Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use

PLoS One. 2010 Feb 16;5(2):e9233. doi: 10.1371/journal.pone.0009233.

Abstract

Background: Trimethoprim resistance is increasing in Enterobacteriaceae. In 2004-2006 an intervention on trimethoprim use was conducted in Kronoberg County, Sweden, resulting in 85% reduction in trimethoprim prescriptions. We investigated the distribution of dihydrofolate reductase (dfr)-genes and integrons in Escherichia coli and Klebsiella pneumoniae and the effect of the intervention on this distribution.

Methodology/principal findings: Consecutively isolated E. coli (n = 320) and K. pneumoniae (n = 54) isolates phenotypically resistant to trimethoprim were studied. All were investigated for the presence of dfrA1, dfrA5, dfrA7, dfrA8, dfrA12, dfrA14, dfrA17 and integrons class I and II. Isolates negative for the seven dfr-genes (n = 12) were also screened for dfr2d, dfrA3, dfrA9, dfrA10, dfrA24 and dfrA26. These genes accounted for 96% of trimethoprim resistance in E. coli and 69% in K. pneumoniae. The most prevalent was dfrA1 in both species. This was followed by dfrA17 in E. coli which was only found in one K. pneumoniae isolate. Class I and II Integrons were more common in E. coli (85%) than in K. pneumoniae (57%). The distribution of dfr-genes did not change during the course of the 2-year intervention.

Conclusions/significance: The differences observed between the studied species in terms of dfr-gene and integron prevalence indicated a low rate of dfr-gene transfer between these two species and highlighted the possible role of narrow host range plasmids in the spread of trimethoprim resistance. The stability of dfr-genes, despite large changes in the selective pressure, indirectly suggests a low fitness cost of dfr-gene carriage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents, Urinary / pharmacology
  • Anti-Infective Agents, Urinary / therapeutic use
  • Bacterial Proteins / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / isolation & purification
  • Gene Frequency
  • Genotype
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / epidemiology
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Integrons / genetics
  • Isoenzymes / genetics
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / isolation & purification
  • Phenotype
  • Sweden / epidemiology
  • Tetrahydrofolate Dehydrogenase / genetics
  • Trimethoprim / pharmacology*
  • Trimethoprim / therapeutic use
  • Trimethoprim Resistance / genetics*
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / epidemiology
  • Urinary Tract Infections / microbiology

Substances

  • Anti-Infective Agents, Urinary
  • Bacterial Proteins
  • Isoenzymes
  • Trimethoprim
  • Tetrahydrofolate Dehydrogenase