In vitro activity of imipenem-relebactam alone and in combination with fosfomycin against carbapenem-resistant gram-negative pathogens

The aim of this study was to investigate in vitro activity of imipenem-relebactam alone and in combination with fosfomycin against carbapenem-resistant Gram-negative pathogens. A total of 100 Gram-negative bacteria resistant to carbapenem were collected. Among collected 25 carbapenem-resistant Klebsiella pneumoniae strains, 24 (96%) were KPC producers and none of them displayed NDM-1, NDM-5, and IMP carbapenemase. Among 25 carbapenem-resistant Escherichia coli strains, 3(12%), 1(4%), 17(68%), 25(100%) and 20(80%) harbored KPC, NDM-1, NDM-5, ESBLs, and membrane porin OmpC or OmpF mutations, respectively. Among all the carbapenem-resistant strains, 40% (40/100) were resistant to imipenem-relebactam. The FICI revealed the synergistic (60%, 6/10) and additive (40%, 4/10) effects of imipenem-relebactam in combination with fosfomycin, wherein synergistic activity was found against all tested Klebsiella pneumoniae and Acinetobacter baumannii. Imipenem-relebactam may be a new alternative for carbapenem-resistant Gram-negative pathogens infections and the combination of imipenem-relebactam and fosfomycin warrants further exploration.