Accurate diagnosis of pneumococcal pneumonia in the acute-care setting remains a challenge due to the inadequate sensitivity of conventional diagnostic tests. Sputum cultures, which are likely to have the highest diagnostic yields of all specimen types, have been considered unreliable, due to their inability to differentiate colonization from infection. Our objective was to evaluate the potential clinical utility of a rapid quantitative real-time PCR assay using sputum samples for Streptococcus pneumoniae in adult patients with communityacquired pneumonia (CAP). A prospective clinical observational study of consecutively enrolled emergency department patients with CAP was performed; only those patients with excess good-quality sputum samples were included for evaluation. Sputum samples were tested for the presence of S. pneumoniae by using a quantitative PCR that targets the pneumolysin gene. PCR findings were compared with those of a composite reference standard comprising Gram staining of sputum samples and sputum/blood cultures. The area under the curve (AUC) and a log-transformed threshold, which provides the maximal sensitivity and specificity, were calculated. Of 487 subjects enrolled, 129 were evaluable. Receiver operating characteristic curve analysis demonstrated an AUC of 0.87. Sensitivity and specificity were 90.0 percent and 80.0 percent, respectively; positive and negative predictive values were 58.7 percent and 96.2 percent, respectively. We have demonstrated that a quantitative rapid pneumolysin PCR assay has favorable accuracy for diagnosis of pneumococcal pneumonia in adult patients with CAP; this assay may be a useful diagnostic adjunct for clinicians, particularly those practicing in the acute-care setting, where rapid pathogen identification may assist in selection of the most appropriate antibiotics.Streptococcus pneumoniae, the leading cause of communityacquired pneumonia (CAP), accounts for roughly two-thirds of cases in which an etiology can be found (11). Early and accurate diagnosis of pneumococcal pneumonia in the acute-care setting remains difficult due to the limitations of conventional diagnostic methods. Blood and sputum cultures are time-consuming and lack sensitivity (18, 30), particularly for patients with antecedent antibiotic exposure. Sputum culture is also difficult to interpret due to oropharyngeal contamination, and sputum Gram stains are frequently unreliable (2, 10, 17); pleural fluid aspirates are rarely performed. Newer pneumococcal urinary antigen tests offer the promise of improved sensitivity (70 to 82%) but are reported to have variable specificity based on the standards of comparison chosen, the manner in which the test is performed and interpreted, and the particular population studied (6,8,14,20,26). In the absence of a reliable, rapid diagnostic tool, empirical use of broad-spectrum antibiotics is recommended due to the uncertainties of identifying the causative pathogen (2). This approach to patient care results in significant and potentially unnecessary costs...