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？

基本信息

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
项目类别：
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

项目摘要

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开具抗菌药物的诊断之一，然而，现有文献和我们的初步数据表明，根据目前的情况，只有一小部分儿童被诊断为患有急性鼻窦炎。临床标准是很可能有细菌性疾病，而这一发现则不然。完全令人惊讶的是，这反映出单纯性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存在很大的重叠，因此，在被诊断患有急性鼻窦炎的儿童群体中，抗菌药物的反应可能会有所不同。具有异质性；那些患有真正的细菌性疾病的患者可能会从抗菌药物治疗中获益匪浅，而那些没有细菌性疾病的儿童则不会受益，本研究的目的是确定符合当前急性鼻窦炎诊断标准但接受抗菌药物治疗的儿童亚组。这一目标将通过在 2 至 2 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。患有持续或恶化的急性鼻窦炎的 12 岁儿童将被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，我们发现不携带呼吸道病原体（肺炎链球菌、嗜血杆菌）的儿童亚组。鼻咽部有流感杆菌或卡他莫拉菌），而鼻分泌物非常清澈的儿童亚群不太可能患有细菌性疾病，因此不会使本研究与之前的研究不同的创新之处包括：1）在多中心环境中工作的经验丰富的多学科研究团队；2）使用经过充分验证的结果测量；3）使用电子日记来最大限度地减少感染。缺失数据的数量；以及 4) 先验识别如果所提出的假设得到证实，毕肖普将获得将抗菌药物的使用限制在最有可能从中受益的特定儿童亚群的基础上，减少不必要的抗菌药物使用是一项重要的工作。对个人和公共健康的贡献根据我们的长期目标和 NIAID 的目标，如果没有这种性质的研究，这似乎是可能的。许多患有单纯性病毒性上呼吸道感染的儿童将继续接受不适当的抗菌药物治疗，这项试验将改变“全有或全无”的决策方法。关于急性鼻窦炎的抗菌药物，并允许采取更细致、基于证据的方法。