In vivo activity of evernimicin (SCH 27899) against methicillin-resistant Staphylococcus aureus in experimental infective endocarditis

Currently, there exist few satisfactory alternatives to vancomycin for ther apy of serious methicillin-resistant Staphylococcus aureus (MRSA) infection s. We employed a rat model of aortic valve endocarditis to assess the poten tial efficacy of evernimicin (SCH 27899) compared with vancomycin against i nfection with a strain susceptible to both agents (MICs of 0.25 and 0.50 mu g/ml, respectively). Infected animals were assigned to one of three groups: controls (no treatment), evernimicin at 60 mg/kg of body weight by intrave nous (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 l og(10) CFU/g. In both treatment groups, bacterial density within vegetation s was significantly reduced in comparison with control animals that had not been treated. Final colony counts were as follows (mean +/- standard devia tion): 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 act ivity of evernimicin In vivo in an experimental model of severe MRSA infect ion.