In vitro efficacy of fosfomycin-containing regimens against methicillin-resistant Staphylococcus aureus in biofilms

Objectives: To compare the in vitro antibacterial efficacy of antistaphylococcal antibiotics in combination with fosfomycin or rifampicin, using a biofilm model. Methods: The antibacterial activities of fusidic acid, linezolid, vancomycin, teicoplanin, rifampicin, minocycline, fosfomycin and tigecycline, individually and in fosfomycin or rifampicin combinations, were measured against planktonic or biofilm-embedded methicillin-resistant Staphylococcus aureus (MRSA) with susceptible and resistant breakpoint concentrations (SBCs and RBCs, respectively), using the MTT-staining method and by counting the number of cfu in the biofilms. Results: Linezolid alone at its SBC, and fosfomycin, linezolid, minocycline and tigecycline at their RBCs, exhibited killing effects on biofilm-embedded MRSA (P < 0.0001). Of the eight fosfomycin combinations studied, fosfomycin combined with linezolid, minocycline, vancomycin or teicoplanin at their respective SBCs, exhibited enhanced antibacterial activities (P < 0.0001) when compared with the control group, and outperformed rifampicin combinations (P < 0.01). The killing effects of fosfomycin combinations at their respective RBCs were better than those at their respective SBCs (P < 0.05). Significantly enhanced killing effects were observed with fosfomycin in combination with vancomycin or teicoplanin, compared with vancomycin or teicoplanin alone. For 10 randomly selected MRSA isolates, the results of colony counting in biofilms were comparable with those of the MTT-staining method. Conclusions: Fosfomycin enhanced the activities of linezolid, minocycline, vancomycin and teicoplanin. These combinatorial treatments were even better than rifampicin combination regimens, and may provide therapeutic advantages in catheter-related or prosthetic joint infections.