title: Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden. alma.brolund@smi.se
authors.forename: Alma
authors.initials: A
authors.lastname: Brolund
authors.forename: Martin
authors.initials: M
authors.lastname: Sundqvist
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kahlmeter
authors.forename: Malin
authors.initials: M
authors.lastname: Grape
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D005787:Gene Frequency; D005838:Genotype; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D032023:Integrons / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D013548:Sweden / Q000453:epidemiology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014295:Trimethoprim / Q000494:pharmacology* / Q000627:therapeutic use; D014296:Trimethoprim Resistance / Q000235:genetics*; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000892:Anti-Infective Agents, Urinary; D001426:Bacterial Proteins; D007527:Isoenzymes; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase