Duration of protective effect after benzathine penicillin G prophylaxis for recurrent cellulitis: a 14-day window of efficacy

Abstract Purpose Following the administration of prophylactic intramuscular benzathine penicillin G (BPG) for recurrent cellulitis, the precise duration of its protective effect remains unclear. We aimed to evaluate the prophylactic efficacy of BPG against recurrent cellulitis under various assumed durations of prophylaxis. Methods This retrospective observational study included 73 patients who received BPG prophylaxis for cellulitis. We compared cellulitis episodes between the prophylaxis and non-prophylaxis periods, and analyzed the timing of recurrence after BPG administration. A multivariable time-varying Cox regression analysis was performed, with time after BPG injection as the time-varying covariate. Results An analysis of 592 patient-years revealed 310 recurrences. Under the assumption of a 14-day prophylactic window after BPG administration, the recurrence rate was significantly lower during the prophylaxis period than during the non-prophylaxis period (incidence rate ratio [IRR], 0.57; 95% confidence interval [CI], 0.33–0.99; P = .045). In contrast, when assuming prophylactic windows of 21 and 28 days, the IRRs were 0.74 ( P = .154) and 0.92 ( P = .642), respectively. Among the cellulitis episodes that occurred within 10 weeks of BPG administration, 43% occurred between days 15 and 28. After adjusting for lymphedema, the risk of recurrence was significantly lower within 14 days of BPG administration (adjusted hazard ratio, 0.54; 95% CI, 0.31–0.94; P = .030). Conclusion The protective effect of intramuscular BPG against recurrent cellulitis was most pronounced during the first two weeks after administration, supporting the potential utility of individualized, shorter dosing intervals.