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

INTRODUCTION: Enterococcus faecalis is 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-resistant E. 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 and E. faecalis ATCC 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 × 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00342-1) contains supplementary material, which is available to authorized users.