Therapeutic efficacy of GAR-936, a novel glycylcycline, in a rat model of experimental endocarditis.
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| Abstract |
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 (</=0.12 microgram/ml) in vitro against each of the isolates tested. Endocarditis was established by placement of a catheter across the aortic valve, followed by intravenous injection of 10(6) CFU of bacteria 48 h later. Treatment with GAR-936 or vancomycin was initiated 24 to 36 h after bacterial infection and administered subcutaneously twice a day for 3 days at ascending doses. GAR-936 reduced bacterial vegetation titers by >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.
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| Authors | T M Murphy, J M Deitz, P J Petersen, S M Mikels, W J Weiss |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 44 Issue 11 Pg. 3022-7 (Nov 2000) ISSN: 0066-4804 [Print] United States |
| PMID | 11036017 (Publication Type: Journal Article) |
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