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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Therapeutic efficacy of GAR-936, a novel glycylcycline, in a rat model of experimental endocarditis. 1103 17

The activity of tigecycline (GAR-936), a novel glycylcycline, was investigated in vitro and in experimental endocarditis due to the susceptible Enterococcus faecalis JH2-2 strain, its VanA type transconjugant BM4316, and a clinical VanA type strain, E. faecium HB217 resistant to tetracycline. MICs of GAR-936 were 0.06 micro g/ml for the three strains. In vitro pharmacodynamic studies demonstrated a bacteriostatic effect of GAR-936 that was not enhanced by increasing concentrations to more than 1 micro g/ml and a postantibiotic effect ranging from 1 to 4.5 h for concentrations of 1- to 20-fold the MIC. Intravenous injection of [(14)C]GAR-936 to five rabbits with enterococcal endocarditis sacrificed 30 min, 4 h, or 12 h after the end of the infusion evidenced a lower clearance of GAR-936 from aortic vegetations than from serum and a homogeneous diffusion of GAR-936 into the vegetations. In rabbits with endocarditis, GAR-936 (14 mg/kg of body weight twice a day [b.i.d.]) given intravenously for 5 days was bacteriostatic against both strains of E. faecalis. Against E. faecium HB217, bacterial counts in vegetations significantly decreased during therapy (P < 0.01), and the effect was similar with GAR-936 at 14 mg/kg b.i.d., 14 mg/kg once a day (o.d.), and 7 mg/kg o.d., which provided concentrations in serum constantly above the MIC. Mean serum elimination half-life ranged from 3.3 to 3.6 h. No GAR-936-resistant mutants were selected in vivo with any regimen. We concluded that the combination of prolonged half-life, significant postantibiotic effect, and good and homogeneous diffusion into the vegetations may account for the in vivo activity of GAR-936 against enterococci susceptible or resistant to glycopeptides and tetracyclines, even when using a o.d. regimen in rabbits.
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PMID:Activity and diffusion of tigecycline (GAR-936) in experimental enterococcal endocarditis. 1249 94

Viridans group streptococci including Streptococcus gallolyticus (formerly S. bovis) represent serious invasive pathogens often associated with endocarditis or sepsis among immunocompromised or cancer patients. Tigecycline (GAR-936), the first clinically studied glycylcycline, has a potent gram-positive activity with a potential treatment option for these streptococcal infections. The studied collection (848 strains) included 100 isolates each of Streptococcus anginosus, Streptococcus constellatus, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis, Streptococcus salivarius, Streptococcus sanguis, and fewer strains of S. gallolyticus (98 strains) and Streptococcus mutans (50 strains). These strains were isolated from patients on 3 continents in the SENTRY Antimicrobial Surveillance Program and tested for susceptibility and interpreted by Clinical and Laboratory Standards Institute broth microdilution methods and criteria (< or = 0.25 microg/mL for tigecycline per US Food and Drug Administration). Penicillin susceptibility rates for the entire collection varied from 61% (S. sanguis) to 98% (S. constellatus), and macrolide susceptibility was also compromised (49-88%; average, 69%). Tigecycline was active against all isolates tested, in contrast to tetracycline resistance rates of 8-66%, and highest for S. gallolyticus. In conclusion tigecycline was quite active against bacteremic isolates of viridans group streptococci species and S. gallolyticus with an overall MIC90 at < or = 0.06 microg/mL; the highest MIC was only 0.25 microg/mL.
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PMID:Tigecycline (GAR-936) activity against Streptococcus gallolyticus (bovis) and viridans group streptococci. 1698 74