In Vitro Antimicrobial Activity of Fosfomycin, Vancomycin and Daptomycin Alone, and in Combination, Against Linezolid-ResistantEnterococcus faecalis

Introduction Enterococcus faecalisis a significant cause of nosocomial infections and is difficult to treat because of intrinsic and acquired resistance to many antibiotics. In addition, the emergence of linezolid-resistantE. faecalis(LZR-Efa) is reducing the choices available for anti-infective therapy. The aim of this study was to examine the in vitro antibacterial effects of fosfomycin (FM), vancomycin (VAN) and daptomycin (DAP), alone and in combination, against LZR-Efa. Methods Five LZR-Efa strains andE. faecalisATCC 29212 were studied. The antibacterial effects of FM, and of FM, VAN and DAP, were assessed using the time-kill assay. Biofilm formation and elimination were evaluated by crystal violet staining. Results When used at concentrations greater than 0.5 x MIC, FM did not produce dose-dependent effects against LZR-Efa isolates. The use of DAP (47.1 mg/L) alone, and FM (83 mg/L) combined with DAP (20.6 mg/L), produced a persistent inhibitory effect against both planktonic LZR-Efa isolates and those forming biofilms. In addition, FM and VAN combined with glucose-6-phosphate produced visible eradication effects against biofilms grown for 24 h, while DAP alone or combined with FM resulted in the best eradication activity against biofilms grown for 72 h prior to exposure. Conclusion The use of FM combined with DAP provided the best potential therapeutic option for treating LZR-Efa infections out of those tested. In addition, the optimum treatment for biofilm elimination depended on the stage of biofilm formation.