{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:01Z","timestamp":1787017021494,"version":"build-2736575974"},"reference-count":26,"publisher":"BMJ","issue":"3","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,12,18]]},"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Despite the availability of new antibiotics such as daptomycin, methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10\u2005mg\/kg\/24\u2005h intravenous; or group 2: daptomycin 10\u2005mg\/kg\/24\u2005h intravenous plus fosfomycin 2\u2005gr\/6\u2005g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72\u2005h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (\u03b1:0.05, \u00df: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12\u2005months of the completion of the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT01898338.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2014-006723","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T21:52:49Z","timestamp":1426110769000},"page":"e006723","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial"],"prefix":"10.1136","volume":"5","author":[{"given":"E","family":"Shaw","sequence":"first","affiliation":[{"name":"Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, Barcelona, 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P0088. 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) Barcelona, Spain 10\u201313 May 2014."},{"key":"2025101811432657000_5.3.e006723.21","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1471-2334-11-152","article-title":"High-dose daptomycin and fosfomycin treatment of a patient with endocarditis caused by daptomycin non susceptible Staphylococcus aureus: case report","volume":"26","author":"Chen","year":"2011","journal-title":"BMC Infect Dis"},{"key":"2025101811432657000_5.3.e006723.22","doi-asserted-by":"publisher","DOI":"10.1086\/524667"},{"key":"2025101811432657000_5.3.e006723.23","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir935"},{"key":"2025101811432657000_5.3.e006723.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.10.029"},{"key":"2025101811432657000_5.3.e006723.25","unstructured":"Daptomycin. 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