Personalized Antibiotic Therapy in the Emergency Department: PANTHER Trial

项目摘要 尿路感染（UTIs）是急诊科（艾德）最常见的感染之一 在美国，抗生素处方最常见的原因之一是抗生素处方不当 和过长的治疗持续时间是增加抗微生物剂耐药性的两个主要原因。 从艾德出院回家的患者的标准治疗是口服抗生素治疗， 设置天数。医生建议患者完成整个疗程的抗菌治疗 无论症状消退的时间如何。然而，这种方法忽视了宿主和病原体因素 影响个体对治疗的独特反应。另一种方法是指导患者 在症状消退后停用抗生素，即，患者导向抗菌药物持续时间（PDAD）。一 关键的证据差距是，以患者为中心的方法尚未在临床试验中进行评估，但可能 减少不必要的抗生素暴露，降低不良事件（AE）和耐药性的风险 促进，而导致类似的结果，那些用标准的方法处理。 抗生素耐药性使UTI治疗复杂化，氟喹诺酮（FQ）耐药的流行 大肠杆菌现在超过20%，在美国的一些地方。美国传染病学会 指南确定了一个研究空白，以了解第三代头孢菌素对门诊患者的作用 治疗FQ耐药率高的急性无并发症肾盂肾炎（AUP）。需要 对于FQ替代治疗是特别紧迫的，因为越来越多的报告， 不良事件（SAE）。迫切需要确定替代抗菌策略， 患者结局，并降低AE和耐药促进的风险。与短期FQ相比， 对于β-内酰胺治疗方案，IDSA建议治疗持续时间为10-14天， 有机会探索PDAD，以尽量减少附带的抗生素损伤。 为了克服与完成整个疗程的传统建议相关的惯性 并证明进行大型随机对照试验的安全性和可行性，我们提出了一个试点 比较PDAD与使用口服第三代头孢菌素的固定适应症特异性持续时间的研究， 接受门诊治疗的AUP妇女。如果我们的研究假设得到证实，那么来自大型临床研究的结果 这项试验将支持抗生素治疗AUP和其他 常见传染病。

Project Summary Urinary tract infections (UTIs) are one of the most common infections seen in the emergency department (ED) and one of the most common reasons antibiotics are prescribed in the U.S. Inappropriate antibiotic prescribing and excessively long durations of therapy are two major causes of increasing antimicrobial resistance. Standard treatment for patients discharged home from the ED is an oral course of antimicrobial therapy for a set number of days. Physicians recommend that patients complete the full-course of antimicrobial therapy regardless of the time of symptom resolution. However, this approach disregards host and pathogen factors that affect an individual’s unique response to treatment. An alternative approach would be to direct a patient to discontinue their antibiotics upon symptom resolution, i.e., patient-directed antimicrobial duration (PDAD). A critical evidence gap is that a patient-centered approach has not been evaluated in clinical trials, but may decrease unnecessary antibiotic exposure, lowering the risk of adverse events (AEs) and resistance promotion, while resulting in similar outcomes as those treated with a standard approach. Antimicrobial resistance has complicated UTI treatment with the prevalence of fluoroquinolone (FQ)-resistant Escherichia coli now exceeding 20% in some US locations. The Infectious Diseases Society of America guidelines identified a research gap to understand the role of 3rd generation cephalosporins for outpatient treatment of acute uncomplicated pyelonephritis (AUP) in the setting of high rates of FQ resistance. The need for FQ alternative treatments is particularly pressing because of increasing reports of FQ-associated serious adverse events (SAEs). A critical need exists to identify alternative antimicrobial strategies that could improve patient outcomes and decrease the risk of AEs and resistance promotion. As opposed to short-course FQ treatment, for β-lactam regimens, IDSA recommends a 10-14 day treatment duration, thus allowing an opportunity to explore PDAD to minimize collateral antibiotic damage. To overcome the inertia associated with the traditional recommendation to complete a full-course treatment and demonstrate the safety and feasibility of conducting a large randomized controlled trial, we propose a pilot study comparing PDAD to a fixed indication-specific duration using an oral 3rd generation cephalosporin for women with AUP treated as outpatients. If our study hypothesis is confirmed, then results from a large clinical trial will support a paradigm shift in the way antimicrobial therapy is prescribed for patients with AUP and other common infectious diseases.