Garenoxacin Treatment of Experimental Endocarditis Caused by Viridans Group Streptococci

Abstract

The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 g/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 g/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 g/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2 ؋ 10 6 IU/8 h intramuscularly, garenoxacin at 20 mg/kg of body weight/12 h intravenously, or levofloxacin at 40 mg/kg/12 h intravenously. For both isolates tested, garenoxacin area under the curve (AUC)/MIC and maximum concentration of drug in serum (C max )/MIC ratios were 368 and 91, respectively. Rabbits were sacrificed after 3 days of treatment; cardiac valve vegetations were aseptically removed and quantitatively cultured. For S. mitis group experimental endocarditis, all studied antimicrobial agents were more active than no treatment (P < 0.001), whereas for S. sanguinis group endocarditis, no studied antimicrobial agents were more active than no treatment. We conclude that AUC/MIC and C max /MIC ratios may not predict activity of some quinolones in experimental viridans group endocarditis and that garenoxacin and levofloxacin may not be ideal choices for serious infections caused by some quinolone-susceptible viridans group streptococci.

Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon In Vitro Exposure to Daptomycin

“…Samples were obtained from broth (0.5 ml from each infection model), through the injection port, at 0.5, 1, 2, 4, 8, 24, 32, 48, and 72 h for determination of the antibiotic concentrations based on a pharmacodynamic model (SEVM or SBM). Samples were also taken from the homogenized SEVs obtained at 0, 8,24,32,48, and 72 h for determination of the antibiotic concentration within the vegetation. Samples were stored at Ϫ70°C until analysis.…”

“…An aliquot of this suspension was added to the model to produce an initial inoculum of approximately 1 ϫ 10 6 CFU/ml. Colony counts were measured at 0 (baseline), 8,24,32,48, and 72 h after introduction of antibiotic. Bacterial density in CFU/ml was calculated after 24 h of incubation at 35°C.…”