Efficacy of Antibiotics in Children with Acute Sinusitis: Which Subgroups Benefit?

抗生素对急性鼻窦炎儿童的疗效：哪些亚组受益？

• 批准号: 8926122
• 负责人: Nader Shaikh
• 金额: $ 102.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926122
• 关键词: 12 year old; Academy; Accounting; Acute; American; Amoxicillin; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacterial Infections; Child; Clavulanate; Clinical; Clinical Practice Guideline; Color; Controlled Clinical Trials; Data; Decision Making; Diagnosis; Diagnostic; Dose; Double-Blind Method; Electronics; Ensure; Fever; Goals; Guidelines; Haemophilus influenzae; Individual; Literature; Moraxella (Branhamella) catarrhalis; Nasopharynx; National Institute of Allergy and Infectious Disease; Nature; Nose; Outcome; Outcome Measure; Patients; Pediatrics; Placebo Control; Placebos; Population; Public Health; Randomized; Research; Respiratory System; Respiratory tract structure; Risk; Severities; Signs and Symptoms; Sinusitis; Streptococcus pneumoniae; Subgroup; Symptoms; Upper Respiratory Infections; Viral; Work; acute bacterial sinusitis; antimicrobial; base; clinical decision-making; diaries; evidence base; evidence based guidelines; experience; innovation; meetings; pathogen; placebo controlled study; public health relevance; respiratory; response

 DESCRIPTION (provided by applicant): Acute sinusitis is one of the most common diagnoses for which antimicrobials are prescribed for children in the US. Yet, available literature and our preliminary data suggest that only a subset of children diagnosed as having acute sinusitis based on current clinical criteria are likely to have bacterial disease. This finding, which is not entirely surprising, reflects the large overlap between symptoms and signs of an uncomplicated viral upper respiratory tract infection (URI) and acute bacterial sinusitis. Accordingly, in a population of children diagnosed as having acute sinusitis, response to antimicrobials is likely to be heterogeneous; those with true bacterial disease are likely to benefit substantially from antimicrobial therapy whereas those without bacterial disease would derive no benefit. The aim of this study is to identify subgroups of children who meet current diagnostic criteria for acute sinusitis, but in whom antimicrobial therapy provides no benefit. This objective will be achieved by conducting a large, randomized, double-blind, placebo-controlled clinical trial in children 2 to 12 years of age with persistent or worsening presentations of acute sinusitis. Children will be randomized to receive amoxicillin-clavulanate or placebo. Based on preliminary data we have gathered, we hypothesize that the subgroup of children who harbor no respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) in their nasopharynx, and the subgroup of children whose nasal discharge is grossly clear, are unlikely to have bacterial disease and therefore will not benefit from antimicrobial therapy. Innovations that will differentiate this study from previous studies include: 1) an experienced multidisciplinay research team working in a multicenter setting; 2) use of a well-validated measure of outcome; 3) use of electronic diaries to minimize the amount of missing data; and 4) a priori identification of subgroups likely to respond differently to antimicrobial therapy. Should the proposed hypotheses be borne out, clinicians would be provided a basis for restricting antimicrobial use to specific subgroups of children who are most likely to benefit from it. Reduction of unnecessary antimicrobial use constitutes an important contribution to both individual and public health and is in accord with our long-term goal and that of NIAID. Absent a study of this nature, it seems likely that many children with uncomplicated viral URI will continue to be treated inappropriately with antimicrobials. This trial will offer a departure from an "all-or-none" approach to decision-making regarding antimicrobials for acute sinusitis, and permit a more nuanced, evidence-based approach.

 描述（由申请人提供）：急性鼻窦炎是美国儿童最常见的诊断之一，因此处方了抗菌药物。然而，现有的文献和我们的初步数据表明，只有一个子集的儿童诊断为急性鼻窦炎的基础上，目前的临床标准可能有细菌性疾病。这一发现， 完全令人惊讶的是，这反映了简单的病毒性上呼吸道感染（URI）和急性细菌性鼻窦炎的症状和体征之间的大量重叠。因此，在被诊断为急性鼻窦炎的儿童人群中，对抗菌剂的反应很可能是 是异质的;那些患有真正细菌性疾病的人可能从抗菌治疗中获益，而那些没有细菌性疾病的人则不会获益。本研究的目的是确定符合当前急性鼻窦炎诊断标准，但抗菌治疗无效的儿童亚组。这一目标将通过在2至10岁儿童中进行一项大型、随机、双盲、安慰剂对照临床试验来实现。 12岁，急性鼻窦炎持续或恶化。儿童将随机接受阿莫西林-克拉维酸或安慰剂治疗。根据我们收集的初步数据，我们假设鼻咽部没有呼吸道病原体（肺炎链球菌、流感嗜血杆菌或卡他莫拉菌）的儿童亚组和鼻涕非常清澈的儿童亚组不太可能患有细菌性疾病，因此不会从抗菌治疗中获益。本研究与以往研究的不同之处包括：1）经验丰富的多学科研究团队在多中心环境中工作; 2）使用经过充分验证的结局指标; 3）使用电子日志以最大限度地减少缺失数据量; 4）先验识别 可能对抗菌治疗有不同反应的亚组。如果所提出的假设得到证实，临床医生将提供一个基础，限制抗菌药物的使用，以特定的亚组的儿童谁是最有可能受益于它。减少不必要的抗菌药物的使用构成了一个重要的贡献，个人和公共健康， 这雅阁我们长期目标和NIAID的长期目标。如果没有这种性质的研究， 许多无并发症病毒性URI的儿童将继续接受不适当的抗菌药物治疗。这一试验将提供一个偏离“全有或全无”的决策方法 关于急性鼻窦炎的抗菌药物，并允许一个更微妙的，以证据为基础的方法。