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In an observational study on streptococcal endocarditis, a successful outcome was nearly three times more likely with a 4-hourly dosing interval than with a 6-hourly one.

Although penicillin remains the cornerstone of antibiotic treatment for streptococcal infective endocarditis, guidelines have differed with respect to the suggested dosing interval. Whether such differences affect outcome is unclear. Now, researchers at the University of Leeds, England, have published data from a retrospective series of 212 patients with streptococcal endocarditis treated at their institution between 2000 and 2011 that shed some light on this clinical problem.

Sixty percent of the 150 patients treated with a 4-hourly penicillin regimen were cured compared with 37% of the 62 patients treated with a 6-hourly regimen. A 4-hourly dosing interval was the only treatment-related parameter significantly associated with successful initial therapy (odds ratio, 2.79; 95% confidence interval, 1.43–5.62). Evidence of abscess or severe valvular regurgitation on initial echocardiography decreased the likelihood of successful initial penicillin therapy (OR, 0.30; 95% CI, 0.13–0.66). In a stepwise multivariate regression analysis, patient age, sex, Charlson score, renal impairment, valve type affected, valve location, total daily penicillin dose, penicillin MIC of the isolate, and concurrent prescription of gentamicin had no effect on outcome.

Comment

Penicillin is a safe antibiotic with a narrow spectrum and good activity against the streptococci that cause endocarditis. The study findings are not really surprising, given penicillin's short half-life and the shorter periods above the minimum inhibitory concentration with less-frequent dosing. Interestingly, this study did not suggest a positive effect of gentamicin on endocarditis outcomes — another area of controversy.

CITATION:

Sandoe JAT et al. What is the effect of penicillin dosing interval on outcomes in streptococcal infective endocarditis? J Antimicrob Chemother 2013 Jun 13; [PubMed® abstract]