Work

A reappraisal of carbapenems dosing in febrile neutropenic patients

Year: 2025

Type: article

Abstract: • This study highlights that label dosages of carbapenems with a 0.5-hour infusion failed to achieve the PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for Enterobacteriales in febrile neutropenic patients. • The findings emphasize that increasing the dose did not consistently ensure improved probability of PK/PD target attainment for carbapenems. However, extending the infusion duration to 3 hours consistently increased the likelihood of achieving the PK/PD target. • The study confirms that a one-size-fits-all approach to carbapenem dosing is inadequate. Individualized dosing strategies, informed by patient-specific pharmacokinetic parameters such as creatinine clearance, body weight, as well as the MIC value of the identified pathogen, should be prioritized. 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. 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%. 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-hour 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 hours or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target. Standard carbapenem dosing with 0.5-hour infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.

Source: Journal of Global Antimicrobial Resistance

DOI: 10.1016/j.jgar.2025.10.006