Journal of global antimicrobial resistance · 2025
A reappraisal of carbapenems dosing in febrile neutropenic patients.
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Qin Sun-Ting, Kong Meng-Yu, Ling Rui-Yun, Fu Jing, Chen Yao-Jie, Zeng Yu-Han, Jiang Dan-Na, Zhang Xiu-Hua, Yu Xu-Ben, Zhang Hai-Na
Аннотация
OBJECTIVE: This study aims to optimize carbapenem dosing strategies in febrile neutropenic (FN) patients by evaluating the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) using Monte Carlo simulations based on published population PK (PopPK) models and real-world covariate data.
METHODS: A systematic review of published PopPK studies on carbapenems in FN patients was conducted to obtain relevant PK parameters. In parallel, retrospective clinical data from FN patients treated at the First Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2024 were collected to provide covariates for Monte Carlo simulation. Monte Carlo simulations were then performed to evaluate the PTA for various dosing regimens. Dosing regimens were assessed based on achieving a PTA of ≥ 90%.
RESULTS: A total of 96 studies were screened, of which 4 met the inclusion criteria. Separately, real-world covariate data were obtained from 163 FN patients to inform the Monte Carlo simulations. The simulation results showed that standard label dosages of carbapenems administered over 0.5-h infusions failed to consistently achieve a PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for Enterobacterales. Notably, increasing the dose did not consistently improve PTA, whereas extending the infusion duration to 3 h or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target.
CONCLUSION: Standard carbapenem dosing with 0.5-h infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.
METHODS: A systematic review of published PopPK studies on carbapenems in FN patients was conducted to obtain relevant PK parameters. In parallel, retrospective clinical data from FN patients treated at the First Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2024 were collected to provide covariates for Monte Carlo simulation. Monte Carlo simulations were then performed to evaluate the PTA for various dosing regimens. Dosing regimens were assessed based on achieving a PTA of ≥ 90%.
RESULTS: A total of 96 studies were screened, of which 4 met the inclusion criteria. Separately, real-world covariate data were obtained from 163 FN patients to inform the Monte Carlo simulations. The simulation results showed that standard label dosages of carbapenems administered over 0.5-h infusions failed to consistently achieve a PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for Enterobacterales. Notably, increasing the dose did not consistently improve PTA, whereas extending the infusion duration to 3 h or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target.
CONCLUSION: Standard carbapenem dosing with 0.5-h infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.