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In vivo activity of evernimicin (SCH 27899) against methicillin-resistant Staphylococcus aureus in experimental
H W Boucher1, C Thauvin-Eliopoulos, D Loebenberg
1Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Abstract:
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.
Insights
Evernimicin shows potential as a treatment for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, demonstrating comparable efficacy to vancomycin in a rat endocarditis model. Further research is warranted for this vancomycin alternative.
Area of Science:
- Infectious Diseases
- Pharmacology
- Microbiology
Background:
- Limited effective therapeutic options exist for severe methicillin-resistant Staphylococcus aureus (MRSA) infections.
- Vancomycin is a primary treatment, but alternatives are needed.
Purpose of the Study:
- To evaluate the efficacy of evernimicin (SCH 27899) against MRSA in a rat model of aortic valve endocarditis.
- To compare evernimicin's effectiveness with vancomycin.
Main Methods:
- A rat model of aortic valve endocarditis was used.
- Animals were treated with either evernimicin (60 mg/kg/day IV), vancomycin (150 mg/kg/day continuous IV), or no treatment.
- Bacterial colony counts in vegetations were measured after 5.5 days of therapy.
Main Results:
- Both evernimicin and vancomycin significantly reduced bacterial density in vegetations compared to controls.
- Evernimicin achieved a mean colony count of 7.22 log(10) CFU/g, while vancomycin achieved 5.65 log(10) CFU/g.
- The difference in efficacy between evernimicin and vancomycin was not statistically significant.
Conclusions:
- Evernimicin demonstrated in vivo bacteriostatic activity against MRSA in a severe infection model.
- Evernimicin represents a potential alternative therapeutic agent for serious MRSA infections.