JAC Advance Access published online on November 8, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp387
Original research |
Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use
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1 Department of Medical Sciences, Section of Infectious Diseases, Uppsala University Hospital, Uppsala University, S-751 85 Uppsala, Sweden 2 Department of Clinical Microbiology, Central Hospital, S-351 85 Växjö, Sweden 3 Department of Mathematics, Stockholm University, S-106 91 Stockholm, Sweden 4 Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden 5 Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, S-751 23 Uppsala, Sweden 6 Department of Infectious Diseases, Central Hospital, S-351 85 Växjö, Sweden 7 Teleborg Health Center, S-351 85 Växjö, Sweden 8 Department of Pediatrics, Central Hospital, S-351 85 Växjö, Sweden 9 Swedish Strategic Program Against Antibiotic Resistance (Strama), S-171 82 Stockholm, Sweden 10 Department of Medical Sciences, Section of Clinical Bacteriology, Uppsala University Hospital, Uppsala University, Box 552, S-751 22 Uppsala, Sweden
Received 12 June 2009; returned 14 August 2009; revised 25 September 2009; accepted 1 October 2009
* Corresponding author. Department of Clinical Microbiology, Central Hospital, S-351 85 Växjö, Sweden. Tel: +46470-587478; Fax: +46470-587455; E-mail: martin.sundqvist{at}ltkronoberg.se
Objectives: The worldwide rapid increase in antibiotic-resistant bacteria has made efforts to prolong the lifespan of existing antibiotics very important. Antibiotic resistance often confers a fitness cost in the bacterium. Resistance may thus be reversible if antibiotic use is discontinued or reduced. To examine this concept, we performed a 24 month voluntary restriction on the use of trimethoprim-containing drugs in Kronoberg County, Sweden.
Methods: The intervention was performed on a 14 year baseline of monthly data on trimethoprim resistance and consumption. A three-parameter mathematical model was used to analyse the intervention effect. The prerequisites for reversion of resistance (i.e. fitness cost, associated resistance and clonal composition) were studied on subsets of consecutively collected Escherichia coli from urinary tract infections.
Results: The use of trimethoprim-containing drugs decreased by 85% during the intervention. A marginal but statistically significant effect on the increase in trimethoprim resistance was registered. There was no change in the clonal composition of E. coli and there was no measurable fitness cost associated with trimethoprim resistance in clinical isolates. The frequency of associated antibiotic resistances in trimethoprim-resistant isolates was high.
Conclusions: A lack of detectable fitness cost of trimethoprim resistance in vitro together with a strong co-selection of other antibiotics could explain the rather disappointing effect of the intervention. The result emphasizes the low possibility of reverting antibiotic resistance once established and the urgent need for the development of new antibacterial agents.
Key Words: intervention , Escherichia coli , population dynamic
Present address: Center for Disease Dynamics, Economics and Policy Resources for the Future, 1616 P Street NW, Washington, DC 20036, USA.
Present address: National Antimicrobial Resistance Monitoring System, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
The authors have contributed equally to the paper.