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

Int J Antimicrob Agents. 2017 Aug;50(2):237-241. doi: 10.1016/j.ijantimicag.2017.03.011. Epub 2017 Jun 22.

Abstract

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.

Keywords: Bactericidal effect; Combination therapy; Fosfomycin; KPC-producing Klebsiella pneumoniae; Synergistic effect.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Synergism*
  • Fosfomycin / pharmacology*
  • Humans
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology*
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Fosfomycin
  • beta-Lactamases