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Pneumonia was defined as the presence of a new infiltrate on a chest radiograph plus fever (temperature ��38.0��C) and/or respiratory symptoms. Primary viral pneumonia was diagnosed in patients presenting pneumonia with negative respiratory and blood bacterial cultures and negative urine antigen tests. Bacterial co-infection was diagnosed in patients with one or more positive cultures obtained from blood, normally sterile fluids, or sputum and/or a positive urinary antigen test. Sputum Gram staining was performed on a purulent portion of each sample. Samples were considered to be of good quality when >25 polymorphonuclear cells and  a predominant bacterial morphotype by oil immersion [http://www.selleckchem.com/products/Cyclopamine.html Cyclopamine ic50] microscopy. To stratify patients according to risk, we used community-acquired pneumonia scores: pneumonia severity index (PSI) and CURB-65 (confusion, urea nitrogen, respiratory rate, blood pressure, 65?years of age and older) [16,17]. Underlying medical conditions were assessed according to the Charlson Comorbidity Index [18]. Other comorbidities such as immunosuppression, neuromuscular disorders and sickle-cell disease were also recorded. A vaccinated patient was any individual who had received a pneumococcal vaccine in the previous 5?years or [http://www.selleckchem.com/products/BI-2536.html selleck kinase inhibitor] a pandemic influenza A (H1N1) 2009 vaccine in the previous year. Obesity was defined as BMI?��?30. The diagnosis of septic shock was based on the definition of the [https://en.wikipedia.org/wiki/BML-190 BML-190] 1992 ACCP/SCCM Consensus Conference Committee [19]. Altered mental status was defined as disorientation with respect to person, place or time that was not known to be chronic, stupor or coma. Severe disease was defined as the composite outcome of ICU admission or death. The diagnosis of acute respiratory distress syndrome was established by the attending physicians, based on the usual practice guidelines [20]. Because hospital admission criteria were not standardized, we cannot rule out the possibility that factors other than disease severity may have contributed to site-of-care decisions. Therefore, to control for possible confounding because of differences in the criteria governing admission to hospital, we defined patients as having complicated pneumonia when any of the following were observed at presentation: intercostal retractions, tachypnoea (respiratory rate ��30?per min), Pao2/Fio2?