In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of Staphylococcus aureus Hao Chen,1–3,* Lan Li,2,3,* Yanyan Liu,4 Maomao Wu,2,3 Shuangli Xu,2,3 Guijun Zhang,2,3 Caifen Qi,2,3 Yan Du,2,3 Mingli Wang,5 Jiabin Li,4 Xiaohui Huang2,3 1Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; 2Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China; 3Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China; 4Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; 5Department of Microbiology, Anhui Medical University, Hefei, Anhui, China *These authors contributed equally to this work Objectives: Linezolid combination therapy is recommended for the treatment of Staphylococcus aureus (S. aureus) infections. However, the optimal regimen of the combination therapy for S. aureus is unknown. The objective of this study was to investigate the antibacterial activity, post-antibiotic effect (PAE), and post-antibiotic subminimum inhibitory concentration (MIC) effect (PA-SME) of linezolid alone and in combination with fosfomycin against eleven clinical isolates of S. aureus.Methods: The synergistic effects and antibacterial activity of linezolid and fosfomycin were assessed by checkerboard and time-kill assays. To determine the PAE and PA-SME, S. aureus strains in the logarithmic phase of growth were exposed for 1, 2, and 3 hours to the antibiotics, alone and in combination. Recovery periods of test strains were evaluated using viable counting after dilution.Results: Synergistic effects were observed for eight strains and no antagonism was found with any combination. Moreover, linezolid combined with fosfomycin at 4x MIC showed the best synergistic antibacterial effect, and this effect was retained after 24 hours. In addition, both the antibiotics alone and in combination showed increased PAE and PA-SME values in a concentration- and time-dependent manner.Conclusion: Linezolid combined with fosfomycin exerted a good antibacterial effect against S. aureus, and the combinations have significant PAE and PA-SME. Keywords: linezolid, fosfomycin, PAE, PA-SME, combination