Personalized Antibiotic Therapy in the Emergency Department: PANTHER Trial

项目摘要 尿路感染是急诊科最常见的感染之一。 在美国开抗生素是最常见的原因之一。不恰当的抗生素处方 治疗持续时间过长是抗菌素耐药性增加的两个主要原因。 急诊室出院患者的标准治疗是口服抗菌治疗，用于治疗 设置天数。医生建议患者完成全程的抗菌治疗。 无论症状缓解的时间长短。然而，这种方法忽略了寄主和病原因素。 会影响个体对治疗的独特反应。另一种方法是将患者引导到 在症状缓解后，即患者指导的抗菌药物持续时间(PDAD)后，停止使用抗生素。一个 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(AEs)和耐药性的风险 推广，而结果与用标准方法处理的结果相似。 随着耐氟喹诺酮类药物的流行，抗生素耐药性使UTI治疗复杂化 在美国的一些地方，大肠杆菌的比例现在超过了20%。美国传染病学会 指南发现了一个研究空白，无法理解第三代头孢菌素在门诊患者中的作用 在FQ耐药率较高的情况下治疗急性非复杂性肾炎(AUP)。需要 对于FQ来说，替代治疗尤其紧迫，因为越来越多的报告与FQ相关的严重 不良事件(SAE)。迫切需要确定可改进的替代抗菌策略 并降低不良反应和耐药性增加的风险。与短程FQ相反 对于β-内酰胺类药物的治疗，国际药品监督管理局建议疗程为10-14天，从而允许 探索PDAD的机会，以最大限度地减少附带的抗生素损害。 要克服与完成全程治疗的传统建议相关的惯性 并论证了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 口服第三代头孢菌素治疗PDAD与固定适应症特定持续时间的比较研究 患有AUP的妇女作为门诊患者接受治疗。如果我们的研究假设得到证实，那么来自一项大型临床研究的结果 试验将支持为AUP和其他疾病患者开出抗微生物治疗的方式的范式转变 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.