Multi-Drug Resistant Urinary Tract Infections in Ambulatory Settings

描述（由申请人提供）：在过去的十年中，多重耐药肠杆菌科（如大肠杆菌、肺炎克雷伯菌）的显著增加已经被注意到。其中最常见的是广谱β -内酰胺酶产生肠杆菌科（ESBL-EB）。ESBL-EB感染与发病率、死亡率和成本增加密切相关。此外，治疗这些感染的方法很少，有时甚至没有。虽然历史上仅限于医疗保健环境，但ESBL-EB已越来越多地出现在社区中。ESBL-EB在非医疗机构的出现引起了极大的关注，因为肠杆菌科导致了社区中绝大多数的尿路感染（uti）。此外，尿路感染是最常见的门诊细菌感染，具有重要的临床和经济意义。由于对这些感染的流行病学了解不完全，解决社区发病ESBL-EB尿道感染的有效策略尚不清楚。此外，社区发病ESBL-EB感染对抗生素治疗决策和临床结果的影响仍然知之甚少。碳青霉烯类抗生素仍然是ESBL-EB感染的首选治疗方法。然而，在过去的几年里，产碳青霉烯酶的肺炎克雷伯菌（KPC-KP）明显增加。尽管这些碳青霉烯耐药生物比ESBL-EB少得多，但它们进一步使ESBL-EB的治疗复杂化。然而，KPC-KP uti的流行病学和影响尚未得到研究。本应用的主要目的是：1)确定ESBL-EB引起社区发性尿路感染的表型和基因型特征；2)探讨社区发病ESBL-EB型尿路感染的危险因素；3)建立并验证社区发病ESBL-EB型尿路感染的临床预测规则；4)确定社区发性ESBL-EB UTI的临床影响。这些目标的主要假设是ESBL-EB UTI与既往抗生素使用相关，以及ESBL-EB UTI与临床失败相关。该应用程序的次要目的是：1)确定引起社区发病uti的KPC-KP的表型和基因型特征；2)探讨社区发病KPC-KP UTI的危险因素；3)建立并验证社区发病KPC-KP UTI的临床预测规则；4)了解社区发病KPC-KP UTI的临床影响。这项研究将为指导制定限制这些生物进一步出现的策略提供关键信息。该研究还将为经验性抗菌治疗的最佳选择提供重要见解。最后，在一个已建立的研究网络中纳入来自不同门诊护理站点网络的受试者将显著加强本研究结果的普遍性。

DESCRIPTION (provided by applicant): Significant increases in multidrug-resistant Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae) have been noted over the past decade. The most common of these are the extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EB). ESBL-EB infections are strongly associated with increased morbidity, mortality, and cost. Furthermore, there are few, and sometimes no, therapeutic options available to treat these infections. While historically limited to healthcare settings, ESBL-EB has increasingly been found in the community. The emergence of ESBL-EB in non-healthcare settings is of great concern as Enterobacteriaceae cause the vast majority of urinary tract infections (UTIs) in the community. Furthermore, UTIs are the most common outpatient bacterial infection with significant clinical and economic implications. Effective strategies to address the emergence of community-onset ESBL-EB UTIs are unknown due to the incomplete understanding of the epidemiology of these infections. Furthermore, the impact of community-onset ESBL-EB infections on antibiotic treatment decisions and clinical outcomes remains poorly understood. The carbapenem antibiotics remain the therapy of choice for ESBL-EB infections. However, in the past few years, K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) have increased significantly. While still much less common that ESBL-EB, these carbapenem-resistant organisms further complicate treatment of ESBL-EB. However, the epidemiology and impact of KPC-KP UTIs have not been studied. The primary aims of this application are: 1) To identify the phenotypic and genotypic characteristics of ESBL-EB causing community-onset UTIs; 2) To elucidate risk factors for community-onset ESBL-EB UTI; 3) To develop and validate a clinical prediction rule for community-onset ESBL-EB UTI; and 4) To identify the clinical impact of community-onset ESBL-EB UTI The primary hypotheses for these aims are that ESBL-EB UTI is associated with prior antibiotic use and that ESBL-EB UTIs are associated with clinical failure. The secondary aims of this application are: 1) To identify the phenotypic and genotypic characteristics of KPC-KP causing community-onset UTIs; 2) To elucidate risk factors for community-onset KPC-KP UTI; 3) To develop and validate a clinical prediction rule for community-onset KPC-KP UTI; and 4) To identify the clinical impact of community-onset KPC-KP UTI. This study will provide crucial information to guide development of strategies to limit further emergence of these organisms. The study will also offer important insights into optimal selection of empiric antimicrobial therapy. Finally, the inclusion of subjects from a diverse network of ambulatory care sites within an established research network will significantly strengthen the generalizability of the results of this study. PUBLIC HEALTH RELEVANCE: Community-onset urinary tract infections (UTIs) due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EB) have increased significantly in recent years. This study will investigate risk factors for ESBL-EB UTIs, develop and validate a clinical prediction rule for these infections, and identify the clinical impact of ESBL-EB UTIs. Results from this study will be vital for designing future interventions to limit further increases in ESBL-EB infections in ambulatory settings and optimize empiric antibiotic use for outpatient UTIs.