Rudick Charles N, Taylor Aisha K, Yaggie Ryan E, Schaeffer Anthony J, Klumpp David J
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America; Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
PLoS One. 2014 Nov 18;9(11):e109321. doi: 10.1371/journal.pone.0109321. eCollection 2014.
Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.
尿路感染(UTI)每年导致约800万人次门诊就诊,症状包括急性盆腔疼痛、排尿困难和刺激性排尿。由于尿路病原体对抗菌药物的耐药性不断增加,经验性使用抗菌药物治疗UTI变得复杂,但活生物治疗产品(LBP),如大肠杆菌的无症状菌尿(ASB)菌株,提供了规避抗菌药物耐药性的潜力。在此,我们在小鼠UTI模型中评估了作为LBP的ASB大肠杆菌相对于环丙沙星对感染和内脏疼痛的疗效。内脏疼痛通过用von Frey细丝进行机械刺激后盆腔区域的触觉异常性疼痛来量化。虽然环丙沙星促进了尿路致病性大肠杆菌(UPEC)的清除,但它并没有减轻盆腔触觉异常性疼痛,这是一种内脏疼痛的指标。相比之下,膀胱内或阴道内给予ASB大肠杆菌可使异常性疼痛得到类似膀胱内利多卡因的减轻。此外,ASB大肠杆菌对奇异变形杆菌、粪肠球菌和肺炎克雷伯菌引起的UTI异常性疼痛同样有效。因此,ASB大肠杆菌具有与当前护理标准相当的抗感染活性,同时还提供更好的镇痛效果。这些研究表明,ASB大肠杆菌是治疗UTI症状的新型LBP。