Factors Associated with Loss of Penicillin G Concentrations in Serum After Intramuscular Benzathine Penicillin G Injection: A Meta-analysis.

摘要

Benzathine penicillin G (pen G) is prescribed for treatment and prophylaxis against conditions due to group A streptococcus. The World Health Organization recommends secondary prophylaxis at 3- and 4-week intervals depending on the patient's age and health status. Studies were reviewed for the persistence of serum pen G over the course of 4 weeks after intramuscular injection. Published literature from the PubMed database was reviewed. Thirty-four data sets were analyzed for serum pen G concentration over time. The data were analyzed by (1) survival probability estimates of pen G levels above minimum protective over the course of 4 weeks using a Kaplan-Meier model, and (2) analysis of variance of mean pen G levels over time, including as factors date of publication and health and age of subjects. Weighted mean serum levels across studies were below 0.02microg/ml before 3 weeks. Mean serum pen G concentration decay rates were higher, and the percentage of subjects with serum pen G above minimum protective levels were found to decrease significantly faster in studies performed (1) with healthy subjects than in studies with sick subjects, (2) after 1978 than in studies done before, and (3) with adults than in studies with children. Exponential modeling of percentages of subjects above minimum protective shows that approximately 65% of subjects were above minimum protective levels at 3 weeks and approximately 45% at 4 weeks. Recommendations for prophylaxis should be re-evaluated, with further study of serum pen G levels and dose response in specific target populations.