Prevalence of in vitro synergistic antibiotic interaction between fosfomycin and nonsusceptible antimicrobials in carbapenem-resistant Pseudomonas aeruginosa

We assessed the synergistic potential of fosfomycin and parenteral antibiotics among carbapenem-resistant Pseudomonas aeruginosa (CRP).Minimum inhibitory concentrations (MICs) were determined by broth microdilution for all antibiotics except fosfomycin, for which the gradient diffusion strip (GDS) method was used. The GDS cross method was performed to assess interactions between fosfomycin and: aztreonam, cefepime, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, piperacillin/tazobactam and tobramycin. Only organisms that were nonsusceptible to the second drug were assessed.Among 153 clinical isolates, the fosfomycin MIC50/90 was 48/≥1024 mg l-1 . Synergy was detected in 131/604 (21.7 %) fosfomycin-antibiotic combinations among 76 (49.7 %) isolates. Ceftazidime (42/81, 51.9%) and ceftolozane/tazobactam (7/14, 50.0%) displayed synergy most frequently. Meropenem susceptibility was restored in 21 (13.7 %) isolates. Antagonism was not observed.Fosfomycin synergy was commonly observed in vitro among CRP. These data may guide the selection of combination antibiotic therapy. The susceptibility to other antibiotics was restored in combination with fosfomycin, warranting further in vivo evaluation.