Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci.
The activity of garenoxacin was compared to that of levofloxacin or penicillin in a rabbit model of Streptococcus mitis group (penicillin MIC, 0.125 microg/ml) and Streptococcus sanguinis group (penicillin MIC, 0.25 microg/ml) endocarditis. Garenoxacin and levofloxacin had MICs of 0.125 and 0.5 microg/ml, respectively, for both study isolates. Rabbits with catheter-induced aortic valve endocarditis were given no treatment, penicillin at 1.2x10(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 (Cmax)/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 Cmax/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.
Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Paloma
P
Anguita-Alonso
Mark S
MS
Rouse
Kerryl E
KE
Piper
James M
JM
Steckelberg
Robin
R
Patel
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013290:Streptococcal Infections / Q000188:drug therapy*; D034363:Viridans Streptococci / Q000187:drug effects
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C419689:garenoxacin