title: Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schilling
authors.forename: Robin G
authors.initials: RG
authors.lastname: Lorenz
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
mesh_terms: D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000627:therapeutic use*; D001437:Bacteriuria / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D012008:Recurrence; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000382:microbiology; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000892:Anti-Infective Agents, Urinary; D015662:Trimethoprim, Sulfamethoxazole Drug Combination