{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:58:04Z","timestamp":1790740684780,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Intensive studies have failed to identify an etiologic agent in &amp;gt;50% cases of community-acquired pneumonia (CAP). Bacterial pneumonia follows aspiration of recognized bacterial pathogens (RBPs) such as Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus after they have colonize the nasopharynx. We hypothesized that aspiration of normal respiratory flora (NRF) might also cause CAP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied 120 patients hospitalized for CAP who provided a high-quality sputum specimen at, or soon after admission, using Gram stain, quantitative sputum culture, bacterial speciation by matrix-assisted laser desorption ionization time-of-flight, and viral polymerase chain reaction. Thresholds for diagnosis of bacterial infection were \u2265105 colony-forming units (cfu)\/mL sputum for RBPs and \u2265106 cfu for NRF.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Recognized bacterial pathogens were found in 68 of 120 (56.7%) patients; 14 (20.1%) of these had a coinfecting respiratory virus. Normal respiratory flora were found in 31 (25.8%) patients; 10 (32.2%) had a coinfecting respiratory virus. Infection by \u22652 RBPs occurred in 10 cases and by NRF together with RBPs in 13 cases. Among NRF, organisms identified as Streptococcus mitis, which share many genetic features of S pneumoniae, predominated. A respiratory virus alone was found in 16 of 120 (13.3%) patients. Overall, an etiologic diagnosis was established in 95.8% of cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Normal respiratory flora, with or without viral coinfection, appear to have caused one quarter of cases of CAP and may have played a contributory role in an additional 10.8% of cases caused by RBPs. An etiology for CAP was identified in &amp;gt;95% of patients who provided a high-quality sputum at, or soon after, the time of admission.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofaa307","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T18:45:50Z","timestamp":1600195550000},"source":"Crossref","is-referenced-by-count":40,"title":["Normal Respiratory Flora as a Cause of Community-Acquired Pneumonia"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-066X","authenticated-orcid":false,"given":"Daniel M","family":"Musher","sequence":"first","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirus J","family":"Jesudasen","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Massachusetts General Hospital, Boston Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W","family":"Barwatt","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel N","family":"Cohen","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Moss","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C","family":"Rodriguez-Barradas","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas, USA"},{"name":"Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2020110408210314500_CIT0001","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jinf.2013.03.003","article-title":"Can an etiologic agent be identified in adults who are hospitalized for community-acquired pneumonia: results of a one-year study","volume":"67","author":"Musher","year":"2013","journal-title":"J Infect"},{"key":"2020110408210314500_CIT0002","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1500245","article-title":"Community-acquired pneumonia requiring hospitalization among U.S. adults","volume":"373","author":"Jain","year":"2015","journal-title":"N Engl J Med"},{"key":"2020110408210314500_CIT0003","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.cmi.2018.02.004","article-title":"Aetiology of lower respiratory tract infection in adults in primary care: a prospective study in 11 European countries","volume":"24","author":"Ieven","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2020110408210314500_CIT0004","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/cid\/ciz090","article-title":"Efficacy and safety of intravenous-to-oral lefamulin, a pleuromutilin antibiotic, for the treatment of community-acquired bacterial pneumonia: the Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial","volume":"69","author":"File","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0005","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1086\/648678","article-title":"Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods","volume":"50","author":"Johansson","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0006","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1128\/JCM.01805-16","article-title":"Improved detection of respiratory pathogens by use of high-quality sputum with TaqMan array card