High Activity of Fosfomycin and Rifampin against Methicillin-Resistant Staphylococcus aureus Biofilm In Vitro and in an Experimental Foreign-Body Infection Model

• DOI: 10.1128/aac.02420-12
• Publication Date: 2014-02-19T05:16:41Z
• Authors: Raluca Mihailescu; Ulrika Furustrand...; Stéphane Corvec; Alessandra Oliva; Bertrand Betrisey; Oliver Borens; Andrej Trampuz
• Keywords: Fosfomycin; Daptomycin; Tigecycline; Linezolid

ABSTRACT Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, tigecycline against MRSA (ATCC 43300) a foreign-body (implantable cage) infection model. The MICs individual agents were as follows: fosfomycin, 1 μg/ml; 0.125 0.04 tigecycline, μg/ml. Microcalorimetry showed synergistic rifampin at subinhibitory concentrations planktonic biofilm MRSA. In time-kill curves, exhibited time-dependent reduction 2.5 log 10 CFU/ml 128 × MIC. animal model, bacteria cage fluid reduced <1 1.7 2.2 fosfomycin-tigecycline fosfomycin-vancomycin, 3.8 fosfomycin-daptomycin, >6.0 daptomycin-rifampin fosfomycin-rifampin. Daptomycin-rifampin cured 67% cage-associated fosfomycin-rifampin 83%, whereas all single drugs (fosfomycin, tigecycline) rifampin-free combinations no cure infections. No emergence was observed animals; however, 4-fold increase MIC (from 2 to 16 μg/ml) occurred fosfomycin-vancomycin group. summary, highest eradication achieved (83%). Fosfomycin may be used infections, but it cannot replace an antibiofilm agent.