Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis.

BACKGROUND: Premature, very low birth weight (VLBW) neonates are at risk for early-onset sepsis and receive ampicillin and gentamicin post-birth. Antimicrobial stewardship supports short-course antibiotics, but how long antibiotic concentrations remain therapeutic post-last dose is unknown. METHODS: Using Monte Carlo simulations (NONMEM 7.3), we analyzed antibiotic exposures in a retrospective cohort of 34 689 neonates (<1500 g, 22-27 weeks of gestation). Therapeutic exposure for ampicillin and gentamicin was evaluated relative to the minimum inhibitory concentration (MIC) for common pathogens (MIC 0.25-8 mcg/mL for group B streptococcus [GBS] and Escherichia coli). Post-discontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to time when concentration decreased below MIC. RESULTS: Neonates had a median (range) gestational age of 26 (22-27) weeks and BW, 790 g (400-1497) . All ampicillin dosing regimens (50-100 mg/kg every 8-12 hours for 2-6 doses) achieved therapeutic exposures > MIC range. After the last dose, the PDAE mean (95% confidence interval [CI]) ranged from 34 to 50 hours (17-79) for E. coli (MIC 8) and 82 to 104 hours (95% CI: 39-122) for GBS (MIC 0.25); longer PDAE occurred with higher dose, shorter interval, and longer course. Short-course ampicillin (2 doses, 50 mg/kg every 12 hours) provided PDAE 34 hours for E. coli and 82 hours for GBS. Single-dose 5 mg/kg gentamicin provided PDAE > MIC 2 for 26 hours. CONCLUSIONS: In VLBW neonates, ampicillin exposure remains therapeutic long after the last dose. Short-course ampicillin provided therapeutic exposures throughout the typical blood culture incubation period.

Duke Scholars

Author Rachel Gottron Greenberg Pediatrics, Neonatology

Author Daniel Kelly Benjamin Jr. Pediatrics, Infectious Diseases

Author Kanecia Obie Zimmerman Pediatrics, Critical Care Medicine

Author Michael Cohen-Wolkowiez Pediatrics, Infectious Diseases

Author Chi Hornik Pediatrics, Critical Care Medicine