Synergism of Vancomycin-Gentamicin and Vancomycin-Streptomycin Against Enterococci

Abstract

The in vitro activity of vancomycin and combinations of vancomycin-gentamicin and vancomycin-streptomycin against enterococci was investigated. The minimal inhibitory concentration of vancomycin for 99 of 100 enterococcal strains isolated clinically was 3.12 μg or less/ml. When cultures of eight strains were incubated with vancomycin, regardless of the inoculum size (10 6 , 10 5 , or 10 4 ) and concentration of vancomycin (10 or 20 μg/ml), there was no significant reduction in the number of viable enterococci at 6, 24, and 48 h. Gentamicin and streptomycin in concentrations attainable clinically were not effective against enterococci. Vancomycin combined with gentamicin or streptomycin was tested against 41 enterococcal strains. With the combination of vancomycin at 10 μg/ml and gentamicin at 4 μg/ml or vancomycin at 5 μg/ml and gentamicin at 4 μg/ml, synergism was demonstrated against all 41 strains at 6 h. The combination of vancomycin at 10 μg/ml and streptomycin at 10 μg/ml was only synergistic against 25 of 41 strains at 6 h, and only 22 of 41 strains were affected synergistically at 6 h by vancomycin at 5 μg/ml with streptomycin at 10 μg/ml. With few exceptions, the enhanced killing was more pronounced at 24 and 48 h. The combination of vancomycin and gentamicin or vancomycin and streptomycin (where in vitro studies demonstrate synergism) may be a useful alternate therapy in enterococcal endocarditis.