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Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship

OBJECTIVE: Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. STUDY DESIGN: We simulated ampicillin concentrations in newborns (birthweight<1500g; gestational age 22–27 weeks), summarizing three 48-hour regimens: high 100mg/kg Q8hr, medium 100mg/kg...

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Autores principales: Le, Jennifer, Greenberg, Rachel G., Yoo, YoungJun, Clark, Reese H., Benjamin, Daniel K., Zimmerman, Kanecia O., Cohen-Wolkowiez, Michael, Wade, Kelly C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262754/
https://www.ncbi.nlm.nih.gov/pubmed/35210541
http://dx.doi.org/10.1038/s41372-022-01344-2
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author Le, Jennifer
Greenberg, Rachel G.
Yoo, YoungJun
Clark, Reese H.
Benjamin, Daniel K.
Zimmerman, Kanecia O.
Cohen-Wolkowiez, Michael
Wade, Kelly C.
author_facet Le, Jennifer
Greenberg, Rachel G.
Yoo, YoungJun
Clark, Reese H.
Benjamin, Daniel K.
Zimmerman, Kanecia O.
Cohen-Wolkowiez, Michael
Wade, Kelly C.
author_sort Le, Jennifer
collection PubMed
description OBJECTIVE: Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. STUDY DESIGN: We simulated ampicillin concentrations in newborns (birthweight<1500g; gestational age 22–27 weeks), summarizing three 48-hour regimens: high 100mg/kg Q8hr, medium 100mg/kg Q12hr, and standard 50mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (C(max)≤140mcg/mL), and duration limited to 48 hours. RESULTS: Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 hours, but C(max) exceeded the neurotoxicity threshold. With the 4-dose standard regimen, >90% maintained concentrations >MIC beyond 48 hours. With the 2-dose regimen, newborns maintained the mean concentration >MIC within the 48-hour culture window and below neurotoxicity level. Infants 22–24 weeks’ gestation had higher drug concentrations and more prolonged exposure duration than 25–27 weeks’ gestation. CONCLUSIONS: For EOS in preterm infants, two ampicillin doses (50mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.
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spelling pubmed-92627542022-08-24 Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship Le, Jennifer Greenberg, Rachel G. Yoo, YoungJun Clark, Reese H. Benjamin, Daniel K. Zimmerman, Kanecia O. Cohen-Wolkowiez, Michael Wade, Kelly C. J Perinatol Article OBJECTIVE: Define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. STUDY DESIGN: We simulated ampicillin concentrations in newborns (birthweight<1500g; gestational age 22–27 weeks), summarizing three 48-hour regimens: high 100mg/kg Q8hr, medium 100mg/kg Q12hr, and standard 50mg/kg Q12hr. Concentration data were analyzed for concentration above minimum inhibitory concentration (MIC), below neurotoxicity threshold (C(max)≤140mcg/mL), and duration limited to 48 hours. RESULTS: Among 34,689 newborns, all dosing regimens provided concentrations above MIC through 48 hours, but C(max) exceeded the neurotoxicity threshold. With the 4-dose standard regimen, >90% maintained concentrations >MIC beyond 48 hours. With the 2-dose regimen, newborns maintained the mean concentration >MIC within the 48-hour culture window and below neurotoxicity level. Infants 22–24 weeks’ gestation had higher drug concentrations and more prolonged exposure duration than 25–27 weeks’ gestation. CONCLUSIONS: For EOS in preterm infants, two ampicillin doses (50mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity. 2022-07 2022-02-24 /pmc/articles/PMC9262754/ /pubmed/35210541 http://dx.doi.org/10.1038/s41372-022-01344-2 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Le, Jennifer
Greenberg, Rachel G.
Yoo, YoungJun
Clark, Reese H.
Benjamin, Daniel K.
Zimmerman, Kanecia O.
Cohen-Wolkowiez, Michael
Wade, Kelly C.
Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title_full Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title_fullStr Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title_full_unstemmed Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title_short Ampicillin Dosing in Premature Infants for Early-onset Sepsis: Exposure-driven Efficacy, Safety, and Stewardship
title_sort ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262754/
https://www.ncbi.nlm.nih.gov/pubmed/35210541
http://dx.doi.org/10.1038/s41372-022-01344-2
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