Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 65, Issue 7, Pages 1441-1447Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkq127
Keywords
fluoroquinolones; time-kill; bactericidal activity
Funding
- Bausch + Lomb, Rochester, NY, USA
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Objectives: Besifloxacin is a novel fluoroquinolone that was recently approved for topical treatment of bacterial conjunctivitis. The compound was shown to be active in vitro against a broad spectrum of bacteria, including isolates resistant to other antibacterials. Here, the bactericidal activity of besifloxacin was evaluated against the most common bacterial conjunctivitis pathogens. Methods: MIC, MBC and time-kill experiments with besifloxacin and comparators were performed according to CLSI guidelines. Quinolone resistance-determining regions (QRDRs) were sequenced using standard PCR-based techniques. Results: MIC and MBC data indicated that besifloxacin was the most potent fluoroquinolone tested against Staphylococcus aureus (n=30), Staphylococcus epidermidis (n=15) and Streptococcus pneumoniae (n=35), while all fluoroquinolones were highly active against Haemophilus influenzae (n=40). Besifloxacin MBC:MIC ratios were <= 4 for 97.5% of all isolates tested (n=120). All fluoroquinolones tested, as well as tobramycin, were bactericidal, while azithromycin was bactericidal against S. pneumoniae and H. influenzae, but bacteriostatic against the staphylococci. Time-kill assays with all four species showed that besifloxacin caused >= 1000-fold killing within 2 h for 11 of 12 isolates. Only one isolate treated with moxifloxacin and three ciprofloxacin-treated isolates achieved the same level of bactericidal activity under the same conditions. Unlike the comparator fluoroquinolones, besifloxacin maintained a high potency and bactericidal activity even against strains that contained multiple mutations in the genes encoding DNA gyrase and topoisomerase IV. Conclusions: Overall, besifloxacin demonstrated rapid bactericidal activity against the four major human pathogens tested here, including isolates that showed in vitro resistance to other fluoroquinolones, beta-lactams, macrolides or aminoglycosides.
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