Activity of the colistin-rifampicin combination against colistin-resistant, carbapenemase-producing Gram-negative bacteria

J Chemother. 2014 Aug;26(4):211-6. doi: 10.1179/1973947813Y.0000000136. Epub 2013 Dec 6.

Abstract

Colistin (COL) is one of the few antimicrobials that retain activity against carbapenemase-producing Gram-negative bacteria (GNB). However, the emergence of COL resistance has renewed the use of combination therapy. The aim of this study was to determine the activity of COL plus rifampicin (RIF) against clinical isolates of COL-resistant, carbapenemase-producing GNB. We employed 36 COL-resistant carbapenemase-producing isolates (27 Klebsiella pneumoniae, 5 Serratia marcescens, and 4 Acinetobacter baumannii) belonging to 36 patients. E-test/agar dilution of all strains was performed with E-test strips of COL placed on agar plates with and without RIF. In 11 patients, the synergy was confirmed by time-kill studies. Synergy was detected in 34 isolates, whereas indifference was detected in two S. marcescens. The E-test/agar dilution method showed comparable results to the time-kill studies. Seven patients infected with these isolates (two meningitis, four sepsis, and one urinary tract infection) were treated with the combination successfully.

Keywords: Carbapenemase,; Colistin resistance,; Combination studies,; Gram-negative bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / enzymology
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism*
  • Colistin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial* / drug effects
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacteria / isolation & purification
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / isolation & purification
  • Microbial Sensitivity Tests
  • Rifampin / pharmacology*
  • Serratia marcescens / drug effects
  • Serratia marcescens / enzymology
  • Serratia marcescens / isolation & purification
  • Structure-Activity Relationship
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase
  • Rifampin
  • Colistin