Chicago Community-Acquired Pneumonia Consortium

描述（由申请人提供）：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，例如扩大结合肺炎球菌疫苗中包括的血清型以及在成人中使用的可能性。大量信息表明，自上次cdc发起的基于人群的研究以来，CAP的病因学和可能的频率已经发生了变化。甚至连哪些患者被纳入社区获得性肺炎的定义也经历了修订，不幸的是，没有对病原体特异性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反应（PCR）检测，不仅使病因记录更加准确，而且将使更大比例的病例得到诊断。关于肺炎病因的准确流行病学数据对于经验性抗生素处方至关重要，但指南制定小组缺乏准确的当前数据。由于越来越多的人担心耐药性和与不适当处方相关的抗生素引起的并发症，人们对使用生物标志物（如降钙素原）来区分细菌和病毒感染的兴趣日益浓厚。所有这些因素结合在一起，需要基于高比例的病例和准确的病因学诊断，以当代人群为基础的CAP发病率估计。为了满足这一需求以及由此产生的疾病预防控制中心资助机会，我们建立了芝加哥城市医院联盟，以便在两年内每年招募1000名成人和300名儿童。要对发病率进行准确的以人口为基础的估计，需要纳入不同种族/民族和社会经济群体的城市人口，并考虑到这些医院收治的病人获得医疗保健的机会各不相同。社区获得性耐甲氧西林金黄色葡萄球菌（CA-MRSA）肺炎发病率的增加也表明，芝加哥是一个合适的研究地点，因为CA-MRSA皮肤定植率很高。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以人口为基础的发病率。微生物病因学将通过广泛的诊断检测来确定，包括常规尿抗原检测、配对血清学和一系列经cdc批准的鼻咽拭子PCR检测。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PCR、培养和配对血清学积极探索。我们还将验证肺炎球菌基因的全血定量PCR，以提高患者入院时的诊断敏感性和潜在风险分层。该方案中广泛的诊断测试也为验证降钙素原（一种临床可用的生物标志物）区分病毒性和细菌性肺炎的能力提供了极好的机会。

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.