Serum penicillin levels in Indian children and adolescents with rheumatic heart disease receiving benzathine penicillin G prophylaxis

Background: Acute rheumatic fever and rheumatic heart disease (RHD) are serious complications of untreated Group A Streptococcal infections. Given that India bears the highest global burden of RHD, optimizing secondary prophylaxis is a public health priority. Concerns regarding the adequacy of the current 3-weekly benzathine penicillin G (BPG) regimen and the lack of pharmacokinetic data in Indian children prompted this study. The objective of the study was to quantify serum penicillin levels in Indian children (aged 5–18 years) with RHD receiving 3-weekly BPG prophylaxis. Methods: Children ( n = 23) with confirmed RHD and compliant with BPG prophylaxis for at least 6 months were enrolled. Intramuscular BPG was administered on day 0, and blood samples were collected at baseline, at 48 h, on day 6, and on day 14 postinjection. Serum penicillin concentrations were measured using a validated assay. A one-compartment pharmacokinetic model was used to estimate concentration–time profiles and duration of protective drug levels. Results: The mean age of participants was 12.87 ± 2.1 years; 52.2% were female. Mean serum penicillin concentrations were 5.21 ± 6.41 ng/mL (day 0), 22.16 ± 22.62 ng/mL (day 2), 20.22 ± 18.11 ng/mL (day 6), and 10.15 ± 7.26 ng/mL (day 14). Levels were significantly higher at all postinjection time points compared to baseline ( P < 0.05). However, only 1/3 of patients maintained serum concentrations above the protective threshold (20 ng/mL) on days 2 and 6, and just one patient (6.2%) did so by day 14. No patient maintained therapeutic levels throughout the 21-day interval. Median duration above 20 ng/mL was 144 h (6 days), and above 10 ng/mL was 336 h (14 days). Conclusions: Most Indian children receiving 3-weekly BPG prophylaxis for RHD do not maintain therapeutic serum penicillin concentrations for >1 week postinjection. These findings highlight the limitations of the current prophylaxis strategy and underscore the need to reassess injection intervals.