In vitro interactions of antimicrobial combinations with fosfomycin against KPC-2-producing Klebsiella pneumoniae and protection of resistance development

Antimicrob Agents Chemother. 2011 May;55(5):2395-7. doi: 10.1128/AAC.01086-10. Epub 2011 Feb 14.

Abstract

Using time-kill methodology, we investigated the interactions of fosfomycin with meropenem or colistin or gentamicin against 17 genetically distinct Klebsiella pneumoniae clinical isolates carrying blaKPC-2. Synergy was observed with meropenem or colistin against 64.7 and 11.8% of tested isolates, while the combination with gentamicin resulted in indifference. All studied combinations showed improved bactericidal activity, compared to fosfomycin alone and prevented the development of fosfomycin resistance in 69.2, 53.8, and 81.8% of susceptible isolates, respectively.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Colistin / pharmacology
  • Drug Resistance, Multiple, Bacterial
  • Drug Synergism
  • Fosfomycin / pharmacology*
  • Gentamicins / pharmacology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / genetics
  • Meropenem
  • Microbial Sensitivity Tests
  • Thienamycins / pharmacology
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Anti-Infective Agents
  • Gentamicins
  • Thienamycins
  • Fosfomycin
  • beta-lactamase KPC-2
  • beta-Lactamases
  • Meropenem
  • Colistin