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Linezolid, though bacteriostatic, is effective in MRSA pneumonia and has excellent meningeal penetration. Therefore, the combination of both antibiotics can be required in some patients with disseminated MRSA infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to evaluate the in vitro activity of linezolid plus daptomycin against MRSA and glycopeptide-intermediate Staphylococcus aureus (GISA) strains and to determine the efficacy of linezolid monotherapy administered every 12 h versus every 8 h versus the combination of linezolid-q12h plus daptomycin against MRSA and GISA experimental endocarditis (EE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro time-kill studies were performed using standard (105 cfu\/L) and high (109 cfu\/mL) inoculum of six MRSA strains, including one GISA strain. MRSA-277 and GISA-700788 were selected for the EE model. Animals were treated with linezolid-q12h (600 mg\/kg\/12 h), linezolid-q8h (600 mg\/kg\/8 h), daptomycin (6 mg\/kg\/day) or daptomycin plus linezolid-q12h mimicking human-like serum levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Linezolid-q8h and linezolid-q12h showed similar activity in MRSA-277 EE (P\u200a=\u200a0.15). Against GISA-700788 endocarditis, linezolid-q8h was more effective than linezolid-q12h (P\u200a&amp;lt;\u200a0.001). Daptomycin monotherapy was very effective against MRSA-277 and GISA-700788 EE, sterilizing 70% and 60% of valvular vegetations, respectively. Daptomycin plus linezolid-q12h was similarly effective at 60% and 56%, respectively. This combination showed neither in vitro nor in vivo antagonism, and daptomycin-non-susceptible strains were not recovered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increasing linezolid to 600 mg\/8 h might be useful as initial treatment in clinical practice. If required, the combination of daptomycin plus linezolid-q12h could be a suitable option in MRSA\/GISA bacteraemia\/endocarditis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf149","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T07:46:40Z","timestamp":1746517600000},"page":"1933-1941","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of linezolid in monotherapy q12h versus q8h versus combined with daptomycin in the treatment of experimental endocarditis caused by methicillin-resistant and glycopeptide-intermediate\n                    <i>Staphylococcus aureus<\/i>\n                    strains"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0521-7204","authenticated-orcid":false,"given":"Mar\u00eda-Alexandra","family":"Ca\u00f1as","sequence":"first","affiliation":[{"name":"Hospital Cl\u00ednic of Barcelona, IDIBAPS, University of Barcelona , Barcelona 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