Synergistic activity of polymyxin B combined with vancomycin against carbapenem-resistant and polymyxin-resistant Acinetobacter baumannii: first in vitro study

J Med Microbiol. 2019 Mar;68(3):309-315. doi: 10.1099/jmm.0.000920. Epub 2019 Jan 21.

Abstract

Purpose: The effect of a combination of polymyxin B (PMB) and vancomycin (VAN) was assessed against six Acinetobacter baumannii clinical isolates belonging to six different clusters (three PMB-susceptible and three PMB-resistant).

Methodology: The synergistic effect of the PMB-VAN combination was determined with the checkerboard, time-kill, disk-diffusion and M.I.C.Evaluator assays. PMB-resistance was investigated with mcr-1 gene amplification and a mutant frequency assay.

Results: In the checkerboard assay, all PMB-resistant isolates showed a synergistic effect. The time-kill assay demonstrated that the PMB-VAN combination had a bactericidal effect at 24 h against isolates with a high mutant rate for PMB, suggesting that this combination may block the hypermutation of some isolates. No antagonism was detected. All PMB-resistant isolates also showed synergism in the disk-diffusion test, and a significant decrease in VAN MICs in the M.I.C.Evaluator assay.

Conclusion: Our findings indicate that the PMB-VAN combination has a synergistic effect on A. baumannii, especially against PMB-resistant isolates.

Keywords: Acinetobacter baumannii; drug combinations; polymyxin B; vancomycin.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Synergism
  • Humans
  • Microbial Sensitivity Tests
  • Polymyxin B / pharmacology*
  • Vancomycin / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Vancomycin
  • Polymyxin B