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Infection and Immunity, December 2002, p. 7042-7049, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7042-7049.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effect of Trimethoprim-Sulfamethoxazole on Recurrent Bacteriuria and Bacterial Persistence in Mice Infected with Uropathogenic Escherichia coli

Joel D. Schilling,1 Robin G. Lorenz,2,3,{dagger} and Scott J. Hultgren1*

Department of Molecular Microbiology,1 Department of Pathology and Immunology,2 Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 631103

Received 24 April 2002/ Returned for modification 20 June 2002/ Accepted 28 August 2002

One of the more perplexing aspects of urinary tract infections (UTIs) is their high propensity to recur. It has been proposed that recurrent infections are a result of the reintroduction of bacteria from the gastrointestinal tract (GIT) to the urinary tract (UT); however, since a significant subset of recurrent UTIs are caused by an identical bacterial strain, it has been challenging to formally prove this hypothesis for same-strain recurrences by using epidemiologic approaches. We present data here obtained by using a mouse model of UTIs in which it was shown that 36% (5 of 14) of mice infected with uropathogenic Escherichia coli (UPEC) will have at least one bacteriuric recurrence, with 21% (3 of 14) having more than one recurrence during a 6-week period after an acute UTI. Intraurethrally infected mice develop UPEC reservoirs in both their feces and their bladders. Ten days of trimethoprim-sulfamethoxazole (SXT) therapy reduces urinary recurrences and eradicates fecal colonization, whereas 3 days of SXT treatment has no effect over a twenty-eight-day observation period despite clearing fecal colonization acutely. Interestingly, SXT is unable to eradicate bacteria from the bladder reservoir even after a 10-day treatment regimen, thus demonstrating that the bladder reservoir can persist even in the face of long-term antibiotic therapy.

* Corresponding author. Mailing address: Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-7059. Fax: (314) 362-3203. E-mail: hultgren{at}borcim.wustl.edu.

Editor: A. D. O'Brien

{dagger} Present address: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294.

Infection and Immunity, December 2002, p. 7042-7049, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.7042-7049.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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