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 bla _IMP. bla _VIM. bla _NDM. bla _OXA-48 like, bla _KPC. bla _GES.#x00A0;and bla _SPM. 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.