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Published on: June 4, 2012

Garenoxacin treatment of experimental endocarditis caused by viridans group streptococci

Paloma Anguita-Alonso1, Mark S Rouse, Kerryl E Piper

  • 1Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.

Antimicrobial Agents and Chemotherapy
|March 30, 2006
PubMed

Insights

Garenoxacin and levofloxacin showed limited efficacy in a rabbit model of Streptococcus endocarditis. Pharmacokinetic/pharmacodynamic ratios may not accurately predict quinolone activity against certain viridans group streptococci.

Area of Science:

  • Pharmacology and Microbiology
  • Infectious Diseases
  • Translational Research

Background:

  • Viridans group streptococci are a common cause of endocarditis.
  • Garenoxacin and levofloxacin are fluoroquinolone antibiotics with broad-spectrum activity.
  • Assessing the efficacy of novel antibiotics in preclinical models is crucial for clinical application.

Purpose of the Study:

  • To compare the in vivo efficacy of garenoxacin, levofloxacin, and penicillin against Streptococcus mitis and Streptococcus sanguinis endocarditis in rabbits.
  • To evaluate the predictive value of pharmacokinetic/pharmacodynamic (PK/PD) indices, such as area under the curve (AUC)/minimum inhibitory concentration (MIC) and maximum concentration of drug in serum (Cmax)/MIC, for garenoxacin and levofloxacin activity.
  • To determine the suitability of garenoxacin and levofloxacin for treating serious infections caused by quinolone-susceptible viridans group streptococci.

Main Methods:

  • A rabbit model of catheter-induced aortic valve endocarditis was established using Streptococcus mitis and Streptococcus sanguinis isolates.
  • Animals were treated with penicillin, garenoxacin, levofloxacin, or left untreated for 3 days.
  • Bacterial titers in cardiac valve vegetations were quantitatively cultured post-treatment to assess antimicrobial activity.

Main Results:

  • All tested antimicrobial agents demonstrated significant activity against Streptococcus mitis endocarditis compared to no treatment.
  • None of the antimicrobial agents showed significant activity against Streptococcus sanguinis endocarditis compared to no treatment.
  • Garenoxacin and levofloxacin exhibited limited efficacy in this experimental model, despite favorable PK/PD ratios for garenoxacin.

Conclusions:

  • AUC/MIC and Cmax/MIC ratios may not reliably predict the activity of certain quinolones in experimental viridans group streptococcal endocarditis.
  • Garenoxacin and levofloxacin may not be optimal choices for treating severe infections caused by some quinolone-susceptible viridans group streptococci.
  • Further research is needed to understand the PK/PD relationships and clinical utility of fluoroquinolones in treating streptococcal endocarditis.

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