Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections.
Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections.
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DOI：
10.1128/microbiolspec.uti-0013-2012
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发表时间：
2016-02
影响因子：
3.7
通讯作者：
Hultgren SJ
中科院分区：
文献类型：
--
作者：
O'Brien VP;Hannan TJ;Nielsen HV;Hultgren SJ
尿路感染（UTI）是人类最常见的细菌感染之一，每年影响数百万人。UTI在女性的整个生命周期中、在男婴中、在老年男性中、在具有潜在尿路异常的个体中以及在那些需要长期导尿的个体中（例如脊髓损伤患者或生活在疗养院中的无行为能力的个体）引起显著的发病率。严重的后遗症包括频繁复发、肾盂肾炎伴脓毒症、幼儿肾损害、早产和频繁使用抗生素的并发症，包括高水平抗生素耐药性和艰难梭菌结肠炎。肾盂肾炎大肠大肠杆菌（UPEC）引起绝大多数UTI，但不太常见的病原体如粪肠球菌和其他肠球菌经常利用异常或插入导管的尿路引起机会性感染。虽然抗生素治疗在历史上在控制UTI方面非常成功，但高复发率仍然是一个主要问题，并且许多个体患有慢性复发性UTI，需要长期预防性抗生素方案来预防复发性UTI。此外，在过去十年中，全球出现的多药耐药UPEC凸显了对替代治疗和预防策略的需求，以对抗UTI，包括抗感染药物疗法和疫苗。在这一章中，我们回顾了最近的进展，在该领域的尿路感染发病机制，重点是确定有前途的药物和疫苗的目标。然后，我们讨论了新的UTI药物和疫苗的开发，强调这些方法面临的挑战和需要更好地了解尿路粘膜免疫。
Urinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high-level antibiotic resistance and Clostridium difficile colitis. Uropathogenic E. coli (UPEC) cause the vast majority of UTI, but less common pathogens such as Enterococcus faecalis and other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity.