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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1511707
Enhanced Efficacy of Sequential Administration of Fosfomycin and Linezolid Against Methicillin-Resistant Staphylococcus aureus
Provisionally accepted
Zaixing Chen 1
Qin Ai 1
Shuai Zheng 1 Ziyan Chen 2 Sailan Wang 1
Na Zhang 1 Huiping Liu 1 Yanyan Liu 3,4*
Jiabin Li 3,4*
Xiaohui Huang 1*- 1 Department of Pharmacology, Anhui Medical University, Hefei, Anhui Province, China
- 2 Department of Pharmacy, School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, China
- 3 Department of Infectious Diseases, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, China
- 4 Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui Province, China
The aim of this study was to assess the superiority of sequential administration of fosfomycin and linezolid in combination on the efficacy of methicillin-resistant Staphylococcus aureus(MRSA).The antimicrobial activity was assessed using static and dynamic bactericidal assays, along with pharmacokinetics/pharmacodynamics in vitro simulation models. Transmission electron microscopy (TEM) was employed to observe ultrastructural changes in MRSA cell walls following both sequential and concomitant dosing strategies. The results indicated that in the static time-kill assay, at MIC levels (fosfomycin at 4-8 mg/L and linezolid at 2-4 mg/L), the combination effectively inhibited MRSA growth under both concurrent and sequential administration; however, the sequential dosing regimen exhibited significantly greater bactericidal activity. Similarly, in the dynamic sterilization test conducted at clinically relevant doses (linezolid 600 mg and fosfomycin 2 g), a comparable trend was observed, further supporting the superior efficacy of sequential administration.TEM analysis further revealed that sequential dosing caused more extensive damage to the bacterial cell wall and nucleus compared to concomitant administration. These findings suggest that sequential administration of fosfomycin and linezolid enhances in vitro efficacy against MRSA and may provide an improved approach for managing complicated and drug-resistant infections.
Keywords: linezolid, Fosfomycin, sequential administration, MRSA, PK/PD
Received: 15 Oct 2024; Accepted: 17 Feb 2025.
Copyright: © 2025 Chen, Ai, Zheng, Chen, Wang, Zhang, Liu, Liu, Li and Huang. 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:
Yanyan Liu, Department of Infectious Diseases, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, China
Jiabin Li, Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui Province, China
Xiaohui Huang, Department of Pharmacology, Anhui Medical University, Hefei, 230032, Anhui Province, China
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