Infection and Drug Resistance (Dec 2023)
Fosfomycin Enhances the Inhibition Ability of Linezolid Against Biofilms of Vancomycin-Resistant Enterococcus faecium in vitro
Abstract
Jie Chi,1 Yaowen Li,2,3 Na Zhang,2,3 Huiping Liu,2,3 Zhifeng Chen,1 Jiabin Li,4 Xiaohui Huang2,3 1Department of Pharmacy, Tongling Municipal Hospital, Tongling, Anhui, People’s Republic of China; 2Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Xiaohui Huang, Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Meishan Road 81#, Hefei, Anhui, 230032, People’s Republic of China, Tel +86 138 5518 3138, Email [email protected]: We explored the inhibition ability of linezolid/fosfomycin combination against biofilms of vancomycin-resistant Enterococcus faecium (VREfm) and tried to provide a theoretical basis for the treatment of VREfm biofilm-associated infections.Methods: Four clinical isolates of VREfm (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 VREfm 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 cylA, ebpA, and gelE transcription in VREfm in the initial and mature stages. To the mature biofilm, the combination also reduced the expression of asa1, atlA, and esp.Conclusion: The combination of linezolid and fosfomycin represented stronger inhibitory effect on the biofilm formation of VREfm than linezolid alone.Keywords: linezolid, fosfomycin, biofilm-formation genes, vancomycin-resistant Enterococcus faecium
