Determination of synergy between sulbactam, meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance

J Chemother. 2016 Aug;28(4):297-303. doi: 10.1080/1120009X.2016.1143261.

Abstract

Treatment of infections with carbapenem-resistant Gram negative organism is a major challenge especially among intensive care patients. Combinations of sulbactam, meropenem and colistin was studied for its synergistic activity against 100 invasive isolates of carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii-calcoaceticus complex by checkerboard assay and time kill assay (TKA). In addition, presence of carbapenemase production was determined by multiplex PCR. Time kill assay detected more synergy than checkerboard assay. Good bactericidal activity of 70-100% was noted with the combinations tested. Among K. pneumoniae, isolates producing NDM carbapenemase alone showed significantly more synergy than isolates producing OXA-48-like carbapenemases. In treatment of infection with carbapenem-resistant organisms, the site of infection and the type of carbapenemase produced may help to determine the most effective combination of antimicrobials.

Keywords: Acinetobacter baumannii; Carbapenem resistant; Colistin; OXA-48 like; Klebsiella pneumoniae; Meropenem; NDM; Sulbactam; Synergy.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Carbapenems / pharmacology*
  • Colistin / pharmacology
  • Drug Resistance, Bacterial / genetics
  • Drug Synergism
  • Humans
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / isolation & purification
  • Meropenem
  • Microbial Sensitivity Tests
  • Sulbactam / pharmacology
  • Thienamycins / pharmacology
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Thienamycins
  • beta-Lactamases
  • carbapenemase
  • Meropenem
  • Sulbactam
  • Colistin