The Efficacy Of Linezolid/fosfomycin Combination Therapy In Vitro And In A Galleria Mellonella Model Of Staphylococcus Aureus Infection

Objective: To investigate the antibacterial activity of linezolid and fosfomycin against Staphylococcus aureus in vitro and in Galleria mellonella model.Methods: The study antibiotic MICs were determined by broth microdilution.antibacterial activity of linezolid combination with fosfomycin in vitro.The checkerboard method was used to determine if synergistic effects of linezolid and fosfomycin were used in vitro.Combined with the time-skill curve method,the antibacterial activity of the two drugs alone and in combination was evaluated in vitro.To investigate the virulence of 4 S.aureus strains,we injected different concentrations of live bacteria into the hemolymph of each Galleria mellonella larva.To test the protective effect of different antibiotics administration(linezolid,fosfomycin,linezolid/fosfomycin),we injected those drugs into G.mellonella and finally observe its survival rate.Hemolymph load was measured at different time points after administration of G.mellonella to evaluate the antibacterial effect of different modes of administration in vivo.Results: The chequerboard assay and time-kill methodology showed that linezolid and fosfomycin had a synergistic antibacterial effect against Staphylococcus aureus in vitro.Larvae infected with 80% lethal dose of S.aureus,combination therapy compared with single drug has a better therapeutic effect,the efficacy of the antibiotics in vivo closely correlated with the measured in vitro sensitivities.Compared with single drug,the combination of two drugs can reduce the hemolymph load of larvae more rapidly and steadily,which is consistent with the time-kill curve in vitro.Conclusion: Synergistic effect of linezolid with fosfomycin against Staphylococcus aureus in vitro and in an experimental Galleria mellonella model.An 80% lethal dose of Staphylococcus aureus established a G.mellonella infection model can be used as an animal model in antimicrobial activity.Low doses of linezolid combination with fosfomycin compared to monotherapy may have better antibacterial activity.