{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T04:25:32Z","timestamp":1769574332536,"version":"3.49.0"},"reference-count":30,"publisher":"BMJ","issue":"8","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2018,8,10]]},"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Methicillin-susceptible <jats:italic>Staphylococcus aureus<\/jats:italic> (MSSA) bacteraemia is a common and severe disease responsible for approximately 65\u2009000 deaths every year in Europe. Intravenous antistaphylococcal penicillins (ASP) such as cloxacillin are the current recommended antibiotics. However, increasing reports of toxicity and recurrent stock-outs of ASP prompted healthcare providers to seek for alternative antibiotic treatment. Based on retrospective studies, cefazolin, a first-generation cephalosporin, is recommended in patients at risk of severe ASP-associated toxicity.<\/jats:p>\n                  <jats:p>We hypothesised that cefazolin has a non-inferior efficacy in comparison to cloxacillin, with a better safety profile for the treatment of MSSA bacteraemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>The CloCeBa trial is an open-label, randomised, controlled, non-inferiority trial conducted in academic centres throughout France. Eligible patients are adults with MSSA bacteraemia without intravascular device or suspicion of central nervous system infection. Patients will be randomised (1:1) to receive either cloxacillin or cefazolin by the intravenous route, for the first 14 days of therapy. The evaluation criteria is a composite criteria of negative blood cultures at day 5, survival, absence of relapse and clinical success at day 90 after randomisation. Secondary evaluation criteria include both efficacy and safety assessments. Three ancillary studies are planned to describe the epidemiology of \u03b2-lactamase encoding genes, the ecological impact and pharmacokinetic\/pharmacodynamic parameters of cefazolin and cloxacillin. Including 300 patients will provide 80% power to demonstrate the non-inferiority of cefazolin over cloxacillin, assuming 85% success rate with cloxacillin and taking into account loss-to-follow-up, with a 0.12 non-inferiority margin and a one-sided type I error of 0.025.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>This protocol received authorisation from the ethics committee Sud-Est I on 13 November 2017 (2017-87-PP)and French National Agency for Medicines and Health Products (170661A-43). Results will be disseminated to the scientific community through congresses and publication in peer-reviewed journals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"NCT03248063\" ext-link-type=\"clintrialgov\">NCT03248063<\/jats:ext-link> and 2017-003967-36.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-023151","type":"journal-article","created":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T08:45:20Z","timestamp":1535791520000},"page":"e023151","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Efficacy of cloxacillin versus cefazolin for methicillin-susceptible <i>Staphylococcus aureus<\/i> bacteraemia (CloCeBa): study protocol for a randomised, controlled, non-inferiority trial"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct03248063","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03248063","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03419221","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-0794","authenticated-orcid":false,"given":"Charles","family":"Burdet","sequence":"first","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014D\u00e9partement d\u2019Epid\u00e9miologie, Biostatistiques et recherche Clinique, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Loubet","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014Service de maladies infectieuses, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Le Moing","sequence":"additional","affiliation":[{"name":"CHU de Montpellier, Montpellier, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Vindrios","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude Bernard\u2014Service de maladies infectieuses, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Esposito-Far\u00e8se","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude Bernard\u2014Unit\u00e9 de recherche Clinique, Assistance Publique\u2014Hopitaux de Paris, Paris, France"},{"name":"Inserm CIC 1425, Centre d\u2019Investigation Clinique, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgane","family":"Linard","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude Bernard\u2014D\u00e9partement d\u2019Epid\u00e9miologie, Biostatistiques et recherche Clinique, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"Ferry","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses, Hopital de la Croix-Rousse, Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Massias","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014Laboratoire de toxicologie, Assistance Publique\u2014Hopitaux de Paris, Paris, \u00cele-de-France, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Tattevin","sequence":"additional","affiliation":[{"name":"Service de Maladies Infectieuses et R\u00e9animation M\u00e9dicale, H\u00f4pital Pontchaillou, Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Wolff","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014Service de r\u00e9animation m\u00e9dicale et infectieuse, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Vandenesch","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rences des Staphylocoques, Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Grall","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat lLaude Bernard\u2014Laboratoire de bact\u00e9riologie, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Quintin","sequence":"additional","affiliation":[{"name":"H\u00f4pital