418. Fosfomycin Dosing Regimens for The Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Receiving Continuous Renal Replacement Therapy: a Monte Carlo Simulation

BACKGROUND: 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. CONCLUSION: 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. DISCLOSURES: All Authors: No reported disclosures.