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

Title: Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis
Authors: Le, Jennifer; Greenberg, Rachel G; Benjamin, Daniel K; Yoo, YoungJun; Zimmerman, Kanecia O; Cohen-Wolkowiez, Michael; Wade, Kelly C; Hornik, Christoph; Zimmerman, Kanecia; Kennel, Phyllis; Beci, Rose; Hornik, Chi Dang; Kearns, Gregory L; Laughon, Matthew; Paul, Ian M; Sullivan, Janice; Wade, Kelly; Delmore, Paula; Taylor-Zapata, Perdita; Lee, June; Anand, Ravinder; Sharma, Gaurav; Simone, Gina; Kaneshige, Kim; Taylor, Lawrence; Green, Thomas
Source: Journal of the Pediatric Infectious Diseases Society, vol 10, iss 5
Publisher Information: eScholarship, University of California
Publication Year: 2021
Collection: University of California: eScholarship
Subject Terms: 3213 Paediatrics (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Hematology (rcdc); Infectious Diseases (rcdc); Sepsis (rcdc); Preterm; Low Birth Weight and Health of the Newborn (rcdc); Pediatric (rcdc); Perinatal Period - Conditions Originating in Perinatal Period (rcdc); Emerging Infectious Diseases (rcdc); Infection (hrcs-hc); 3 Good Health and Well Being (sdg); Anti-Bacterial Agents (mesh); Escherichia coli (mesh); Humans (mesh); Infant (mesh); Infant; Newborn (mesh); Very Low Birth Weight (mesh); Retrospective Studies (mesh); Sepsis (mesh); ampicillin; antimicrobial stewardship; early-onset sepsis; gentamicin; Monte Carlo simulation; neonatal sepsis; neonate; pharmacokinetics
Subject Geographic: 615 - 621
Description: 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 ( 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.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: qt6mz6f9vj; https://escholarship.org/uc/item/6mz6f9vj; https://escholarship.org/content/qt6mz6f9vj/qt6mz6f9vj.pdf
DOI: 10.1093/jpids/piaa172
Availability: https://escholarship.org/uc/item/6mz6f9vj; https://escholarship.org/content/qt6mz6f9vj/qt6mz6f9vj.pdf; https://doi.org/10.1093/jpids/piaa172
Rights: public
Accession Number: edsbas.EE18524B
Database: BASE