{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:38:14Z","timestamp":1792550294373,"version":"4.5.0"},"reference-count":15,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMW","doi-asserted-by":"publisher","award":["171002302"],"award-info":[{"award-number":["171002302"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014470","name":"Netherlands Heart Institute","doi-asserted-by":"publisher","award":["2009B095"],"award-info":[{"award-number":["2009B095"]}],"id":[{"id":"10.13039\/501100014470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["634809"],"award-info":[{"award-number":["634809"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008894","name":"Stryker","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Infections complicate the acute phase of stroke in one third of patients and especially pneumonia is associated with increased risk of death or dependency. In randomized trials of stroke patients, preventive antibiotics reduced overall infections, but did not reduce pneumonia or improve outcome. This may be explained by broad selection criteria, including many patients with a low risk of pneumonia. To assess the potential of selection of patients at high risk of pneumonia, we performed a post-hoc analysis in the Preventive Antibiotics in Stroke Study (PASS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>PASS was a multicentre phase 3 trial in acute stroke patients who were randomized to preventive ceftriaxone for four days within 24 hours or standard care. For this analysis patients were divided based on the ISAN risk score for pneumonia as follows: low (0\u20136), medium (7\u201314) and high (15\u201321). Primary outcomes were pneumonia rate during admission as judged by the treating physician, and by an independent committee; secondary outcomes were overall infections and unfavorable outcome (modified Rankin Scale \u22653). We adjusted with multivariable regression for possible confounders: age, stroke subtype and severity, pre-stroke dependency and diabetes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Pneumonia occurred more frequently in higher risk groups (25.7% (high), 9.0% (medium) 1.5%, (low)). The absolute difference in pneumonia rate between patients treated with ceftriaxone or standard care increased with the ISAN score (low: 0.5%, medium: 1.2%, high: 10.1%). After adjustment ceftriaxone reduced overall infections in the low and medium groups, not in the high-risk group. There was a trend towards reduction of pneumonia as judged by the committee (3.7% vs 13.6%, aOR = 0.164, p = 0.063) in the high-risk group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This post-hoc analysis of PASS confirmed higher rates of pneumonia with higher ISAN scores, and suggests that in acute stroke patients with an ISAN score of \u226515, preventive ceftriaxone for four days may reduce pneumonia rate.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0279700","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T18:54:59Z","timestamp":1672426499000},"page":"e0279700","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Preventive ceftriaxone in patients at high risk of stroke-associated pneumonia. A post-hoc analysis of the PASS trial"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3057-2010","authenticated-orcid":true,"given":"Wouter M.","family":"Sluis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willeke F.","family":"Westendorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik","family":"van de Beek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Nederkoorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Bart","family":"van der Worp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"pone.0279700.ref001","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1471-2377-11-110","article-title":"Post-stroke infection: a systematic review and meta-analysis","volume":"11","author":"WF Westendorp","year":"2011","journal-title":"BMC Neurol"},{"issue":"8","key":"pone.0279700.ref002","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1161\/STROKEAHA.106.478156","article-title":"Risk factors for chest infection in acute stroke: a prospective cohort study","volume":"38","author":"C Sellars","year":"2007","journal-title":"Stroke"},{"key":"pone.0279700.ref003","first-page":"CD008530","article-title":"Antibiotic therapy for preventing infections in patients with acute stroke","volume":"1","author":"WF Westendorp","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"pone.0279700.ref004","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1177\/2396987318772687","article-title":"PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke. Rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment","volume":"3","author":"H Reinink","year":"2018","journal-title":"Eur Stroke J"},{"issue":"1","key":"pone.0279700.ref005","doi-asserted-by":"crossref","first-page":"e001307","DOI":"10.1161\/JAHA.114.001307","article-title":"Can a novel clinical risk score improve pneumonia prediction in acute stroke care? A UK multicenter cohort study","volume":"4","author":"CJ Smith","year":"2015","journal-title":"J Am Heart Assoc"},{"issue":"9977","key":"pone.0279700.ref006","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/S0140-6736(14)62456-9","article-title":"The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial","volume":"385","author":"WF Westendorp","year":"2015","journal-title":"Lancet"},{"key":"pone.0279700.ref007","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","article-title":"CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting","volume":"36","author":"TC Horan","year":"2008","journal-title":"Am J Infect Control"},{"issue":"5","key":"pone.0279700.ref008","doi-asserted-by":"crossref","first-page":"e2158","DOI":"10.1371\/journal.pone.0002158","article-title":"Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial","volume":"3","author":"H Harms","year":"2008","journal-title":"PLoS One"},{"issue":"4","key":"pone.0279700.ref009","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1161\/STROKEAHA.107.499533","article-title":"Effects of prophylactic antibiotic therapy with mezlocillin plus sulbactam on the incidence and height of fever after severe acute ischemic stroke: the Mannheim infection in stroke study (MISS)","volume":"39","author":"S Schwarz","year":"2008","journal-title":"Stroke"},{"issue":"7","key":"pone.0279700.ref010","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1161\/01.STR.0000170644.15504.49","article-title":"The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial","volume":"36","author":"A Chamorro","year":"2005","journal-title":"Stroke"},{"issue":"10006","key":"pone.0279700.ref011","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/S0140-6736(15)00126-9","article-title":"Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial","volume":"386","author":"L Kalra","year":"2015","journal-title":"Lancet"},{"issue":"4","key":"pone.0279700.ref012","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/23969873211056445","article-title":"Preventive antibiotic therapy in acute stroke patients: A systematic review and meta-analysis of individual patient data of randomized controlled trials","volume":"6","author":"WF Westendorp","year":"2021","journal-title":"Eur Stroke J"},{"issue":"2","key":"pone.0279700.ref013","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1161\/STROKEAHA.118.022863","article-title":"Predicting Early Mortality of Acute Ischemic Stroke","volume":"50","author":"T Gattringer","year":"2019","journal-title":"Stroke"},{"issue":"1","key":"pone.0279700.ref014","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1161\/01.STR.0000047852.05842.3C","article-title":"Poor outcome after first-ever stroke: predictors for death, dependency, and recurrent stroke within the first year","volume":"34","author":"P Appelros","year":"2003","journal-title":"Stroke"},{"key":"pone.0279700.ref015","article-title":"Predictors of poor outcome despite successful endovascular treatment for ischemic stroke: results from the MR CLEAN Registry","author":"RA van de Graaf","year":"2021","journal-title":"J Neurointerv Surg"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T18:55:16Z","timestamp":1672426516000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0279700"}},"subtitle":[],"editor":[{"given":"Chinh Quoc","family":"Luong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,30]]},"references-count":15,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0279700","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,30]]}}}