• Taniya Charoensareerat, Phongphak Bunrit, Sasina Phanpoka, Thananya Netthanomsak, Dhakrit Rungkitwattanakul, Sutthiporn Pattharachayakul, Nattachai Srisawat, and Weerachai Chaijamorn.
• Faculty of Pharmacy, Siam University, Bangkok, Thailand.
• J Crit Care. 2025 Feb 1; 85: 154946154946.

PurposeTo 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 MethodsA 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.ResultsThe 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.ConclusionsDosing 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.Copyright © 2024 Elsevier Inc. All rights reserved.

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