Activity of antimicrobial combinations against KPC-2-producing Klebsiella pneumoniae in a rat model and time-kill assay

Antimicrob Agents Chemother. 2015 Jul;59(7):4301-4. doi: 10.1128/AAC.00323-15. Epub 2015 Apr 20.

Abstract

This study evaluated the efficacy of tigecycline (TIG), polymyxin B (PMB), and meropenem (MER) in 80 rats challenged with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae infection. A time-kill assay was performed with the same strain. Triple therapy and PMB+TIG were synergistic, promoted 100% survival, and produced negative peritoneal cultures, while MER+TIG showed lower survival and higher culture positivity than other regimens (P = 0.018) and was antagonistic. In vivo and in vitro studies showed that combined regimens, except MER+TIG, were more effective than monotherapies for this KPC-producing strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Ascitic Fluid / microbiology
  • Colony Count, Microbial
  • Drug Combinations
  • Drug Interactions
  • Drug Synergism
  • Female
  • Kaplan-Meier Estimate
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / microbiology*
  • Klebsiella Infections / mortality
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Male
  • Microbial Sensitivity Tests
  • Rats
  • Rats, Wistar
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • beta-lactamase KPC-2
  • beta-Lactamases