Bactericidal activity of besifloxacin against staphylococci, Streptococcus pneumoniae and Haemophilus influenzae.
OBJECTIVE
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 < or = 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 > or = 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.
Haas
Wolfgang
W
Bausch + Lomb, Inc., Rochester, NY 14609, USA. wolfgang.haas@bausch.com
Pillar
Chris M
CM
Hesje
Christine K
CK
Sanfilippo
Christine M
CM
Morris
Timothy W
TW
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D003231:Conjunctivitis / Q000382:microbiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005798:Genes, Bacterial; D006193:Haemophilus influenzae / Q000187:drug effects*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D017422:Sequence Analysis, DNA; D013210:Staphylococcus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013997:Time Factors; D047090:beta-Lactams / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001381:Azepines; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D018942:Macrolides; D047090:beta-Lactams; C522124:besifloxacin