Selection of glycopeptide-resistant mutants of VanB-type Enterococcus faecalis BM4281 in vitro and in experimental endocarditis

Abstract

Enterococcus faecalis BM4281 is resistant to vancomycin, susceptible to teicoplanin (VanB phenotype), and intrinsically resistant to low levels of gentamicin. The efficacy of glycopeptides against BM4281 was investigated in a rabbit model of experimental endocarditis for reduction of bacterial counts in cardiac vegetations and selection of mutants with increased resistance to glycopeptides. Teicoplanin led to a 100-fold reduction of bacteria in the vegetations, whereas vancomycin had no effect. Monotherapy with either antibiotic selected mutants with homogeneous or heterogeneous resistance to high levels of both glycopeptides. Vancomycin also selected mutants that required the antibiotic for growth. The combination of gentamicin plus teicoplanin was bactericidal, prevented the emergence of mutants, and allowed sterilization of the vegetations in 25% of the rabbits, indicating that the combination may be an alternative if penicillin cannot be used against VanB-type enterococci.