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Model-informed precision dosing of linezolid for the treatment of diabetic foot infections
Xu-Ben Yu1, Chuang Chen1,2, Rui-Yun Ling1,2
1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Aims:
The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of linezolid in patients with diabetic foot infections (DFIs) remain insufficiently characterized. This study aimed to develop a population PK model, optimize dosing regimens and establish individualized dosing software for linezolid.
Methods:
Clinical characteristics, microbiological data and linezolid concentrations were retrospectively collected from 88 patients with DFIs, comprising 173 linezolid plasma concentrations and 247 microbial isolates. Population PK modelling and Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) and cumulative fraction of response (CFR). The final model was integrated into individualized dosing software.
Results:
Linezolid pharmacokinetics were best described by a one-compartment model with first-order elimination. The typical clearance (CL) and volume of distribution (V) were 1.69 L/h and 17.4 L, respectively, with creatinine clearance (CrCL) identified as the primary covariate on CL. For isolates with MIC ≤2 μg/mL, simulations suggested 400 mg q12h for patients with CrCL ≤30 mL/min and 600 mg q12h for those with CrCL ≥30 mL/min. A regimen of 600 mg q12h achieved CFR ≥90% for major pathogens, including Staphylococcus aureus, Streptococcus agalactiae and Enterococcus faecalis, while 600 mg q24h was sufficient for Staphylococcus lugdunensis. The individualized dosing software demonstrated good agreement between observed and predicted concentrations.
Conclusions:
Renal function significantly affects linezolid pharmacokinetics in patients with DFIs. This study provides model-informed dosing strategies and a validated tool to support individualized linezolid therapy.
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