Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli.
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.
Schilling
Joel D
JD
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lorenz
Robin G
RG
Hultgren
Scott J
SJ
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
D000892:Anti-Infective Agents, Urinary; D015662:Trimethoprim, Sulfamethoxazole Drug Combination