Optimizing fosfomycin dosing regimens in critically ill patients with and without continuous renal replacement therapy

Purpose

To define the optimal fosfomycin dosing regimens for drug-resistant gram-negative bacteria in critically ill patients and those receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulations.

Materials and methods

A pharmacokinetic model for patients with and without CRRT was created to predict fosfomycin deposition in these patients. The pharmacodynamics (PD) targets were AUC/MIC ratio > 21.5, 28.2, and 98.8 for drug-resistant Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA) and Escherichia coli (EC) infections, respectively. The optimal regimen was defined when the probability of target attainment (PTA) was >90 % of the virtual patients.

Results

The fosfomycin dosing regimens for KP infections with MIC 64 mg/L in critically ill patients and who received CRRT were 6 g every 8 h and 8 g every 12 h, respectively. For PA infections, the regimens of 6 g every 6 h and 7 g every 8 h achieved the target in critically ill patients and those undergoing CRRT. No regimen achieved the 90 % PTA against the EC infection with MIC >32 mg/L.

Conclusions

Dosing regimens for bacteria with high MICs as 64 mg/L in these patients were 18–24 g/day. Dose adjustments were required in those undergoing CRRT. Clinical validation is strongly needed.