Population pharmacokinetic/pharmacodynamic target attainment analysis of IV fosfomycin for the treatment of MDR Gram-negative bacterial infections.

This article focuses on determining optimal intravenous (IV) fosfomycin dosing regimens for patients with multidrug-resistant (MDR) Gram-negative bacterial infections across varying levels of kidney function. Using population pharmacokinetic (PK) modeling and Monte Carlo simulations in 24 Thai patients, the study found that creatinine clearance (eCLCR) and gender significantly influence fosfomycin clearance. It proposes kidney function-adjusted dosing regimens, recommending 15 g/day for patients with normal kidney function (eCLCR 91–120 mL/min) to achieve ≥90% probability of target attainment (PTA) against Escherichia coli and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) ≤32 mg/L. The study also notes that higher doses may be necessary for Pseudomonas aeruginosa, though safety data are limited, and highlights a notable incidence of hypernatraemia associated with fosfomycin therapy, especially in patients with impaired kidney function or higher doses. These findings suggest that lower fosfomycin dosages than currently practiced may improve tolerability while maintaining efficacy, but clinical validation is needed.