〔Abstract〕 Objective The purpose of this study was to investigate the effect of different exposure sequence and interval on the post-antibiotic effect(PAE) and 24-hour time-kill produced by linezolid and fosfomycin in combination againstStaphylococcus aureus(S.aureus). Methods PAEs were evaluated by exposingS.aureusto linezolid and fosfomycin individually and simultaneously for 1 h.Further assess of PAEs with the organism exposed first to linezolid for 1 h, followed by a second 1 h fosfomycin exposure at the beginning(Tb),middle(Tm)and end(Te) of the PAE phase induced by linezolid.The next study was similar to the above, but with the sequence of the two antibiotics reversed, i.e.fosfomycin then linezolid.The 24-hour time-kill studies were performed with three exposure regimens: simultaneous exposure of the two antibiotics; first exposure to linezolid for 1 h and then combined with fosfomycin, and first exposure to fosfomycin for 1 h and then combined with linezolid to draw the sterilized curve. Results Compared with the PAE of individual antibiotics [ linezolid(1.2±0.1) h, fosfomycin(1.6±0.1) h],the PAE produced by simultaneous exposure of the combination(2.9±0.1) h presented additive interaction.However, the PAE of fosfomycin decreased or even disappeared(-0.3 h for Tb, 0 h for Tm and 0.9 h for Te) during the PAE phase of linezolid, and with a stronger antagonism at the beginning.Differently, an additive interaction was observed again when the test organism was exposed to fosfomycin first.In the 24-hour time-kill assays, the antibacterial effect of the first exposure to fosfomycin regimens was significantly stronger(difference of 1 log10)than that of the simultaneous exposure and the first exposure to linezolid, while the latter two were similar. Conclusion The pharmacodynamic behaviour of linezolid combined with fosfomycin againstS.aureuswas influenced by exposure regimen.The first exposure to fosfomycin regimens rather than simultaneous exposure may exert the optimal antibacterial activity.Therefore, the exposure regimen is one of the important factors to be considered for the clinical application of this combination.