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

Publication ,  Journal Article
Le, J; Greenberg, RG; Benjamin, DK; Yoo, Y; Zimmerman, KO; Cohen-Wolkowiez, M; Wade, KC ...
Published in: J Pediatric Infect Dis Soc
May 28, 2021

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.

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Published In

J Pediatric Infect Dis Soc

DOI

EISSN

2048-7207

Publication Date

May 28, 2021

Volume

10

Issue

5

Start / End Page

615 / 621

Location

England

Related Subject Headings

  • Sepsis
  • Retrospective Studies
  • Infant, Very Low Birth Weight
  • Infant, Newborn
  • Infant
  • Humans
  • Escherichia coli
  • Anti-Bacterial Agents
  • 3213 Paediatrics
  • 3207 Medical microbiology
 

Citation

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Le, J., Greenberg, R. G., Benjamin, D. K., Yoo, Y., Zimmerman, K. O., Cohen-Wolkowiez, M., … Administrative Core Committee of the Best Pharmaceuticals for Children Act–Pediatric Trials Network, . (2021). Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis. J Pediatric Infect Dis Soc, 10(5), 615–621. https://doi.org/10.1093/jpids/piaa172
Le, Jennifer, Rachel G. Greenberg, Daniel K. Benjamin, YoungJun Yoo, Kanecia O. Zimmerman, Michael Cohen-Wolkowiez, Kelly C. Wade, and Kelly C. Administrative Core Committee of the Best Pharmaceuticals for Children Act–Pediatric Trials Network. “Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis.J Pediatric Infect Dis Soc 10, no. 5 (May 28, 2021): 615–21. https://doi.org/10.1093/jpids/piaa172.
Le J, Greenberg RG, Benjamin DK, Yoo Y, Zimmerman KO, Cohen-Wolkowiez M, et al. Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis. J Pediatric Infect Dis Soc. 2021 May 28;10(5):615–21.
Le, Jennifer, et al. “Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis.J Pediatric Infect Dis Soc, vol. 10, no. 5, May 2021, pp. 615–21. Pubmed, doi:10.1093/jpids/piaa172.
Le J, Greenberg RG, Benjamin DK, Yoo Y, Zimmerman KO, Cohen-Wolkowiez M, Wade KC, Administrative Core Committee of the Best Pharmaceuticals for Children Act–Pediatric Trials Network. Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis. J Pediatric Infect Dis Soc. 2021 May 28;10(5):615–621.
Journal cover image

Published In

J Pediatric Infect Dis Soc

DOI

EISSN

2048-7207

Publication Date

May 28, 2021

Volume

10

Issue

5

Start / End Page

615 / 621

Location

England

Related Subject Headings

  • Sepsis
  • Retrospective Studies
  • Infant, Very Low Birth Weight
  • Infant, Newborn
  • Infant
  • Humans
  • Escherichia coli
  • Anti-Bacterial Agents
  • 3213 Paediatrics
  • 3207 Medical microbiology