Reduction of Uneccessary Antibiotics in Adults by the Use of Viral Diagnostics

描述(申请人提供)：急性呼吸道感染是成人入院的最常见原因之一。在临床实践中，抗生素几乎是普遍使用的，因为往往不能做出特定的微生物诊断。最近使用敏感分子技术的证据表明，这些疾病中有很大一部分是由病毒引起的。虽然病毒感染可能导致继发性细菌感染，但对实际发病率的研究很少，而且可能被高估了。如果抗生素的使用只针对那些真正有细菌合并感染的患者，而不是只针对那些只有病毒感染的患者，那么通过减少与抗生素相关的并发症、抗菌素耐药细菌的传播和总体成本，整体患者护理将得到改善。在这项提案中，我们打算记录确诊为病毒感染的成人入院时的细菌率。我们假设，通过使用临床和实验室参数结合新的血清生物标记物，如降钙素原，可以确定有记录的病毒感染患者的细菌并发症风险较低。我们还相信，在大多数有病毒症记录的患者中，如果被认为细菌并发症的风险较低，医生将做出适当的反应，停用或停止使用抗生素。在第一至第二年，我们建议招募和仔细评估约1000名在2个冬季期间因呼吸道感染入院的成年人，以确定是否存在病毒和细菌感染，并使用标准和新的敏感分子技术进行评估。我们将定义一套准确预测病毒感染患者的临床和实验室变量，这些患者合并细菌感染的风险较低。在3-5年，我们将前瞻性地招募大约1500名相似的患者，并确定有记录的病毒呼吸道感染的患者，以及符合先前定义的预测细菌合并感染风险的标准的患者。在一项随机对照干预研究中，这些受试者将被随机分配到两个研究组中的一个。一半的患者将进入“干预”环节，医生将接受有关病毒感染和“低细菌风险状态”的信息，以及关于停用或停用抗生素的建议。另一半患者将接受“标准护理”，即抗生素的使用由主治医生自行决定，主治医生不会收到有关病毒诊断或细菌风险状况的额外信息。初步分析将确定与标准护理组相比，干预组患者的抗生素使用量是否显著减少。二次分析将检查干预组是否比标准护理组有更好的临床结果(住院时间更短，与抗生素相关的不良事件更少，发病率和死亡率相似或更低，因呼吸道疾病再次住院时间相似或更少)。公共卫生相关性该项目建议减少有记录的病毒性呼吸道感染住院患者不必要的抗生素使用。如果成功，对公众健康的主要影响将是限制抗菌素耐药性细菌的传播，并减少与抗生素使用相关的医疗费用和呼吸道感染治疗的并发症。

DESCRIPTION (provided by applicant): Acute respiratory tract infections are one of the most common reasons for hospital admission in adults. In clinical practice antibiotics are nearly universally administered because a specific microbial diagnosis is often not made. Recent evidence using sensitive molecular techniques indicate that a significant proportion of these illnesses are due to viruses. Although viral infection may predispose to secondary bacterial infections, the actual incidence has been poorly studied and is likely overestimated. If antibiotic use was targeted to only those patients with true bacterial co-infection and not to those with viral infection alone, overall patient care would be improved by reducing antibiotic related complications, spread of antimicrobial resistant bacteria, and overall costs. In this proposal we intend to document the rate of bacterial in adults admitted to the hospital with confirmed viral infection. We hypothesize that it is possible to identify patients with documented viral infections who are at low risk for bacterial complications by using clinical and laboratory parameters in combination with new serum biomarkers such as pro-calcitonin. We also believe that physicians will respond appropriately, by withholding or discontinuing antibiotics, in most patients with documented viral illnesses if considered to be at low risk for bacterial complications. In years1-2 we propose to recruit and carefully evaluate ~1000 adults admitted to the hospital with respiratory tract infections during 2 winters for the presence of viral and bacterial infection using standard and new sensitive molecular techniques. We will define a set of clinical and laboratory variables that accurately predict patients with viral infection who are at low risk for bacterial co-infection. In years 3-5, we will prospectively enroll a similar patient population of ~1500 subjects, and identify subjects with documented viral respiratory tract infections and who meet previously defined criteria predicting a low risk of bacterial co-infection. These subjects will be randomized to one of two study arms in a randomized controlled intervention study. Half will enter an "intervention" arm in which physicians receive information regarding the presence of a viral infection and "low bacterial risk status" along with a recommendation to withhold or discontinue antibiotics. The other half will receive "standard care" in which antibiotic use is administered at the discretion of the attending physician who will not receive additional information regarding viral diagnosis or bacterial risk status. The primary analysis will determine if there is a significant reduction in antibiotic use in patients in the intervention group compared to those in the standard care group. Secondary analysis will examine whether the intervention group has improved clinical outcomes (shorter hospitalization, less antibiotic related adverse events, similar or less morbidity and mortality, similar or fewer readmissions for respiratory illness) than the standard care group. PUBLIC HEALTH RELEVANCE This project proposes to decrease unnecessary antibiotic use in patients hospitalized with documented viral respiratory infections. If successful, the major effects on public health would be to limit the spread of antimicrobial resistant bacteria and to decrease health care costs associated antibiotic use and complications in the treatment of respiratory tract infections.