Fosfomycin Dosing Regimens based on Monte Carlo Simulation for Treated Carbapenem-Resistant

backgroundInfections by Carbapenem-Resistant MATERIALS AND

methodsFosfomycin MIC was defined by the E-test method. We used Fosfomycin pharmacokinetic parameters from a previously published study. The percent of the time period in which the drug concentration exceeded the MIC, or %T>MIC, used in this study were determined to be 70% of T>MIC and 100% of T>MIC, respectively. All dosing regimens were estimated for the probability of target attainment using a Monte Carlo simulation.

resultsIn this study, we found the MIC's of fosfomycin against CRE isolates ranged from 8 mg/L to 96 mg/L. The total daily dose of fosfomycin ranged from 16 - 24 g and was administered utilizing various fosfomycin dosing regimens to achieve the pharmacokinetic/pharmacodynamic (PK/PD) target in pathogens with a MIC of 32 mg/L for 70%T>MIC and a MIC of 12 mg/L for 100%T>MIC, respectively. For the twelve patients who received the recommended fosfomycin dosing regimen, eleven achieved bacterial eradication for a microbiological cure rate of 91%; and of those patients achieving eradication, two died despite having negative cultures for CRE; the one remaining patient had bacterial persistence. The most commonly observed adverse drug reactions were hypernatremia (3 cases) and hypokalemia (3 cases) and acute kidney injury (3 cases).

conclusionOur findings suggest fosfomycin has tended to good efficacy when using dosing regimens that achieve the PK/PD target. Nonetheless, further validation of these regimens in larger populations is needed.