Emergence and dissemination of colistin-resistant Klebsiella pneumoniae isolates expressing OXA-48 plus CTX-M-15 in patients not previously treated with colistin in a Spanish university hospital

Diagn Microbiol Infect Dis. 2019 Feb;93(2):147-153. doi: 10.1016/j.diagmicrobio.2018.08.014. Epub 2018 Sep 8.

Abstract

Dissemination of multidrug-resistant Klebsiella pneumoniae in the hospital environment represents a primary target of resistance containment and stewardship programs. At present, polymyxins, mostly in combination, exemplify a last-resort alternative. Colistin-resistant K. pneumoniae isolates harboring OXA-48 plus CTX-M-15 (n = 21) with the simultaneous colistin-susceptible counterparts (n = 9) were recovered from 14 hospitalized patients (January 2014-January 2015) admitted in different wards. In most cases, patients had not previously received colistin. Genetic relatedness experiments demonstrated that 93% (28/30) of isolates belonged to the ST11 high-risk clone. Heteroresistance and the fitness cost of colistin resistance were addressed in susceptible and resistant isolates as well as in in vitro-obtained stable mutants, and results appeared to be strain dependent. Whole genome sequencing demonstrated molecular changes in pmrA, pmrB, and mgrB genes. Plasmid-mediated colistin resistance genes were not found. Colistin resistance in multidrug-resistant K. pneumoniae isolates should be continuously monitored to detect its potential emergence, even in patients not previously exposed to colistin.

Keywords: Colistin resistance; Fitness; Heteroresistance; Klebsiella pneumoniae; OXA-48.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Colistin / pharmacology*
  • Drug Resistance, Bacterial / genetics*
  • Female
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae* / drug effects
  • Klebsiella pneumoniae* / enzymology
  • Klebsiella pneumoniae* / genetics
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Spain
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

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