Abstract
BackgroundTrimethoprim 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 FindingsConsecutively 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/SignificanceThe 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.
Highlights
The increase in antibiotic resistance is a threat to global health [1]
We investigated the distribution of 13 dfr-genes and class I and II integrons in trimethoprim resistant E. coli and K. pneumoniae
The epidemiology of trimethoprim resistance in other species than E. coli has not been well studied at the molecular level
Summary
The increase in antibiotic resistance is a threat to global health [1]. Trimethoprim is commonly used in the treatment of urinary tract infections (UTI) in all parts of the world [2]. Already soon after the introduction of the drug, trimethoprim resistance was reported in several species [3] and are in unselected UTI materials at levels of 15–65% in E. coli [4,5,6]. This leads to treatment failure and increasing workload in primary healthcare and trimethoprim containing antibiotics are questioned as first line therapy [7]. Integrons are integrated in transposons predominantly located on plasmids and can insert, excise and express mobile gene cassettes, often antibiotic resistance genes [8]. 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
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