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Molecular Characterisation of Trimethoprim Resistance in Escherichia coli and Klebsiella pneumoniae during a 2 year intervention on Trimethoprim use
Dept. of Microbiology, Tumor and Cell Biology (MTC) Div. of Clinical Microbiology, Karolinska Institutet, Stockholm.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (Infektionssjukdomar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Dept. of Microbiology, Tumor and Cell Biology (MTC) Div. of Clinical Microbiology, Karolinska Institutet, Stockholm.
2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 2, e9233- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 5, no 2, e9233- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-112601DOI: 10.1371/journal.pone.0009233ISI: 000274590500015PubMedID: 20169085OAI: oai:DiVA.org:uu-112601DiVA: diva2:286937
Available from: 2010-01-15 Created: 2010-01-15 Last updated: 2010-12-29Bibliographically approved
In thesis
1. Antibiotic Resistance and Population Dynamics of Escherichia coli in Relation to a Large Scale Antibiotic Consumption Intervention
Open this publication in new window or tab >>Antibiotic Resistance and Population Dynamics of Escherichia coli in Relation to a Large Scale Antibiotic Consumption Intervention
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotic resistance challenges the practice and development of modern medicine. The aim of this thesis was to test the hypothesis that antibiotic resistance is reversible once the selection pressure of an antibiotic is removed. A decisive reduction (85%) in trimethoprim and trimethoprim-sulfamethoxazole over 24 months in Kronoberg County, Sweden, is described. The resistance baseline prior to the intervention and the effects of the intervention on resistance levels, trimethoprim resistance genes (dfr-genes) and population structure in Escherichia coli were studied.

The effects of different algorithms for excluding patient duplicate isolates were small but systematic. An identical algorithm was used throughout.

The drastic decrease in the use of trimethoprim containing drugs did not result in a corresponding decrease in trimethoprim resistance. This was true both for total trimethoprim resistance and for trimethoprim mono-resistance. The distributions of E. coli phenotypes, dfr-genes and E. coli sequence types were stable. The marginal effect on resistance rates was explained by a low fitness cost of trimethoprim resistance observed in vitro and the high levels of associated resistance in trimethoprim resistant isolates.

Trimethoprim resistance was, although widespread in the E. coli population, more common in certain E. coli sequence types. The distributions of dfr-genes were different in E. coli and K. pneumoniae and between different E. coli sequence types. These results indicate mechanisms related to the genetic back-bone of E coli to be important for the acquisition and persistence of antibiotic resistance.

The findings of this thesis indicates that, at least for some classes of antibiotics, we may have overestimated the usefulness of a strategy for reversing antimicrobial resistance based on the fitness cost of resistance. We have equally underestimated the conserving effects of associated resistance. The stability of the dfr-genes and E. coli sequence types underlines the importance of associated resistance and successful lineages in the spread and maintenance of antibiotic resistance in E. coli.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 512
Keyword
reversibility, trimethoprim, dfr, associated resistance, MLST
National Category
Infectious Medicine Microbiology in the medical area Microbiology in the medical area
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:uu:diva-112190 (URN)978-91-554-7700-4 (ISBN)
Public defence
2010-02-26, Universitetshuset, sal IV, Övre Slottsgatan, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2010-02-02 Created: 2010-01-11 Last updated: 2010-02-02Bibliographically approved

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