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

Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli
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DOI:
10.1128/iai.70.12.7042-7049.2002
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发表时间:
2002-12-01
影响因子:
3.1
通讯作者:
Hultgren, SJ
Hultgren, SJ
中科院分区:
医学2区
文献类型:
--
作者:
Schilling, JD;Lorenz, RG;Hultgren, SJ

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尿路感染(UTI)的一个更令人困惑的方面是它们的高复发倾向。有人提出,复发性感染是细菌从胃肠道(GIT)重新引入泌尿道(UT)的结果;然而,由于复发性UTI的重要子集是由相同的细菌菌株引起的,因此通过使用流行病学方法正式证明这一假设具有挑战性。我们在此提供的数据是通过使用UTI小鼠模型获得的,其中36%(5/14)的感染尿路致病性大肠杆菌(UPEC)的小鼠将至少有一次细菌性复发,21%(3/14)在急性UTI后6周内复发一次以上。经尿道感染的小鼠在其粪便和膀胱中形成UPEC储库。甲氧苄啶-磺胺甲恶唑(SXT)治疗10天可减少尿复发并根除粪便定植,而SXT治疗3天在28天的观察期内没有效果,尽管急性清除粪便定植。有趣的是,即使在10天的治疗方案后,SXT也无法根除膀胱储药器中的细菌,从而证明即使在长期抗生素治疗下,膀胱储药器也可以持续存在。
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.