Enhanced efficacy of sequential administration of fosfomycin and linezolid against methicillin-resistant Staphylococcus aureus

Bibliographic Details
Title: Enhanced efficacy of sequential administration of fosfomycin and linezolid against methicillin-resistant Staphylococcus aureus
Authors: Zaixing Chen, Qin Ai, Shuai Zheng, Ziyan Chen, Sailan Wang, Na Zhang, Huiping Liu, Yanyan Liu, Jiabin Li, Xiaohui Huang
Source: Frontiers in Microbiology, Vol 16 (2025)
Publisher Information: Frontiers Media S.A., 2025.
Publication Year: 2025
Collection: LCC:Microbiology
Subject Terms: linezolid, fosfomycin, sequential administration, MRSA, PK/PD, Microbiology, QR1-502
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-302X
Relation: https://www.frontiersin.org/articles/10.3389/fmicb.2025.1511707/full; https://doaj.org/toc/1664-302X
DOI: 10.3389/fmicb.2025.1511707
Access URL: https://doaj.org/article/89a7125c4dc14a00b818f72cd625314a
Accession Number: edsdoj.89a7125c4dc14a00b818f72cd625314a
Database: Directory of Open Access Journals
More Details
ISSN:1664302X
DOI:10.3389/fmicb.2025.1511707
Published in:Frontiers in Microbiology
Language:English