Therapeutic efficacy of GAR-936, a novel glycylcycline, in a rat model of experimental endocarditis

GAR-936, a novel glycylcycline, was investigated with a rat model of experimental endocarditis. It was compared with vancomycin against both vancomycin-susceptible and -resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus. GAR-936 exhibited the lowest MICs (2 log(10) CFU, compared to those in untreated controls, for both vancomycin-susceptible and -resistant (VanA and VanB) E. faecalis strains and >4 log(10) CFU for a methicillin-resistant S. aureus isolate. The glycylcycline was more efficacious at a lower administered dose in the rat model of endocarditis than was vancomycin. The efficacy of GAR-936 in this model was apparently not enhanced by a factor in rat serum, as was observed for vancomycin with a time-kill curve. The results of this study demonstrate the therapeutic potential of GAR-936 for the treatment of enterococcal and staphylococcal infections and warrant further investigation.