technology","volume":"55","author":"Wolff","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2020110408210314500_CIT0007","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/cid\/civ1214","article-title":"Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia","volume":"62","author":"Gadsby","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0008","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1714562","article-title":"Aspiration pneumonia","volume":"380","author":"Mandell","year":"2019","journal-title":"N Engl J Med"},{"key":"2020110408210314500_CIT0009","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/00005792-197211000-00001","article-title":"Anaerobic pleuropulmonary infections","volume":"51","author":"Bartlett","year":"1972","journal-title":"Medicine (Baltimore)"},{"key":"2020110408210314500_CIT0010","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1056\/NEJMra1312885","article-title":"Community-acquired pneumonia","volume":"371","author":"Musher","year":"2014","journal-title":"N Engl J Med"},{"key":"2020110408210314500_CIT0011","first-page":"339","article-title":"Microscopic and baceriologic analysis of expectorated sputum","volume":"50","author":"Murray","year":"1975","journal-title":"Mayo Clin Proc"},{"key":"2020110408210314500_CIT0012","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1001\/jama.1975.03260080056024","article-title":"The diagnostic value of sputum culture in acute pneumonia","volume":"233","author":"Thorsteinsson","year":"1975","journal-title":"JAMA"},{"key":"2020110408210314500_CIT0013","doi-asserted-by":"crossref","first-page":"444","DOI":"10.7326\/0003-4819-99-4-444","article-title":"Pneumonia and acute febrile tracheobronchitis due to Haemophilus influenzae","volume":"99","author":"Musher","year":"1983","journal-title":"Ann Intern Med"},{"key":"2020110408210314500_CIT0014","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/infdis\/134.5.428","article-title":"Bacteriology of the lower respiratory tract as determined by fiber-optic bronchoscopy and transtracheal aspiration","volume":"134","author":"Jordan","year":"1976","journal-title":"J Infect Dis"},{"key":"2020110408210314500_CIT0015","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1056\/NEJMoa1408544","article-title":"Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults","volume":"372","author":"Bonten","year":"2015","journal-title":"N Engl J Med"},{"key":"2020110408210314500_CIT0016","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1086\/657313","article-title":"Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in patients with community-acquired pneumonia","volume":"51","author":"File","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0017","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1086\/421497","article-title":"Diagnostic value of microscopic examination of Gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia","volume":"39","author":"Musher","year":"2004","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0018","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/1471-2334-14-534","article-title":"Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study","volume":"14","author":"Fukuyama","year":"2014","journal-title":"BMC Infect Dis"},{"key":"2020110408210314500_CIT0019","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1128\/JCM.26.5.846-849.1988","article-title":"Sputum gram stain assessment in community-acquired bacteremic pneumonia","volume":"26","author":"Gleckman","year":"1988","journal-title":"J Clin Microbiol"},{"key":"2020110408210314500_CIT0020","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10096-005-1316-8","article-title":"Value of intensive diagnostic microbiological investigation in low- and high-risk patients with community-acquired pneumonia","volume":"24","author":"van der Eerden","year":"2005","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2020110408210314500_CIT0021","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/cid\/ciz876","article-title":"Sputum Gram stain for bacterial pathogen diagnosis in community-acquired pneumonia: a systematic review and Bayesian meta-analysis of diagnostic accuracy and yield","volume":"71","author":"Ogawa","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2020110408210314500_CIT0022","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/infdis\/jit190","article-title":"Bacterial complications of respiratory tract viral illness: a comprehensive evaluation","volume":"208","author":"Falsey","year":"2013","journal-title":"J Infect Dis"},{"key":"2020110408210314500_CIT0023","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1001\/archinte.1974.00320150127017","article-title":"Transtracheal aspiration in pulmonary infection","volume":"133","author":"Ries","year":"1974","journal-title":"Arch Intern Med"},{"key":"2020110408210314500_CIT0024","first-page":"777","article-title":"Diagnostic accuracy of transtracheal aspiration bacteriologic studies","volume":"115","author":"Bartlett","year":"1977","journal-title":"Am Rev Respir