Antibiotic Use and Adverse Events

描述(由申请人提供)：美国人口中抗生素暴露的估计范围从每3年一次到几乎每年两次；几乎一半的美国门诊抗生素使用是不必要的。过度使用抗生素会造成个人和社会后果，包括不良药物事件(ADE)和不断增加的抗菌素耐药性。在患者与提供者接触的层面上限制过度使用的努力收效甚微。即使抗生素使用带来的相对较小的个体ADE风险也可能导致大量的人群归因风险。很少有关于抗生素ADE的研究包括没有抗生素暴露的对照组患者。虽然随机临床试验是确保暴露组和非暴露组之间的可比性的理想方法，但它们并不总是可行的。观察数据可以提供一种有效的方式来研究抗生素使用的个体后果，但研究需要解决混淆的问题，特别是适应症的混淆。因此，加强调整方法以确保治疗组和对照组之间的可比性将有助于我们最佳地利用观测数据。这项回溯性队列研究使用来自英国全科实践研究数据库的观察数据来研究抗生素使用导致的不良反应。这项研究利用了抗生素治疗急性呼吸道感染(ARIS)是可变的这一事实，反映了临床医生的信念、患者的偏好以及潜在的临床和非临床因素。主要目的是比较在ARI办公室就诊的条件下开抗生素的患者与未接触抗生素的ARI办公室就诊患者之间发生严重不良事件的风险。假设是，抗生素的使用与不良事件风险的增加有关；任何风险的增加都可以归因于ADE。第二个目的是比较暴露于不同类别抗生素的ARIS患者之间发生严重不良事件的风险，以及比较暴露于抗生素的ARIS患者与未暴露于抗生素的患者之间发生较轻不良事件的风险。探索控制患者共病情况、就诊次数等临床因素混杂的方法。这项研究将支持申请者发展成为一名富有成效的独立调查员。这项研究与公共卫生有关，因为它建议评估抗生素相关ADE的个体风险，并改进方法，以解决使用观测数据固有的混淆问题。结果将有助于计划一项使用电子病历数据的前瞻性研究，以更有效地将个人风险和好处纳入抗生素处方决策，将抗生素处方的不良结果降至最低，并减少不必要的抗生素使用。

DESCRIPTION (provided by applicant): Estimates of antibiotic exposure in the U.S. population range from once every 3 years to almost twice yearly; almost half of U.S. outpatient antibiotic use is unnecessary. Antibiotic overuse has individual and societal consequences, including adverse drug events (ADEs) and escalating antimicrobial resistance. Efforts to limit overuse at the patient-provider encounter level have had limited success. Even relatively small individual ADE risks from antibiotic use could result in large population attributable risks. Few studies on antibiotic ADEs have included a control group of patients without antibiotic exposure. While randomized clinical trials are ideal for ensuring comparability between exposed and unexposed groups, they are not always feasible. Observational data could offer an efficient way to study individual consequences of antibiotic use, but studies need to address confounding issues, especially confounding by indication. Enhanced adjustment methods to ensure comparability between treatment and control groups would thus help us make optimal use of observational data. This retrospective cohort study uses observational data from the UK's General Practice Research Database to study ADEs consequent to antibiotic use. This study takes advantage of the fact that antibiotic treatment for acute respiratory infections (ARIs) is variable, reflecting clinician beliefs, patient preferences and underlying clinical and nonclinical factors. The primary aim is to compare the risk of a severe adverse event between patients prescribed antibiotics, conditional on an office visit for an ARI vs. the risk for patients with ARI office visits not exposed to antibiotics. The hypothesis is that antibiotic use is associated with an increased risk of adverse events; any increased risk can be attributable to ADEs. Secondary aims are to compare the risk of a severe adverse event between patients with ARIs exposed to different classes of antibiotic drugs, and to compare the risk of a less-severe adverse event between patients with ARIs exposed to antibiotics vs. the risk for unexposed patients. We will explore methods to control for confounding by patient clinical factors such as comorbid conditions and visit frequency. This study will support the applicant's development into a productive independent investigator. This study is relevant to public health as it proposes to assess the individual risk of antibiotic-related ADEs and refine methodologies to address confounding issues inherent with using observational data. Results would help plan a prospective study using electronic medical record data to more effectively incorporate individual risks and benefits into antibiotic prescribing decisions, minimize adverse outcomes of antibiotic prescribing, and decrease unnecessary antibiotic use.