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 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.
Boucher
H W
HW
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Thauvin-Eliopoulos
C
C
Loebenberg
D
D
Eliopoulos
G M
GM
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D016106:Methicillin Resistance; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C001202:evernimicin; D014640:Vancomycin