Currently, there exist few satisfactory alternatives to
vancomycin for
therapy of serious methicillin-resistant Staphylococcus aureus (MRSA)
infections. We employed a rat model of aortic valve
endocarditis to assess the potential efficacy of
evernimicin (
SCH 27899) compared with
vancomycin against
infection with a strain susceptible to both agents (MICs of 0.25 and 0.50 microg/ml, respectively). Infected animals were assigned to one of three groups: controls (no treatment),
evernimicin at 60 mg/kg of
body weight by intravenous (i.v.) infusion once daily, or
vancomycin at 150 mg/kg of
body weight per day by continuous i.v. infusion.
Therapy was administered for 5.5 days. At the start of
therapy, colony counts in vegetations were 6.63 +/- 0.44 log(10) CFU/g. In both treatment groups, bacterial density within vegetations was significantly reduced in comparison with control animals that had not been treated. Final colony counts were as follows (mean +/- standard deviation): controls, 10.12 +/- 1.51 log(10) CFU/g of vegetation;
evernimicin, 7.22 +/- 2.91 log(10) CFU/g of vegetation;
vancomycin, 5.65 +/- 1.76 log(10) CFU/g of vegetation. The difference between the
evernimicin and
vancomycin groups was not significant. These results confirmed the bacteriostatic activity of
evernimicin in vivo in an experimental model of severe MRSA
infection.