Fosfomycin Enhances the Inhibition Ability of Linezolid Against Biofilms of Vancomycin-Resistant in Vitro

Purpose: We explored the inhibition ability of linezolid/fosfomycin combination against biofilms of vancomycin-resistant (VRE) and tried to provide a theoretical basis for the treatment of VRE biofilm-associated infections.

Methods: Four clinical isolates of VRE (No.2, No.4, No.5, and No.6) were used for this study, which were collected from the First Affiliated Hospital of Anhui Medical University. The checkerboard method was used to assess the synergistic effect of linezolid and fosfomycin. The inhibition ability of biofilm biomass was evaluated by crystal violet staining, and the metabolic activity was tested by an Alamar blue cell viability assay. Changes in biofilm formation-related genes of the strains after incubating with drugs were investigated via the quantitative real-time polymerase chain reaction (RT-qPCR).

Results: The fractional inhibitory concentration index (FICI) showed that linezolid combined with fosfomycin had a synergistic effect on all four VRE isolates. Compared with linezolid monotherapy, linezolid combined with fosfomycin led to a significant decrease in biofilm biomass and metabolic activity, especially in the mature biofilm. The results of RT-qPCR showed linezolid combined with fosfomycin inhibition biofilm formation through the inhibition of , and transcription in VRE in the initial and mature stages. To the mature biofilm, the combination also reduced the expression of , and .

Conclusion: The combination of linezolid and fosfomycin represented stronger inhibitory effect on the biofilm formation of VRE than linezolid alone.