Oral fosfomycin treatment for enterococcal urinary tract infections in a dynamic in vitro model

There are limited treatment options for enterococcal urinary tract infections, especially vancomycin-resistant (VRE). Oral fosfomycin is a potential option, although limited data are available guiding dosing and susceptibility. We undertook pharmacodynamic profiling of fosfomycin against and isolates using a dynamic bladder infection model. Eighty-four isolates underwent fosfomycin agar dilution susceptibility testing ( MIC 32/64 μg/mL; MIC 64/128 μg/mL). Sixteen isolates (including ATCC 29212 and ATCC 35667) were chosen to reflect the MIC range and tested in the bladder infection model with synthetic human urine (SHU). Under drug-free conditions, demonstrated greater growth restriction in SHU compared to ( maximal growth 5.8 ± 0.6 log CFU/mL; 8.0 ± 1.0 log CFU/mL). Isolates were exposed to high and low fosfomycin urinary concentrations after a single dose, and two-doses given daily with low urinary exposure. Simulated concentrations closely matched the target (bias 2.3%). isolates required greater fosfomycin exposure for 3 log kill from the starting inoculum compared with The AUC/MIC and %T > MIC for was 672 and 70%, compared to 216 and 51% for respectively. There was no rise in fosfomycin MIC post-exposure. Two doses of fosfomycin with low urinary concentrations resulted in equivalent growth inhibition to a single dose with high urinary concentrations. With this urinary exposure, fosfomycin was effective in promoting suppression of regrowth (>3 log kill) in the majority of isolates