ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1657099
This article is part of the Research TopicCombatting bacterial resistance: Novel strategies and therapeutic innovationsView all 3 articles
β-tricalcium Phosphate/Calcium Sulfate Loaded with Contezolid Acefosamil (MRX-4) for Antimicrobial Potency, Prevention and Killing Efficacy of MRSA Biofilm
Provisionally accepted
Nan Jiang1
Xin Zhang2
Zi-Xian Liu3
Hao-Yang Wan1Mou-Zhang Huang4Qing-Rong Lin1
Guan-Qiao Liu1*
Chen Peng5*
Bin Yu1*- 1Nanfang Hospital, Southern Medical University, Guangzhou, China
- 2Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University, Jiangmen, China
- 3Lanzhou University Second Hospital, Lanzhou, China
- 4Ganzhou People's Hospital, Ganzhou, China
- 5Hainan General Hospital, Haikou, China
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Objectives This study aimed to evaluate the antimicrobial potency and duration of contezolid acefosamil (MRX-4) combined with gentamicin against methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vitro. We also compared its performance, when delivered via calcium sulfate (CS) and β-tricalcium phosphate/calcium sulfate (β-TCP/CS) carriers, with the conventional vancomycin + gentamicin regimen. Methods Antibiotic-loaded beads containing MRX-4 + gentamicin (C+G) or vancomycin + gentamicin (V+G) were prepared using CS and β-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). Results C+G demonstrated prolonged antimicrobial activity, maintaining effective ZOIs for at least 40 days, whereas V+G lost activity by day 40 (P < 0.05). Both C+G and V+G significantly prevented biofilm formation and reduced CFUs by >8 logs (P < 0.001), with no significant difference between carrier types. In biofilm eradication assays, both treatments reduced CFUs by 3–4 logs; however, C+G showed superior efficacy over V+G at day 3 (P < 0.01). CLSM confirmed substantial biofilm disruption and bacterial killing in C+G-treated groups. Conclusions MRX-4 combined with gentamicin, delivered via CS and β-TCP/CS carriers, exhibits superior and sustained local antimicrobial efficacy compared to vancomycin, particularly in eradicating MRSA biofilms.
Keywords: Calcium Sulfate, β-tricalcium phosphate/calcium sulfate, MRX-4, MRSA biofilm, In-vitro experiment
Received: 30 Jun 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Jiang, Zhang, Liu, Wan, Huang, Lin, Liu, Peng and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guan-Qiao Liu, Nanfang Hospital, Southern Medical University, Guangzhou, China
Chen Peng, Hainan General Hospital, Haikou, China
Bin Yu, Nanfang Hospital, Southern Medical University, Guangzhou, China
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