Lipopeptide Paenipeptin Analogues Potentiate Clarithromycin and Rifampin against Carbapenem-Resistant Pathogens

Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00329-18. doi: 10.1128/AAC.00329-18. Print 2018 Aug.

Abstract

Two paenipeptin analogues at 4 μg/ml potentiated clarithromycin and rifampin against carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains. The combined treatment significantly increased their antibacterial efficacy in a microbiological medium and in human serum in vitro at therapeutically relevant concentrations. Moreover, these two paenipeptin analogues showed low cytotoxicity against a human kidney cell line. Therefore, combination therapy with paenipeptins may be an option for the treatment of antibiotic-resistant bacterial infections.

Keywords: clarithromycin; combination therapy; lipopeptide; paenipeptin; rifampin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / growth & development
  • Acinetobacter baumannii / pathogenicity
  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / pharmacology
  • Cell Survival / drug effects
  • Clarithromycin / pharmacology*
  • Drug Combinations
  • Drug Synergism
  • HEK293 Cells
  • Humans
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / growth & development
  • Klebsiella pneumoniae / pathogenicity
  • Lipopeptides / chemical synthesis
  • Lipopeptides / pharmacology*
  • Microbial Sensitivity Tests
  • Rifampin / pharmacology*
  • beta-Lactam Resistance / drug effects

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Drug Combinations
  • Lipopeptides
  • Clarithromycin
  • Rifampin