Bichat Claude Bernard\u2014Unit\u00e9 de recherche Clinique, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"France","family":"Mentr\u00e9","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014D\u00e9partement d\u2019Epid\u00e9miologie, Biostatistiques et recherche Clinique, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Duval","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"Inserm CIC 1425, Centre d\u2019Investigation Clinique, AP-HP, H\u00f4pital Bichat-Claude Bernard, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois-Xavier","family":"Lescure","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137, INSERM, Universit\u00e9 Paris Diderot, Sorbonne Paris Cit\u00e9, INSERM, Paris, France"},{"name":"H\u00f4pital Bichat Claude Bernard\u2014Service de maladies infectieuses, Assistance Publique\u2014Hopitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2018,9,1]]},"reference":[{"key":"2025101813384047000_8.8.e023151.1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32833bcc8a"},{"key":"2025101813384047000_8.8.e023151.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6364"},{"key":"2025101813384047000_8.8.e023151.3","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.32"},{"key":"2025101813384047000_8.8.e023151.4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu301"},{"key":"2025101813384047000_8.8.e023151.5","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02032-13"},{"key":"2025101813384047000_8.8.e023151.6","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02800-14"},{"key":"2025101813384047000_8.8.e023151.7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cmi.2017.07.003","article-title":"Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review","volume":"24","author":"Loubet","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2025101813384047000_8.8.e023151.8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/phar.1892","article-title":"\u03b2-lactam therapy for methicillin-susceptible staphylococcus aureus bacteremia: a comparative review of cefazolin versus antistaphylococcal penicillins","volume":"37","author":"Li","year":"2017","journal-title":"Pharmacotherapy"},{"key":"2025101813384047000_8.8.e023151.9","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00243-16"},{"key":"2025101813384047000_8.8.e023151.10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/cid\/cix287","article-title":"Comparative effectiveness of cefazolin versus nafcillin or oxacillin for treatment of methicillin-susceptible staphylococcus aureus infections complicated by bacteremia: a nationwide cohort study","volume":"65","author":"McDanel","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2025101813384047000_8.8.e023151.11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03425.x"},{"key":"2025101813384047000_8.8.e023151.12","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00485-11"},{"key":"2025101813384047000_8.8.e023151.13","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04677-14"},{"key":"2025101813384047000_8.8.e023151.14","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-017-0148-z"},{"key":"2025101813384047000_8.8.e023151.15","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000296"},{"key":"2025101813384047000_8.8.e023151.16","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv319"},{"key":"2025101813384047000_8.8.e023151.17","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.jinf.2016.02.003","article-title":"The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia","volume":"72","author":"Tubiana","year":"2016","journal-title":"J Infect"},{"key":"2025101813384047000_8.8.e023151.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2005.03.004"},{"key":"2025101813384047000_8.8.e023151.19","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02487-07"},{"issue":"Suppl 2","key":"2025101813384047000_8.8.e023151.20","first-page":"S17","article-title":"Diagnosis and management of Staphylococcus aureus bacteraemia","volume":"35 Suppl 2","author":"Mitchell","year":"2005","journal-title":"Intern Med J"},{"key":"2025101813384047000_8.8.e023151.21","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl017"},{"key":"2025101813384047000_8.8.e023151.22","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq146"},{"key":"2025101813384047000_8.8.e023151.23","doi-asserted-by":"publisher","DOI":"10.1086\/599376"},{"key":"2025101813384047000_8.8.e023151.24","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.17.2066"},{"key":"2025101813384047000_8.8.e023151.25","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ495"},{"key":"2025101813384047000_8.8.e023151.26","unstructured":"National institutes of health, national cancer institute. Common Terminology Criteria for Adverse Events (CTCAE). 2010 Accessed on 07\/31\/2017 at https:\/\/evs.Nci.Nih.Gov\/ftp1\/ctcae\/ctcae_4.03_2010-06-14_quickreference_5x7.Pdf."},{"key":"2025101813384047000_8.8.e023151.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.03.010"},{"key":"2025101813384047000_8.8.e023151.28","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2007.3"},{"key":"2025101813384047000_8.8.e023151.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000087107"},{"key":"2025101813384047000_8.8.e023151.30","doi-asserted-by":"publisher","DOI":"10.1101\/gr.155465.113"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2018-023151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T20:38:47Z","timestamp":1760819927000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2018-023151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,9,1]]},"published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1136\/bmjopen-2018-023151"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2018-023151","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8]]}}}