MATERIALS AND METHODS: Fosfomycin 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.

RESULTS: In 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).