From January 1, 2010, to June 30, 2012, adults 18 years of age or older were enrolled at three hospitals in Chicago (John H. Stroger, Jr., Hospital of Cook County, Northwestern Memorial Hospital, and Rush University Medical Center) and at two in Nashville (University of Tennessee Health Science Center–Saint Thomas Health and Vanderbilt University Medical Center). We sought to enroll all eligible adults; therefore, trained staff screened adults for enrollment at least 18 hours per day, 7 days per week. Written informed consent was obtained from all the patients or their caregivers before enrollment. The study protocol was approved by the institutional review board at each participating institution and at the CDC. Weekly teleconferences, enrollment reports, data audits, and annual study-site visits were conducted to ensure uniform procedures among the study sites. Patients or their caregivers provided demographic and epidemiologic data, and medical charts were abstracted for clinical data. All the authors vouch for the accuracy and completeness of the data and analyses reported and for the fidelity of the study to the protocol. All the authors made the decision to submit the manuscript for publication.
Adults were eligible for enrollment if they were admitted to a study hospital on the basis of a clinical assessment by the treating clinician; resided in the study catchment area (see the Supplementary Appendix, available with the full text of this article at NEJM.org); had evidence of acute infection, defined as reported fever or chills, documented fever or hypothermia, leukocytosis or leukopenia, or new altered mental status; had evidence of an acute respiratory illness, defined as new cough or sputum production, chest pain, dyspnea, tachypnea, abnormal lung examination, or respiratory failure; and had evidence consistent with pneumonia as assessed by means of chest radiography by the clinical team within 48 hours before or after admission.
Patients were excluded if they had been hospitalized recently (<28 days for immunocompetent patients and <90 days for immunosuppressed patients), had been enrolled in the EPIC study within the previous 28 days, were functionally dependent nursing home residents,14 (link) or had a clear alternative diagnosis (see the Supplementary Appendix). Patients were also excluded if they had undergone tracheotomy, if they had a percutaneous endoscopic gastrostomy tube, if they had cystic fibrosis, if they had cancer with neutropenia, if they had received a solid-organ or hematopoietic stem-cell transplant within the previous 90 days, if they had active graft-versus-host disease or bronchiolitis obliterans, or if they had human immunodeficiency virus infection with a CD4 cell count of less than 200 per cubic millimeter.10 (link)