Molecular Characterisation of Trimethoprim Resistance in Escherichia coli and Klebsiella pneumoniae during a Two Year Intervention on Trimethoprim Use

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 phenotypicaly 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.