Comparative activity of garenoxacin and other agents by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens

Abstract

Objectives: Garenoxacin is a novel des-F(6)quinolone that has shown excellent antimicrobial activity against a wide range of clinically important microorganisms. In this study, its activity was examined, in comparison with that of other antimicrobial agents, by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens. Methods: Overall, 200 bacterial strains were tested. The antimicrobial activity of garenoxacin was compared with that of ciprofloxacin, levofloxacin, moxifloxacin, amoxicillin, co-amoxiclav, cefuroxime, cefotaxime, ceftriaxone, imipenem, erythromycin and clarithromycin. In addition, the bactericidal activity of garenoxacin, moxifloxacin, levofloxacin and ciprofloxacin was evaluated by time-kill analysis against four strains each of staphylococci [two methicillin-susceptible (MSSA) and two methicillin-resistant (MRSA)], pneumococci (two penicillin-susceptible and two penicillin-resistant) and Streptococcus pyogenes (two erythromycin-susceptible and two erythromycin-resistant). Antibiotics were tested at concentrations 1-8 × MIC. Results: MIC90 values of garenoxacin for the MSSA and MRSA strains were 0.03 and 2 mg/L, respectively. Among all the quinolones tested, garenoxacin yielded the lowest MIC values against all pneumococci MIC90 0.12 mg/L) irrespective of macrolide resistance; the rank order of activity was garenoxacin> moxifloxacin>levofloxacin>ciprofloxacin. Excellent activity was shown also against Haemophilus influenzae (MIC90 ≤ 0.03 mg/L) and Moraxella calarrhalis (MIC90 ≤ 0.03 mg/L). Ninety percent of S. pyogenes were inhibited at garenoxacin concentrations equal to 0.25 mg/L, its activity not being influenced by macrolide susceptibility. Garenoxacin was rapidly bactericidal against staphylococci, producing a ≥ 3 log10 decrease in viable counts (cfu/mL) within 3 h at 4 × MIC, whereas a moderate, slower killing rate was observed versus streptococci. Conclusions: This investigational des-F(6)quinolone represents a promising alternative for the treatment of respiratory tract infections.