{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:10:01Z","timestamp":1758672601008,"version":"3.44.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aimed to evaluate the antimicrobial potency and duration of contezolid acefosamil (MRX-4) combined with gentamicin against methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) biofilms <jats:italic>in vitro<\/jats:italic>. We also compared its performance, when delivered via calcium sulfate (CS) and \u03b2-tricalcium phosphate\/calcium sulfate (\u03b2-TCP\/CS) carriers, with the conventional vancomycin + gentamicin regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Antibiotic-loaded beads containing MRX-4 + gentamicin (C + G) or vancomycin + gentamicin (V + G) were prepared using CS and \u03b2-TCP\/CS carriers. Antimicrobial potency and release duration were assessed using a modified Kirby-Bauer zone of inhibition (ZOI) assay. MRSA biofilm prevention and eradication were evaluated through colony forming unit (CFU) counting and confocal laser scanning microscopy (CLSM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>C + G demonstrated prolonged antimicrobial activity, maintaining effective ZOIs for at least 40 days, whereas V + G lost activity by day 40 (P &amp;lt; 0.05). Both C + G and V + G significantly prevented biofilm formation and reduced CFUs by &amp;gt; 8 logs (P &amp;lt; 0.001), with no significant difference between carrier types. In biofilm eradication assays, both treatments reduced CFUs by 3\u20134 logs; however, C + G showed superior efficacy over V + G at day 3 (P &amp;lt; 0.01). CLSM confirmed substantial biofilm disruption and bacterial killing in C + G-treated groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MRX-4 combined with gentamicin, delivered via CS and \u03b2-TCP\/CS carriers, exhibits superior and sustained local antimicrobial efficacy compared to vancomycin, particularly in eradicating MRSA biofilms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1657099","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T07:56:05Z","timestamp":1758614165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-tricalcium phosphate\/calcium sulfate loaded with contezolid acefosamil (MRX-4) for antimicrobial potency, prevention and killing efficacy of MRSA biofilm"],"prefix":"10.3389","volume":"16","author":[{"given":"Nan","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zi-Xian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-Yang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mou-Zhang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Rong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan-Qiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0078923","DOI":"10.1128\/aac.00789-23","article-title":"Contezolid can replace linezolid in a novel combination with bedaquiline and pretomanid in a murine model of tuberculosis","volume":"67","author":"Almeida","year":"2023","journal-title":"Antimicrob. 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