A Pharmacoepidemiologic Study of the Safety and Effectiveness of Clindamycin in Infants

Background Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse events, as well as antibiotic effectiveness in infants. Methods This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997-2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia. Results A total of 4089 infants received clindamycin at a median (25th-75th percentile) dose of 15 mg/kg/d (12-16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 [1.04-3.63]), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course. Conclusions Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.