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Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach

ACOG Committee Opinion #797 proposed intrapartum vancomycin dosing guidelines in the absence of thorough evaluation of its risk versus benefit profile on the maternal and neonatal systems. The previously published serum and cord-blood concentration–time data of vancomycin given to mothers in the int...

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Autores principales: Farkas, Andras, Yassin, Arsheena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854597/
https://www.ncbi.nlm.nih.gov/pubmed/36671234
http://dx.doi.org/10.3390/antibiotics12010032
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author Farkas, Andras
Yassin, Arsheena
author_facet Farkas, Andras
Yassin, Arsheena
author_sort Farkas, Andras
collection PubMed
description ACOG Committee Opinion #797 proposed intrapartum vancomycin dosing guidelines in the absence of thorough evaluation of its risk versus benefit profile on the maternal and neonatal systems. The previously published serum and cord-blood concentration–time data of vancomycin given to mothers in the intrapartum period was analyzed in this work with a two-compartment pharmacokinetic (PK) model. Monte Carlo simulation was used to establish exposure for the studied population for doses of 1000 mg to 2000 mg every 8 h for gestational ages (GA) of 33 to 40 weeks and for birth times up to 4-h intervals. Probabilities of target attainment (PTA) were calculated for efficacy and toxicity indices unique to the peripartum maternal and neonatal population. Neonatal evaluations indicate uniformly high PTAs for the evaluated dosing regimens when the efficacy target is considered. On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA below 36 weeks and birth times beyond 20 h after the initiation of intrapartum prophylaxis and with doses greater than 1250 mg. Maternal vancomycin exposures seem reasonable up to two intrapartum doses given at 8 h intervals when the dose is kept to 1250 mg or less. Most mothers (up to 83%) who receive three or more doses of the commonly administered regimens are subjected to nephrotoxic exposures. Thus, it appears that the current recommendations by #797 for dosing of vancomycin pose considerable risk to mother and newborn alike, especially in cases with lengthy duration of preterm labor. Capping of doses at 1250 mg may be considered to minimize the need for therapeutic drug monitoring (TDM) interventions. Alternatively, and irrespective of the baseline maternal renal function, TDM for all cases requiring more than two doses of 1500 mg or higher must be assured.
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spelling pubmed-98545972023-01-21 Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach Farkas, Andras Yassin, Arsheena Antibiotics (Basel) Article ACOG Committee Opinion #797 proposed intrapartum vancomycin dosing guidelines in the absence of thorough evaluation of its risk versus benefit profile on the maternal and neonatal systems. The previously published serum and cord-blood concentration–time data of vancomycin given to mothers in the intrapartum period was analyzed in this work with a two-compartment pharmacokinetic (PK) model. Monte Carlo simulation was used to establish exposure for the studied population for doses of 1000 mg to 2000 mg every 8 h for gestational ages (GA) of 33 to 40 weeks and for birth times up to 4-h intervals. Probabilities of target attainment (PTA) were calculated for efficacy and toxicity indices unique to the peripartum maternal and neonatal population. Neonatal evaluations indicate uniformly high PTAs for the evaluated dosing regimens when the efficacy target is considered. On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA below 36 weeks and birth times beyond 20 h after the initiation of intrapartum prophylaxis and with doses greater than 1250 mg. Maternal vancomycin exposures seem reasonable up to two intrapartum doses given at 8 h intervals when the dose is kept to 1250 mg or less. Most mothers (up to 83%) who receive three or more doses of the commonly administered regimens are subjected to nephrotoxic exposures. Thus, it appears that the current recommendations by #797 for dosing of vancomycin pose considerable risk to mother and newborn alike, especially in cases with lengthy duration of preterm labor. Capping of doses at 1250 mg may be considered to minimize the need for therapeutic drug monitoring (TDM) interventions. Alternatively, and irrespective of the baseline maternal renal function, TDM for all cases requiring more than two doses of 1500 mg or higher must be assured. MDPI 2022-12-25 /pmc/articles/PMC9854597/ /pubmed/36671234 http://dx.doi.org/10.3390/antibiotics12010032 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Farkas, Andras
Yassin, Arsheena
Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title_full Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title_fullStr Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title_full_unstemmed Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title_short Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach
title_sort sorting out the risks and benefits of the #797 recommended intrapartum vancomycin dosing approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854597/
https://www.ncbi.nlm.nih.gov/pubmed/36671234
http://dx.doi.org/10.3390/antibiotics12010032
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