Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function

Abstract Fosfomycin has been used to treat carbapenem‐resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different do...

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Main Authors: Nattapong Tidwong, Anan Chanruang, Suthanya Chupradit, Suzanne L. Parker, Pannee Leelawattanachai, Poramed Winichakoon, Baralee Punyawudho
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.70038
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author Nattapong Tidwong
Anan Chanruang
Suthanya Chupradit
Suzanne L. Parker
Pannee Leelawattanachai
Poramed Winichakoon
Baralee Punyawudho
author_facet Nattapong Tidwong
Anan Chanruang
Suthanya Chupradit
Suzanne L. Parker
Pannee Leelawattanachai
Poramed Winichakoon
Baralee Punyawudho
author_sort Nattapong Tidwong
collection DOAJ
description Abstract Fosfomycin has been used to treat carbapenem‐resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.
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spelling doaj-art-79ac0281614249c4875c3515056b13fb2025-08-20T02:11:11ZengWileyClinical and Translational Science1752-80541752-80622024-10-011710n/an/a10.1111/cts.70038Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal functionNattapong Tidwong0Anan Chanruang1Suthanya Chupradit2Suzanne L. Parker3Pannee Leelawattanachai4Poramed Winichakoon5Baralee Punyawudho6Department of Pharmaceutical Care, Faculty of Pharmacy Chiang Mai University Chiang Mai ThailandDepartment of Pharmaceutical Care, Faculty of Pharmacy Chiang Mai University Chiang Mai ThailandDepartment of Pharmaceutical Care, Faculty of Pharmacy Chiang Mai University Chiang Mai ThailandThe University of Queensland Centre for Clinical Research The University of Queensland Brisbane Queensland AustraliaDepartment of Pharmacy, Faculty of Medicine Vajira Hospital Navamindradhiraj University Bangkok ThailandDivision of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine Chiang Mai University Chiang Mai ThailandDepartment of Pharmaceutical Care, Faculty of Pharmacy Chiang Mai University Chiang Mai ThailandAbstract Fosfomycin has been used to treat carbapenem‐resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.https://doi.org/10.1111/cts.70038
spellingShingle Nattapong Tidwong
Anan Chanruang
Suthanya Chupradit
Suzanne L. Parker
Pannee Leelawattanachai
Poramed Winichakoon
Baralee Punyawudho
Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
Clinical and Translational Science
title Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
title_full Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
title_fullStr Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
title_full_unstemmed Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
title_short Optimized fosfomycin regimens for treating carbapenem‐resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
title_sort optimized fosfomycin regimens for treating carbapenem resistant acinetobacter baumannii in critically ill patients with varying degrees of renal function
url https://doi.org/10.1111/cts.70038
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