OBJECTIVES: To predict the appropriate dosing of intravenous fosfomycin for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in continuous renal replacement therapy (CRRT) patients.

METHODS: Minimum inhibitory concentration (MIC) values of all isolates were determined by E-test method. Population pharmacokinetic parameters were obtained from a previously published study. The percentages of a 24-hour period in which the drug concentration exceeded the MIC (%T>MIC) were defined to be 70% T>MIC and 100% T>MIC, respectively. In addition, the 24-hour area under the unbound concentration-time curve over the MIC (AUC_0-24/MIC) of 45 mg∙h/L was used as a target value. All dosing regimens were estimated for the probability of target attainment (PTA) using a Monte Carlo simulation.

RESULTS: For the effluent rate of 20 mL/kg/h, the PTA for reaching 70% T>MIC, 100% T>MIC, and AUC_0-24/MIC of 45 mg∙h/L was achieved in pathogens with a MIC of 24 mg/L, 12 mg/L, and 24 mg/L in all regimens, respectively. Meanwhile for the effluent rate of 25 mL/kg/h, the PTA for reaching 70% T>MIC, 100% T>MIC, and AUC_0-24/MIC of 45 mg∙h/L was achieved in organisms with a MIC of 16 mg/L, 12 mg/L and 24 mg/L in all regimens, respectively.

CONCLUSIONS: The appropriate fosfomycin dosing regimens for CRE infections in critically ill patients receiving CRRT were suggested based on pharmacokinetic/pharmacodynamic targets, MIC values, and effluent rates. Clinical validation is warranted.