In vitro investigation of synergy among fosfomycin and parenteral antimicrobials against carbapenemase-producing Enterobacteriaceae.

Intravenous fosfomycin is undergoing clinical development in the United States for treatment of complicated urinary tract infections (cUTIs) and may be prescribed as a component of dual antibiotic regimens against carbapenemase-producing Enterobacteriaceae (CPE). Fosfomycin, aztreonam, cefepime, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, piperacillin/tazobactam, and tobramycin minimum inhibitory concentrations (MICs) were determined by gradient diffusion strip (GDS) against CPE isolates (N = 49). The GDS cross method was used to assess antibiotic interactions between fosfomycin and the aforementioned parenteral antibiotics. The resultant fractional inhibitory concentration index was used to classify interactions. Fosfomycin-containing combinations were evaluated only if nonsusceptible to the second agent. The fosfomycin MIC was ≥1024 mg/L by GDS. Synergy or additivity was detected in 80 (22%) fosfomycin-containing combinations. Antagonism was not observed. Ceftolozane/tazobactam most frequently displayed synergy [8 (16.3%) isolates]. When CPE are isolated, clinical laboratories should consider performing GDS synergy tests to identify favorable antibiotic interactions.