Duration of Post-Discontinuation Antibiotic Exposures in Premature Infants and Associated Outcomes
BACKGROUND: Preliminary data suggests that premature infants receiving certain antibiotics (ampicillin, cefepime, and piperacillin/tazobactam) have therapeutic concentrations of antibiotics for long after these drugs are discontinued. The presence of prolonged exposures after drug discontinuation in premature infants has yet to be confirmed in a clinical setting, nor is it known whether prolonged post-antibiotic exposures have implications in acquisition of antibiotic resistance. GAP: This study will examine whether premature infants face prolonged antibiotic exposures following antibiotic discontinuation and examine the impact of prolonged antibiotic exposures on future antibiotic-resistant infections. HYPOTHESIS: Our primary hypothesis is that premature infants receiving ampicillin, cefepime, or piperacillin-tazobactam at current dosing recommendations will have prolonged therapeutic exposures for (>48 hours for ampicillin, >24 hours for cefepime and piperacillin-tazobactam) following discontinuation of antibiotics. Our secondary hypothesis is that prolonged post-discontinuation antibiotic exposures are associated with increased likelihood of future infections with resistance to previously prescribed antibiotics. METHODS: First, I will conduct a prospective, single center study using opportunistic samples from premature infants in the Duke NICU during administration and after discontinuation of antibiotics of interest (AIM 1); second, I will leverage the Pediatrix data warehouse to apply models of post-discontinuation antibiotic exposure durations and determine whether prolonged exposures are associated with future antibiotic-resistance in premature infants (AIM 2). RESULTS: Pending. IMPACT: This proposal will answer critical questions in a highly relevant population, premature infants, regarding durations of antimicrobial therapeutic exposures and potential effects of these exposures on antimicrobial resistance. Increasing foundational knowledge relating to prolonged and unwanted antibiotic exposures and their relationships with antibiotic resistance is essential to improving antibiotic stewardship efforts and related outcomes for premature infants.