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8大最常见的主要和重要的次要死亡原因。 准确确定基于人群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可能在成人中使用。 大量的信息表明，CAP的病因和可能的频率已经改变，因为最后一个CDC赞助的人群为基础的研究。 即使是社区获得性肺炎患者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检测，不仅使病因学的文件更加准确，而且将允许诊断更大比例的病例。 关于肺炎病原学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。 对使用生物标志物（如降钙素原）区分细菌和病毒感染的兴趣是由对与不适当处方相关的耐药性和抗生素诱导的并发症的日益关注所驱动的。 所有这些因素结合起来，需要一个当代人口为基础的估计CAP发病率的基础上，高比例的病例与准确的病因诊断。 为了满足这一需求和由此产生的CDC资助机会，我们已经建立了一个城市芝加哥医院联盟，以便每年招募1000名成人和300名儿童，为期两年。 准确的基于人群的发病率估计需要纳入城市人群，包括各种种族/民族和社会经济群体，以及在这些医院住院的患者获得医疗保健的可变特征。对社区获得性耐甲氧西林沙门氏菌频率增加的关注。金黄色葡萄球菌（CA-MRSA）肺炎的研究还表明，基于CA-MRSA皮肤定殖的高比率，芝加哥是研究的合适地点。 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群的发病率。 微生物病原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CDC批准的鼻咽拭子PCR检测。 流感在细菌性肺炎，特别是肺炎球菌和CA-MRSA中的作用，将通过PCR、培养和配对血清学进行积极探索。 我们还将验证肺炎球菌基因的全血定量PCR，以提高诊断灵敏度，并在入院时对患者进行潜在风险分层。 本方案中广泛的诊断测试也提供了一个极好的机会来验证降钙素原（一种临床可用的生物标志物）区分病毒性和细菌性肺炎的能力。 公共卫生相关性：社区获得性肺炎，通常并发流感或其他病毒感染，仍然是美国死亡的重要原因。 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肺炎在城市人群中的发病率，并通过增加新的分子诊断测试来确定引起这些肺炎的微生物。 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.