Antibiotic treatment of streptococcal and enterococcal endocarditis: an overview

The management of streptococcal and enterococcal endocarditis has changed in recent years with the development of effective new regimens that are easier to administer, but resistance to commonly used antibiotics has appeared, especially among enterococci. Beta-lactam antibiotics either alone or in combination are suitable for most patients with viridans streptococci. Streptococci bovis, and S. pneumoniae, but alternative regimens are necessary for special situations. Group B, C and G streptococci respond best to the combination of a penicillin and an aminoglycoside. Enterococci are relatively resistant to penicillins and cephalosporins and strains resistant to beta-lactams, glycopeptides and aminoglycosides have become more common lately. Strategies are proposed dependent on the resistance of the organisms, but it is recognized that medical failure is not uncommon and surgical removal of the infected valve may be the only curative treatmen

Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of penicillin

Penicillin prophylaxis against experimental endocarditis due to a strain of Streptococcus intermedtus isolated from a patient with endocarditis was studied in rats. The minimum bactericidal concentration of penicillin for this strain was more than 64 mg/l and was higher than the peak penicillin serum level obtained in rats 30 min after the iv injection of 60 mg/kg, and in man after an oral dose of 2 g of phenoxymethyl penicillin. Moreover timed kill curves performed in the presence of 64 mg/l of penicillin showed no decrease in the number of colony-forming units during the first 6 h of incubation and only a 95% decrease after 24 h. In addition, no bactericidal activity could be detected in the serum 30 min after penicillin injection, that is at the time of bacterial challenge. Using the minimum bacterial inoculum needed to produce endocarditis in 90% of control animals (ID90), penicillin successfully prevented endocarditis due to this strain. We conclude that penicillin may prevent streptococcal endocarditis by other mechanisms than bacterial killin

Relevance of animal models to the prophylaxis of infective endocarditis

Intravascular or cardiac endothelial lesions may become colonized during bacteraemic episodes and lead to the development of bacterial endocarditis (BE). It has therefore long been recommended that patients with known cardiac lesions receive prophylactic antibiotics before undergoing procedures that might release bacteria into the blood stream. Because clinical trials of antibiotic prophylaxis of endocarditis cannot be conducted in humans for ethical as well as for statistical reasons (Durack, 1985), the questions of which antibiotic, what dosage, and for how long are a matter of controversy. Unfortunately, these questions can only be studied in animals, with all the limitations that this type of approach brings with it. However, animal experimental studies have helped in understanding the conditions and, to some extent, the mode of action of antibiotics in preventing the development of endocardial infection, thus allowing some rationale for devising prophylactic recommendations for the various patients at risk of developing B

Endocarditis Prophylaxis: From Experimental Models to Human Recommendation

Animal models of endocarditis have helped understanding of the mode of action of antibiotics in prophylaxis. During bacteraemia, some microorganisms will adhere to damaged cardiac valves. The proportion of bacteria that will adhere depends largely on intrinsic properties of the strain. In the absence of antibiotics, the microorganisms will either be eliminated by local host defence mechanisms if the inoculum is low enough or will begin to grow approximately 2 h after the development of bacteraemia and endocarditis. In the presence of antibiotics, the growth of adherent bacteria is inhibited and local host defences have longer to eliminate the bacteria. In cases where the number of adherent bacteria is relatively low, a short period in inhibitory antibiotic activity (6 hours) is sufficient to eliminate the bacteria and lead to successful prophylaxis. If the number of bacteria is high, a longer duration of the inhibitory effect is necessary. These experimental data provide a rationale for practical recommendations for the prophylaxis of endocarditis in human

Successful Prophylaxis Against Experimental Streptococcal Endocarditis with Bacteriostatic Antibiotics

Because bacteriostatic concentrations of vancomycin are effective in prophylaxis against endocarditis due to Streptococcus sanguis in rats, the efficacy of three other bacteriostatic antibiotics was investigated against three different streptococcal species that cause subacute endocarditis in humans: Streptococcus intermedius, S. sanguis, and Streptococcus mitior. Rats were challenged by intravenous injection of 2 × 105 colony-forming units of streptococci 24 hr after intracardiac insertion of a transaortic catheter and 30 min after intravenous injection of various doses of clindamycin, erythromycin, and doxycycline. Significant protection was achieved with all three antibiotics, but only clindamycin was fully effective against all three species at doses that simulated serum levels achievable in humans after oral administration. Endocarditis was prevented by antibiotic concentrations in serum far below minimal bactericidal concentrations for these streptococci. Furthermore, serum at the time of bacterial challenge was not bactericidal. Therefore, single doses of nonbactericidal antibiotics prevented endocarditis in rats by mechanisms other than bacterial killin

Bacterial Brain Abscesses: Factors Influencing Mortality and Sequelae

Thirty-nine cases of brain abscess diagnosed since the advent of the computed tomographic (CT) scan were analyzed for factors influencing the outcome. The mortality rate was 13%, and severe sequelae were present in 22% of the survivors. The mean delay between occurrence of the first symptoms and hospitalization was significantly shorter for the 12 patients with poor outcome (death or severe sequelae) than for the 25 who recovered (fully or with moderate sequelae). Moreover, severely impaired mental status and neurological impairment at admission were associated with a poor outcome in terms of both mortality and sequelae. In all cases with fatal outcome or severe sequelae, the diagnosis was made and treatment was initiated within 24 hours of admission. There was no apparent correlation between the outcome and the presence or type of predisposing factors, the radiological, biological, or microbiological findings, or the treatment modalities. Thus, with the advent of the CT scan and the possibility of early diagnosis and treatment, the prognosis of brain abscess appears to be mainly determined by the rapidity of progression of the disease before hospitalization and the patient's mental status on admissio

Comparison of Single Doses of Amoxicillin or of Amoxicillin-Gentamicin for the Prevention of Endocarditis Caused by Streptococcus faecalis and by Viridans Streptococci

Recent recommendations for the prophylaxis of endocarditis in humans have advocated single doses or short courses of antibiotic combinations (β-lactam plus aminoglycoside) for susceptible patients in whom enterococcal bacteremia might develop or for patients at especially high risk of developing endocarditis (e.g., patients with prosthetic cardiac valves). We tested the prophylactic efficacy (in rats with catheter-induced aortic vegetations) of single doses of amoxicillin plus gentamicin against challenge with various streptococcal strains (two strains of Streptococcus faecalis, one of Streptococcus bovis, and three of viridans streptococci); we then compared this efficacy with that of single doses of amoxicillin alone. Successful prophylaxis against all six strains was achieved with single doses of both amoxicillin alone and amoxicillin plus gentamicin. This protection, however, was limited, for both regimens, to the lowest bacterial-inoculum size producing endocarditis in 90% of control rats and was not extended to higher inocula by using the combination of antibiotics. We concluded that a single dose of amoxicillin alone was protective against enterococcal and nonenterococcal endocarditis in the rat, but that its efficacy was limited and could not be improved by the simultaneous administration of gentamici

Blood samples drawn for culture as a surrogate marker for case-mix adjustment of hospital antibiotic use.

Hospital antibiotic consumption is generally adjusted to occupancy. This study hypothesised that the number of blood culture samples could be a surrogate marker for case-mix adjustment. Antibiotic consumption was compared over 16 consecutive trimesters in one medical ward in terms of patient-days or blood culture samples. Compared with patient-days, measurement adjusted to blood culture samples detected three trimesters with an unusually high consumption, and one trimester with consumption falsely classified as high because of a high incidence of infections. Blood culture numbers enabled easy and accurate identification of periods with a drift in antibiotic consumption ina medical ward