Reduced susceptibility to chlorhexidine among extremely-drug-resistant strains of Klebsiella pneumoniae

J Hosp Infect. 2012 May;81(1):15-9. doi: 10.1016/j.jhin.2012.02.007. Epub 2012 Mar 30.


Background: Over the last decade, extremely-drug-resistant (XDR) strains of Klebsiella pneumoniae have emerged worldwide, mainly as a result of patient-to-patient spread. The predominant clone, sequence type 258 (ST258), is associated with high morbidity and mortality, and is a worldwide threat to public health. It was hypothesized that reduced susceptibility to chlorhexidine, the most widely used hospital disinfectant, may contribute to the endemic nature of this strain.

Aim: To characterize and compare the susceptibility of the epidemic K. pneumoniae clone ST258 and non-epidemic K. pneumoniae clones to chlorhexidine.

Methods: The minimum inhibitory concentration (MIC) of chlorhexidine was determined in 126 XDR K. pneumoniae clinical isolates using agar dilution. Expression of three different efflux pumps -cepA, acrA and kdeA - was investigated in the absence and presence of chlorhexidine using quantitative real-time polymerase chain reaction. Heteroresistance to chlorhexidine was identified using population analysis.

Findings: The MIC of chlorhexidine was higher for K. pneumoniae ST258 (N = 70) than other K. pneumoniae sequence types (N = 56); 99% of ST258 isolates had MICs >32 μg/mL, compared with 52% of other K. pneumoniae sequence types (P < 0.0001). Reduced susceptibility to chlorhexidine appeared to be independent of the expression of cepA, acrA and kdeA efflux pumps. Chlorhexidine-resistant subpopulations were observed independent of the bacterial sequence type or the MIC.

Conclusions: Reduced susceptibility to chlorhexidine may contribute to the success of XDR K. pneumoniae as a nosocomial pathogen, and may provide a selective advantage to the international epidemic strain K. pneumoniae ST258. The heterogeneous nature of chlorhexidine-resistant subpopulations suggests that this phenomenon might not be rendered genetically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Chlorhexidine / pharmacology*
  • Cross Infection / microbiology
  • Disinfectants / pharmacology*
  • Drug Resistance, Multiple, Bacterial*
  • Gene Expression Profiling
  • Humans
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / isolation & purification
  • Microbial Sensitivity Tests / methods
  • Real-Time Polymerase Chain Reaction


  • Bacterial Proteins
  • Disinfectants
  • Chlorhexidine