In vitro antibacterial activity of fosfomycin combined with other antimicrobials against KPC-producing Klebsiella pneumoniae

- Data on possible synergy of fosfomycin (FM) with other antimicrobials are inconsistent.
- FM combined with five antimicrobials showed a significant additive effect against KPC-producing Klebsiella pneumoniae.
- FM enhances the bactericidal activity of the five other antimicrobial agents.
- FM + amikacin could have great potential as a therapeutic option for KPC-producing K. pneumoniae.

The increasing prevalence of KPC-producing Klebsiella pneumoniae (KPC-Kp) strains poses a serious threat to patients. Therapeutic options are limited to colistin, fosfomycin, tigecycline and selected aminoglycosides. Although the combination of fosfomycin with other antimicrobials is recommended, data regarding possible synergistic activity in vitro and in vivo appear inconsistent. Here we report that five drug combinations (fosfomycin combined with imipenem, ertapenem, tigecycline, colistin or amikacin) had a significant additive effect against 136 KPC-Kp strains in an in vitro chequerboard assay. In addition, time-kill assays revealed that fosfomycin enhanced the bactericidal activity of the five other antimicrobial agents. Moreover, owing to its persistent bactericidal effect, the combination of fosfomycin plus amikacin is an effective therapeutic candidate for infections by KPC-producing organisms.