Synergistic activity of fosfomycin-meropenem and fosfomycin-colistin against carbapenem resistant Klebsiella pneumoniae : An in vitro evidence

Abstract

Aim: To evaluate the antibacterial activity of fosfomycin-meropenem and fosfomycin-colistin combinations against carbapenem-resistant Klebsiella pneumoniae (CR-Kp). Methods: A total of 50 CR-Kp isolates recovered from blood cultures were included in this study. All the CR-Kp isolates were screened for the presence of carbapenem resistant genes blaIMP, blaVIM, blaNDM, blaOXA-48 like, blaKPC, blaGES and blaSPM. Combination testing of fosfomycin-meropenem and fosfomycin-colistin were performed using time-kill assay. Results: Fosfomycin-meropenem combination showed synergy in 20% of the tested CR-Kp isolates.While, fosfomycin-colistin exhibited synergy against 16% of the isolates. A total of 68% (n = 34) of CR-Kp isolates were characterised as OXA-48-like producers and 22% (n = 11) as NDM producers. Synergistic activity of these combinations was observed against OXA-48, NDM and NDM + OXA-48 co-producers. Conclusion: Considerable synergistic antibacterial activity of fosfomycin-meropenem and fosfomycin-colistin was not observed against CR-Kp isolates. Therefore, these combinations may not be promising for infections associated with CR-Kp. Lay abstract: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections are difficult to treat and are associated with a high mortality rate. This study aimed to evaluate the synergistic activity of fosfomycin-meropenem and fosfomycin-colistin combinations against CR-Kp. Synergistic activity of these combinations was observed against OXA-48, NDM and NDM + OXA-48 co-producers. However, synergism was not found to be significant. Therefore, these combinations may not be promising for infections associated with CR-Kp.