What is the effect of penicillin dosing interval on outcomes in streptococcal infective endocarditis?

Penicillin is an important treatment option for streptococcal infective endocarditis (IE), but its short half-life requires frequent re-dosing (4- or 6-hourly). There is a variation between the dosing regimens in different guidelines and consequent differences in the dosing interval. The objective of this study was to examine the relationship between the penicillin dosing interval and outcomes in streptococcal IE. A retrospective study of cases of streptococcal IE was undertaken using the Leeds Endocarditis Service database. Cases were included if the first-line therapy had been penicillin and excluded if patients had received less than 72 h of therapy. Details of antimicrobial therapy and outcomes were collated using strict definitions. Various parameters were considered as independent variables in a multivariate logistic regression analysis. Univariate analysis of categorical data was carried out using a χ(2) test, and analysis of continuous data using an unpaired t-test. Two hundred and twelve cases were included in the final analysis. Of the parameters considered, a 4-hourly dosing interval [unadjusted OR = 2.79 (95% CI 1.43-5.62)] and initial echocardiographic evidence of abscess or severe valve regurgitation [unadjusted OR = 0.30 (95% CI 0.13-0.66)] were the only statistically significant factors associated with the success or failure of penicillin therapy. The odds of a successful outcome were almost three times greater with a 4-hourly regimen than with a 6-hourly regimen. Failure of penicillin therapy had no correlation with the MIC of penicillin or the concurrent administration of gentamicin. Penicillin continues to be an effective therapy for IE. This study suggests that a 4-hourly dosing interval may be relevant in predicting the success of initial medical therapy. Further prospective studies are warranted to evaluate relationships in more detail.