In Vitro Synergy with Fosfomycin Plus Doxycycline Against Linezolid and Vancomycin-resistant Enterococcus faecium

Linezolid and vancomycin resistant Enterococcus faecium (LRVREF) is globally emerging as a urinary nosocomial pathogen. A decrease in the amount of successful treatment options has created a necessity for the development of novel antimicrobial therapies. Combination therapy may provide an effective alternative for treatment. Fosfomycin and doxycycline are currently used individually for the treatment of urinary tract infections. Fosfomycin has recently seen increased usage due to its persistent activity against a large spectrum of multidrug-resistant organisms. The purpose of this study was to investigate the interaction of fosfomycin plus doxycycline against LRVREF isolates. MICs for fosfomycin and doxycycline were determined for 24 unique clinical LRVREF isolates (4%, fosfomycin-susceptible; 92%, doxycycline-susceptible). In vitro synergy testing with the combination of fosfomycin and doxycycline was performed using an Etest® method and time-kill assay. The combination of fosfomycin and doxycycline demonstrated synergy with the Etest method in 11/24 (46%) isolates and in 10/14 (41%) isolates by time-kill assay. Results from the Etest method and time-kill assay were in agreement for 7/24 (29.2%) of isolates. No antagonism was found. The combination of fosfomycin and doxycycline should be evaluated further with additional LRVREF isolates. In vivo studies should also be performed prior to usage in clinical situations.