Chicago Community-Acquired Pneumonia Consortium

描述(申请人提供)：社区获得性肺炎和流感是美国第八大最常见的主要和重要的次要死亡原因。准确确定以人群为基础的发病率对于确定预防机会至关重要，例如扩大肺炎球菌结合疫苗中包括的血清型和可能在成人中使用。大量信息表明，自上次疾控中心赞助的基于人群的研究以来，CAP的病因和可能的频率发生了变化。不幸的是，甚至对哪些患者被纳入社区获得性肺炎的定义也进行了修订，没有对特定病原体的发病率进行适当的基于人群的分析。分子诊断技术的发展，如尿抗原检测和细菌和病毒基因的聚合酶链式反应(PCR)检测，不仅使病原学记录更加准确，而且将使更大比例的病例得以诊断。关于肺炎病原学的准确流行病学数据对经验性抗生素处方至关重要，但指南制定小组缺乏准确的最新数据。人们对使用降钙素原等生物标志物区分细菌和病毒感染的兴趣，是因为人们越来越担心与不适当的处方相关的耐药性和抗生素引发的并发症。所有这些因素结合在一起，需要一个基于人群的CAP发病率的当代估计基于高比例的病例准确的病因诊断。为了满足这一需求和疾控中心的筹资机会，我们建立了一个由芝加哥城市医院组成的联盟，以便在两年内每年招募1000名成年人和300名儿童。准确的基于人口的发病率估计需要纳入城市人口，包括各种种族/族裔和社会经济群体，以及在这些医院住院的患者所具有的获得医疗保健的不同机会。对社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)肺炎频率增加的担忧也表明，芝加哥是一个合适的研究地点，因为CA-MRSA皮肤定殖率很高。我们将使用基于邮政编码和公共数据库的创新地理分析来确定基于人口的发病率。微生物病原学将通过广泛的诊断测试来确定，包括常规的尿抗原检测、配对血清学和CDC批准的鼻咽拭子的一系列PCR分析。流感在细菌性肺炎中的作用，特别是肺炎球菌和CA-MRSA，将通过聚合酶链式反应、培养和配对血清学来积极探索。我们还将验证肺炎球菌基因的全血定量聚合酶链式反应，以提高诊断的敏感性和患者入院时的潜在风险分层。这一方案中广泛的诊断测试也提供了一个很好的机会来验证降钙素原--一种临床可用的生物标志物--区分病毒性肺炎和细菌性肺炎的能力。 与公共卫生相关：社区获得性肺炎经常合并流感或其他病毒感染，在美国仍然是一个重要的死亡原因。近年来，患者风险因素、抗生素耐药性以及导致肺炎的细菌和病毒都发生了变化。这项研究将明确定义城市人口肺炎的发病率，并通过增加新的分子诊断测试来确定导致这些肺炎的微生物。这些信息对于设计适当的未来预防和治疗计划至关重要。

DESCRIPTION (provided by applicant): Community-acquired pneumonia and influenza are the 8th most frequent primary and important secondary causes of death in the US. An accurate determination of the population-based incidence is critical to determine the opportunities for prevention, such as expansion of serotypes included in the conjugate pneumococcal vaccine and possible use in adults. A large body of information suggests that the etiology and possibly the frequency of CAP have changed since the last CDC-sponsored population-based study. Even the definition of which patients are included as community-acquired pneumonia has undergone revision, unfortunately without an appropriate population-based analysis of the pathogen-specific incidence. Developments in molecular diagnostic techniques, such as urinary antigen testing and polymerase chain reaction (PCR) detection of bacterial and viral genes, have not only made documentation of etiology more accurate but will allow diagnosis of a greater proportion of cases. Accurate epidemiologic data regarding etiology of pneumonia are critical for empirical antibiotic prescription but guideline development groups suffer from lack of accurate current data. Interest in the use of biomarkers, such as procalcitonin, to distinguish between bacterial and viral infections is being driven by increasing concern about resistance and antibiotic-induced complications associated with inappropriate prescriptions. All of these factors coalesce on the need for a contemporary population-based estimate of CAP incidence based on a high proportion of cases with accurate etiologic diagnosis. In response to this need and the resultant CDC Funding Opportunity, we have developed a consortium of urban Chicago hospitals, in order to recruit 1000 adults and 300 children per year for two years. An accurate population-based estimate of incidence requires inclusion of an urban population with the variety of racial/ethnic and socioeconomic groups and with the variable access to healthcare characterizing patients admitted to these hospitals. Concern regarding the increase in frequency of community-acquired methicillin- resistant S. aureus (CA-MRSA) pneumonia also suggests that Chicago is an appropriate site for study, based on the high rate of CA-MRSA skin colonization. We will use an innovative geographic analysis based on zip code and public databases to determine the population-based incidence. Microbial etiology will be determined by extensive diagnostic testing, including routine urinary antigen detection, paired serology, and a battery of CDC-approved PCR assays of nasopharyngeal swabs. The role of influenza in bacterial pneumonia, especially pneumococcal and CA-MRSA, will be aggressively explored with PCR, culture, and paired serology. We will also validate a whole blood quantitative PCR of a pneumococcal gene to increase the diagnostic sensitivity and for potential risk-stratification of patients at the time of admission. The extensive diagnostic testing in this protocol also offers an excellent opportunity to validate the ability of procalcitonin, a clinically available biomarker, to distinguish between viral and bacterial pneumonia. PUBLIC HEALTH RELEVANCE: Community-acquired pneumonia, often complicating influenza or other viral infections, remains an important cause of death in the US. Patient risk factors, antibiotic resistance, and the bacteria and viruses that cause pneumonia have changed in recent years. This study will clearly define the incidence of pneumonia in an urban population and determine the microorganisms causing these pneumonias by addition of new molecular diagnostic tests. This information is critical to design appropriate future prevention and treatment plans.