Emergence of colistin resistance without loss of fitness and virulence after prolonged colistin administration in a patient with extensively drug-resistant Acinetobacter baumannii

Diagn Microbiol Infect Dis. 2015 Jul;82(3):222-6. doi: 10.1016/j.diagmicrobio.2015.03.013. Epub 2015 Mar 25.

Abstract

The spread of extensively drug-resistant (XDR) gram-negative bacteria has boosted colistin use, with a resultant selection of colistin-resistant, often pandrug-resistant strains. Whether acquisition of further resistance mechanisms translates into a reduced virulence is the subject of active research. In this report, we describe clinical features of an immunocompromised patient who developed infection due to colistin-resistant Acinetobacter baumannii while on long-term colistin therapy. We analyzed phenotypic and genotypic characteristics, molecular mechanisms of colistin resistance, and in vitro and in vivo fitness of sequential colistin-sensitive and colistin-resistant strains isolated from the patient. Both colistin-sensitive and colistin-resistant strains were XDR and showed identical ST78 genotype. At variance with prior reports on colistin-resistant strains of A. baumannii, resistance to colistin due to P233S mutation in PmrB sensor kinase did not associate with any measurable reduction in strain fitness, growth characteristics, and virulence.

Keywords: Acinetobacter baumannii; Colistin resistance; Colistin therapy; In vitro fitness; In vivo virulence; pmrB mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / growth & development
  • Acinetobacter baumannii / pathogenicity
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Colistin / pharmacology*
  • Colistin / therapeutic use
  • DNA, Bacterial / genetics
  • Drug Resistance, Bacterial*
  • Female
  • Genotype
  • Humans
  • Immunocompromised Host
  • Male
  • Middle Aged
  • Mutation*
  • Transcription Factors / genetics
  • Virulence
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • PmrB protein, bacteria
  • Transcription Factors
  • Colistin