Project Details

Duration of Post-Discontinuation Antibiotic Exposures in Premature Infants and Associated Outcomes

Angelique Boutzoukas, MD

Summary

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.

Publications:

Boutzoukas AE, Balevic SJ, Hemmersbach-Miller M, Winokur PL, Gu K, Chan AW, Cohen-Wolkowiez M, Conrad T, An G, Kirkpatrick CMJ, Swamy GK, Walter EB, Schmader KE, Landersdorfer CB. Population Pharmacokinetics of Meropenem Across the Adult Lifespan. Clin Pharmacokinet. 2025 Feb;64(2):229-241. doi: 10.1007/s40262-024-01465-1. Epub 2024 Dec 16. PMID: 39681779; PMCID: PMC12181987.

Boutzoukas AE, Dai W, Cober E, Abbo LM, Komarow L, Chen L, Hill C, Satlin MJ, Grant M, Fries BC, Patel G, McCarty TP, Arias CA, Bonomo RA, van Duin D for the Antibacterial Resistance Leadership Group and the MDRO Network Investigators. Carbapenem-resistant Enterobacterales in solid organ transplant recipients. American Journal of Transplantation. 9 November 2024. 10.1016/j.ajt.2024.10.020. PMID 39522694

Boutzoukas A*, Mackow N*, Giri A, Komarow L, Hill C, Chen L, Doi Y, Satlin MJ, Arias C, Wang M, Mora Moreo L, Herc E, Cober E, Weston G, Patel R, Bonomo R, Fowler V, van Duin D. Increased Mortality in Hospital- compared to Community-Onset Carbapenem-resistant Enterobacterales Infections. Journal of Antimicrobial Chemotherapy. Sept 2024. 10.1093/jac/dkae306 (* indicates co-fist authorship). PMID: 39236214

Boutzoukas AE, Komarow L, Chen L, Hanson B, Kanj SS, Liu Z, Mendoza SS, Ordoñez K, Wang M, Paterson DL, Evans S, Ge L, Giri A, Hill C, Baum K, Bonomo RA, Kreiswirth B, Patel R, Arias CA, Chambers HF, Fowler VG, van Duin D. International epidemiology of carbapenemase-producing Escherichia coli. Clinical Infectious Diseases. Aug 2023.10.1093/cid/ciad288. PMID 37154071

Jiang J, Komarow L, Hill C, Boutzoukas AE, Hanson B, Arias CA, Bonomo RA, Evans S, Doi Y, Satlin MJ, Weston G, Cober E, Valderrama-Beltran SL, Mendoza SS, Liu Z, Fries BC, Tambyah PA, Chambers HF, Fowler Jr VG, van Duin D, Kreiswirth BN, Chen L. Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort. The Journal of Infectious Diseases. 12 December 2024. 10.1093/infdis/jiae616