Improving empiric therapy in ambulatory care

描述（由申请人提供）：尿路感染（UTI）是在初级保健诊所治疗的最常见的细菌感染。在这些国家治疗的UTI的治疗选择 背景是经验性的，通常基于临床体征和症状、病史、尿液分析和抗菌素耐药性流行率的人群水平数据。尽管一线抗生素的可用性和适当性，但在过去十年中，更广谱的二线药物（如氟喹诺酮类）的使用显著增加。这导致了抗生素耐药性的增加，使得这些药物对其他严重感染的治疗选择不太可行。本申请的总体目标是制定一个风险评分，以指导在初级保健环境中接受治疗的女性对无并发症UTI的抗生素治疗进行谨慎的经验性选择。我们的中心假设是，特定的患者特征和病史可用于识别由于甲氧苄啶/磺胺甲恶唑（TMP/SMX）耐药肠杆菌科感染的高风险UTI患者。因此，本项目的基本原理是，通过识别最有可能发生TMP/SMX耐药感染的患者，使用氟喹诺酮类药物对UTI进行经验性治疗可以更好地针对这一高风险人群。我们计划通过追求两个具体目标来测试我们的中心假设并实现本申请的目标：（1）开发并验证风险评分，通过识别因TMP/SMX耐药肠杆菌科感染风险较高的患者，为无并发症UTI的成年女性患者提供经验性抗生素处方信息，以及（2）通过前瞻性评估患者安全性和科学有效性，确定在初级保健诊所使用风险评分作为决策辅助工具的可行性。预期结果是一个经验证的风险评分，用于识别因TMP/SMX耐药肠杆菌科感染风险高的UTI患者，可以通过更大规模的前瞻性研究在初级保健环境中安全地测试其有效性。从长远来看，这种工具预计将通过减少驱动多重耐药生物体出现的进化选择压力，对抗生素耐药细菌的生态学产生积极影响。这一点很重要，因为谨慎和适当的抗生素使用对于保留现有抗生素作为可行的治疗选择至关重要。

DESCRIPTION (provided by applicant): Urinary tract infections (UTIs) are the most common bacterial infection treated in primary care clinics. Selection of therapy for UTIs treated in these settings is empiric and typically based on clinical signs and symptoms, medical history, urinalysis, and population-level data of the prevalence of antimicrobial resistance. Despite availability and appropriateness of first-line antibiotics, use of broader spectrum, second-line agents such as fluoroquinolones have increased significantly over the last decade. This has contributed to increased antimicrobial resistance, making these agents less viable treatment options for other serious infections. The overall objective of this application, which represents the next step toward our long-term goal, is to develop a risk score for guiding prudent empiric selection of antibiotic therapy for uncomplicated UTI in women treated in primary care settings. Our central hypothesis is that specific patient characteristics and medical history can be used to identify UTI patients at high risk for infection due to trimethoprim/sulfamethoxazole (TMP/SMX)- resistant Enterobacteriaceae. Therefore, the rationale for this project is that empiric treatment o UTIs with fluoroquinolones can be better directed towards this high risk population by identifying patients most likely to have TMP/SMX-resistant infection. We plan to test our central hypothesis and accomplish the objective of this application by pursuing two specific aims: (1) Develop and validate a risk score to inform empiric antibiotic prescribing in adult female patients with uncomplicated UTI by identifying those at higher risk of infection due to TMP/SMX-resistant Enterobacteriaceae and (2) Establish the feasibility of using the risk score as a decision aid in primary care clinics by prospectively evaluating patient safety and scientific validity. The expected outcome is a validated risk score for identifying UTI patients at high risk of infection due to TMP/SMX-resistant Enterobacteriaceae that can be safely tested for effectiveness in primary care settings through a larger scale prospective study. Long-term, such a tool is expected to have a positive impact on the ecology of antibiotic- resistant bacteria by decreasing the evolutionary selective pressures driving the emergence of multi-drug resistant organisms. This is significant because prudent and appropriate antibiotic use is critical to preserving existing antibiotics as viable treatment options.