medical literature. Five of these patients died, and four others recovered only to be left with neurological sequelae. The current case confirms the seriousness of group C streptococcal infections in humans. Such infections are associated with a poor prognosis despite apparently adequate antimicrobial therapy.     

Endocarditis caused by penicillin-resistant viridans streptococci: 2 cases and controversies in therapy.

Although penicillin-resistant viridans streptococci have been isolated from samples from the mouth, blood, and wounds in increasing numbers, viridans streptococci isolated from patients with endocarditis have remained sensitive to penicillin for the past 5 decades. We report the cases of 2 patients with penicillin-resistant viridans streptococcal endocarditis, review 6 other cases from the literature, and summarize 2 studies that used an animal model of penicillin-resistant viridans streptococcal endocarditis.     

Invasive streptococcal infections in the era before the acquired immune deficiency syndrome: a 10 years' compilation of patients with streptococcal bacteraemia in North Yorkshire

Significant streptococcal (non-pneumococcal, non-enterococcal) bacteraemia was detected in 100 patients in two Health Districts of North Yorkshire in the decade 1978-1988. Patients with these infections accounted for 11% of the total 902 patients in the districts in whom bacteraemia was diagnosed during the period. Infection was most often seen with beta-haemolytic streptococci (52 patients) comprising Lancefield group A (Streptococcus pyogenes) (20 patients), group B (13), group C (5), group G (9), haemolytic Streptococcus milleri and non-groupable streptococci (5). The wide variety of serious infections included cellulitis, abscess, septicaemia, pneumonia, septic arthritis, necrotising fasciitis, acute endocarditis and mycotic aneurysm. Of these 52 patients, 21 (40%) died. alpha-Haemolytic streptococcal bacteraemia was diagnosed in 38 patients of whom 24 (63%) suffered from endocarditis and three (8%) died. Three of ten patients with non-haemolytic or anaerobic streptococcal bacteraemia died also. Six of the 100 patients with streptococcal bacteraemia had concomitant acute virus infections. Of the total 56 patients with infective endocarditis diagnosed in the districts during the period, streptococci were responsible in 30 (54%) of them. The predisposing factors, clinical features and outcome of the infections are described and discussed.     

Endocardite tricuspide du post-partum à streptocoque B

The B streptococcal endocarditis are very rare. They primarily affect the left heart valves, the achievement of the tricuspid valve is exceptional. We report a young patient aged of 36 years who presented in postpartum a tricuspid endocarditis with streptococcus B. She was treated by third-generation cephalosporin and aminoglycoside. The evolution after 5 days of antibiotic therapy was marked by a rapid valvular destruction with worsening tricuspid insufficiency leading to death of the patient. This is the 23rd case of tricuspid endocarditis streptococcal B reported in the literature. The mortality of this disease reached 36% in the absence of surgical treatment. The medico-surgical approach is the treatment of choice for these patients.     

Synergy of vancomycin plus cefazolin or cephalothin against methicillin-resistance Staphylococcus epidermidis.

The in vitro activity of cephalothin, cefazolin, and vancomycin against 25 isolates of methicillin-resistant Staphylococcus epidermidis was determined by means of a broth dilution technique with two sizes of inoculum. The size of the inoculum had a marked effect on the minimal inhibitory concentrations and the minimal bactericidal concentrations of all three antibiotics. With a small inoculum, 100% of the isolates were inhibited by 3.12 micrograms of vancomycin/ml, 76% by 12.5 micrograms of cephalothin/ml, and 64% by 12.5 micrograms of cefazolin/ml. With a large inoculum 100% of the isolates were inhibited by 200 micrograms of vancomycin/ml, 40% by 12.5 micrograms of cephalothin/ml, and 12% by 12.5 micrograms of cefazolin/ml. As determined by a tube dilution checkerboard technique for both sizes of inoculum, the combination of vancomycin plus cephalothin was synergistic against methicillin-resistant S. epidermidis in 45 of 50 cases, and the combination of vancomycin plus cefazolin was synergistic in 39 or 50 cases. These data from in vitro studies suggest that these antibiotic combinations should be evaluated clinically in patients with severe infections caused by methicillin-resistant S. epidermidis.