Dis"},{"key":"2020110408210314500_CIT0025","doi-asserted-by":"crossref","first-page":"762","DOI":"10.3201\/eid2005.130953","article-title":"Streptococcus mitis strains causing severe clinical disease in cancer patients","volume":"20","author":"Shelburne","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"2020110408210314500_CIT0026","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1128\/JCM.01270-14","article-title":"Rothia bacteremia: a 10-year experience at Mayo Clinic, Rochester, Minnesota","volume":"52","author":"Ramanan","year":"2014","journal-title":"J Clin Microbiol"},{"key":"2020110408210314500_CIT0027","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s41479-018-0054-5","article-title":"Corynebacteria as a cause of pulmonary infection: a case series and literature review","volume":"10","author":"Yang","year":"2018","journal-title":"Pneumonia (Nathan)"},{"key":"2020110408210314500_CIT0028","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1186\/s12879-015-1004-y","article-title":"Pneumonia among adults hospitalized with laboratory-confirmed seasonal influenza virus infection-United States, 2005\u20132008","volume":"15","author":"Garg","year":"2015","journal-title":"BMC Infect Dis"},{"key":"2020110408210314500_CIT0029","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1378\/chest.127.6.2231","article-title":"Clinical significance of the infection-free interval in the management of acute bacterial exacerbations of chronic bronchitis","volume":"127","author":"Chodosh","year":"2005","journal-title":"Chest"},{"key":"2020110408210314500_CIT0030","first-page":"154","article-title":"Acute bacterial exacerbations in bronchitis and asthma","volume":"82","author":"Chodosh","year":"1987","journal-title":"Am J Med"},{"key":"2020110408210314500_CIT0031","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1099\/ijsem.0.001433","article-title":"Re-evaluation of the taxonomy of the Mitis group of the genus Streptococcus based on whole genome phylogenetic analyses, and proposed reclassification of Streptococcus dentisani as Streptococcus oralis subsp. dentisani comb. nov., Streptococcus tigurinus as Streptococcus oralis subsp. tigurinus comb. nov., and Streptococcus oligofermentans as a later synonym of Streptococcus cristatus","volume":"66","author":"Jensen","year":"2016","journal-title":"Int J Syst Evol Microbiol"},{"key":"2020110408210314500_CIT0032","doi-asserted-by":"crossref","first-page":"17959","DOI":"10.1038\/s41598-018-35921-3","article-title":"Streptococcus mitis expressing pneumococcal serotype 1 capsule","volume":"8","author":"Lessa","year":"2018","journal-title":"Sci Rep"},{"key":"2020110408210314500_CIT0033","doi-asserted-by":"crossref","first-page":"e01490","DOI":"10.1128\/mBio.01490-14","article-title":"Parallel evolution of Streptococcus pneumoniae and Streptococcus mitis to pathogenic and mutualistic lifestyles","volume":"5","author":"Kilian","year":"2014","journal-title":"mBio"},{"key":"2020110408210314500_CIT0034","doi-asserted-by":"crossref","first-page":"16416","DOI":"10.1073\/pnas.1111179108","article-title":"Autopsy series of 68 cases dying before and during the 1918 influenza pandemic peak","volume":"108","author":"Sheng","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020110408210314500_CIT0035","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1001\/jama.1934.02750480019005","article-title":"The significance of mixed infections in pneumococci pneumonia","volume":"103","author":"Finland","year":"1934","journal-title":"JAMA"},{"key":"2020110408210314500_CIT0036","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s10096-019-03526-x","article-title":"Comparison of Unyvero P55 pneumonia cartridge, in-house PCR and culture for the identification of respiratory pathogens and antibiotic resistance in bronchoalveolar lavage fluids in the critical care setting","volume":"38","author":"Gadsby","year":"2019","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2020110408210314500_CIT0037","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America","volume":"200","author":"Metlay","year":"2019","journal-title":"Am J Resp Crit Care Med"},{"key":"2020110408210314500_CIT0038","doi-asserted-by":"crossref","first-page":"e1004923","DOI":"10.1371\/journal.ppat.1004923","article-title":"The lung microbiome: new principles for respiratory bacteriology in health and disease","volume":"11","author":"Dickson","year":"2015","journal-title":"PLoS Pathog"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ofid\/article-pdf\/7\/9\/ofaa307\/34128913\/ofaa307.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ofid\/article-pdf\/7\/9\/ofaa307\/34128913\/ofaa307.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T13:21:15Z","timestamp":1604496075000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofaa307\/5906040"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofaa307","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9,1]]},"published":{"date-parts":[[2020,9,1]]},"article-number":"ofaa307"}}