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Molecular techniques may improve\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      detection, but their clinical utility remains uncertain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective observational study, we compared conventional diagnostics with qPCR-based detection of\n                      <jats:italic>lytA<\/jats:italic>\n                      and\n                      <jats:italic>piaB<\/jats:italic>\n                      genes in nasopharyngeal, oropharyngeal, saliva, and sputum samples collected from adults with community-acquired pneumonia (CAP) and three control groups without acute respiratory symptoms. Stringent sample-specific cut-offs (\n                      <jats:sup>low<\/jats:sup>\n                      Cq), defined by the lowest cycle threshold (Cq) values observed among controls, were applied to reduce classification of background carriage as pneumococcal CAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      was detected by conventional methods in 53 (21.1%) of 251 CAP patients. Overall pneumococcal detection by qPCR was higher in CAP patients than in 564 individuals without CAP (35.9% vs. 10.3%, p &lt; 0.001), but pneumococcal density showed substantial overlap between CAP patients and controls and across aetiological groups within the CAP cohort. Using the\n                      <jats:sup>low<\/jats:sup>\n                      Cq criteria, 63 (25.1%) CAP patients met the study definition of pneumococcal CAP (PCAP), including ten (4.0%) identified by qPCR alone. Detection rates and pneumococcal density were highest in sputum and lower in patients pretreated with antibiotics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      qPCR targeting\n                      <jats:italic>lytA<\/jats:italic>\n                      and\n                      <jats:italic>piaB<\/jats:italic>\n                      increased pneumococcal detection in CAP patients, but substantial overlap in pneumococcal density limited its added diagnostic value for PCAP. Using stringent lowCq criteria, qPCR identified only a small number of additional PCAP cases beyond conventional diagnostics. Our findings do not support routine use of qPCR as a stand-alone diagnostic test for PCAP. Nevertheless, sputum-based molecular detection may contribute to future surveillance studies when combined with serotype-specific analyses.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10096-026-05655-6","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:15:09Z","timestamp":1788426909000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnosis of pneumococcal pneumonia using quantitative PCR targeting lytA and piaB in adult patients with community-acquired pneumonia"],"prefix":"10.1007","author":[{"given":"Nienke","family":"Paternotte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem R.","family":"Miellet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Nieuwenhuijsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Mariman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wil A.","family":"van der Reijden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Rozemeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth A.M.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Snijders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis H.","family":"van Werkhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.M.","family":"Bonten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Trzci\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G.","family":"Boersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"5655_CR1","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1001\/jama.2024.14796","volume":"332","author":"VM Vaughn","year":"2024","unstructured":"Vaughn VM, Dickson RP, Horowitz JK, Flanders SA (2024) Community-Acquired Pneumonia: A Review. 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All participants provided written informed consent.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"KT has received funds for unrestricted research grants from GlaxoSmithKline and Merck Sharp & Dohme, and consultation fees from Merck Sharp & Dohme, all paid directly to his home institution. All other authors report no potential conflict of interest.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}