{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:52:08Z","timestamp":1792572728871,"version":"4.5.0"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009930","name":"Basilea Pharmaceutica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009930","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Ceftobiprole is an advanced-generation cephalosporin with activity against methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic>, resistant pneumococci, and Enterobacterales. In a Phase 3 study in community-acquired bacterial pneumonia (CABP) performed prior to the current US Food and Drug Administration (FDA) guidance, clinical cure at the test-of-cure visit (TOC) was the primary endpoint. We present a re-analysis using early clinical success as the primary endpoint per the 2020 FDA CABP Guidance.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In this multicenter, double-blind study, patients with CABP requiring hospitalization were randomized to intravenous ceftobiprole (500\u2009mg q8h) or ceftriaxone (2000\u2009mg q24h) \u00b1 linezolid (600\u2009mg q12h) for 3\u201314 days. The primary endpoint was clinical success at Day 3 (improvement in \u22652 symptoms of chest pain, cough, productive sputum, difficulty breathing). A 12.5% non-inferiority margin was used.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Of the original 638 patients, 618 (97%) had\u2009\u2265\u20092 symptoms and were included in the Day 3 Intent-to-Treat (ITT) population for the re-analysis. The Day 3 modified ITT population consisted of 187 patients (29%) meeting additional FDA Guidance including Patient Outcomes Research Team (PORT) classification \u2265III. Ceftobiprole was non-inferior to ceftriaxone for clinical success for Day 3 ITT (71.0% vs 71.1%) and Day 3 modified ITT (71.1% vs 66.7%) populations. The 28-day all-cause mortality was 1.6% (ceftobiprole) vs 2.6% (ceftriaxone) in the Day 3 ITT population and 2.1% vs 7.8% in the Day 3 modified ITT population.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Ceftobiprole was non-inferior to ceftriaxone\u2009\u00b1\u2009linezolid for clinical success at Day 3 according to the current 2020 FDA CABP Guidance.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0326758","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T17:37:45Z","timestamp":1750786665000},"page":"e0326758","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ceftobiprole versus ceftriaxone \u00b1 linezolid in Community-Acquired Bacterial Pneumonia (CABP): Re-analysis of a randomized, phase 3 study using 2020 FDA guidance"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-8328","authenticated-orcid":true,"given":"Andrew F.","family":"Shorr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Friedmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ionescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Saulay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer I.","family":"Smart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-0212","authenticated-orcid":true,"given":"Marc","family":"Engelhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"4","key":"pone.0326758.ref001","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1007\/s12325-020-01248-7","article-title":"Burden of Community-Acquired Pneumonia and Unmet Clinical Needs","volume":"37","author":"J Ferreira-Coimbra","year":"2020","journal-title":"Adv Ther"},{"issue":"1","key":"pone.0326758.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41572-021-00259-0","article-title":"Pneumonia","volume":"7","author":"A Torres","year":"2021","journal-title":"Nat Rev Dis Primers"},{"issue":"5","key":"pone.0326758.ref003","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":"S Jain","year":"2015","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0326758.ref004","first-page":"494","article-title":"The incidence rate and economic burden of community-acquired pneumonia in a working-age population","volume":"6","author":"J Broulette","year":"2013","journal-title":"Am Health Drug Benefits"},{"issue":"7","key":"pone.0326758.ref005","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1128\/AAC.00029-07","article-title":"Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae","volume":"51","author":"TA Davies","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"issue":"38","key":"pone.0326758.ref006","doi-asserted-by":"crossref","first-page":"32096","DOI":"10.1074\/jbc.M112.355644","article-title":"Structural insights into the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of ceftobiprole","volume":"287","author":"AL Lovering","year":"2012","journal-title":"J Biol Chem"},{"issue":"10","key":"pone.0326758.ref007","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1128\/AAC.49.10.4210-4219.2005","article-title":"Antistaphylococcal activity of ceftobiprole, a new broad-spectrum cephalosporin","volume":"49","author":"T Bogdanovich","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"pone.0326758.ref008","unstructured":"Flamm RK, Sader HS, Streit JM, Jones RN. 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