Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli - PubMed (original) (raw)

Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli

Joel D Schilling et al. Infect Immun. 2002 Dec.

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.

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Figures

FIG. 1.

Kinetic analysis of urine and feces after infection with UPEC. C57BL/6 mice were infected with UTI89 (M1 to M5) or UTI89 SR (M6 to M15), and bacterial titers in urine (▪) and feces (□) samples were determined every other day for 6 weeks (42 days). Five mice were together in each cage with M1 to M5 (cage 1), M6 to M10 (cage 2), and M11 to M15 (cage 3). M10 was not infected with UTI89 SR. ✽, No urine collected; ♦, no feces collected.

FIG. 2.

Bacterial persistence in the bladders of mice infected with UPEC. Bladders were removed from the indicated mice 6 weeks after intraurethral infection with UTI89 (M1 to M5) or UTI89 SR (M6 to M15), and the bacterial titers in the tissue were determined. K, Kidney scarring; B, persistent bacteriuria; U, uninfected.

FIG. 3.

Effect of SXT on bacteriuric recurrences and the fecal reservoir. C57BL/6 mice were infected intraurethrally with UTI89 SR and subsequently treated with SXT for 3 days (M31 to M35) or 10 days (M36 to M40), or left untreated (M26 to M30). Urine and fecal samples were collected at 6 h after infection and daily thereafter for 28 days, and then titers were determined for the CFU of UTI89 SR. Mouse key: M26, M31, and M36 (yellow bars); M27, M32, and M37 (blue bars); M28, M33, and M38 (red bars); M29, M34, and M39 (green bars); M30, M35, and M40 (black bars).

FIG. 4.

Effect of SXT on bacterial persistence in the bladder. C57BL/6 mice were infected with UTI89 SR and treated with SXT for 3 days (black circles) or 10 days (red circles) or were left untreated (white circles). Bladders were harvested at days 3 and 28 after infection, and serial dilutions of the bladder homogenates were titered to determine the level of culturable UTI89 SR remaining in the bladder. The black bars indicate the median values.

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Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli - PubMed (original) (raw)