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Besifloxacin, a Novel Fluoroquinolone, Has Broad-Spectrum In Vitro Activity against Aerobic and Anaerobic Bacteria

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Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 07/2009; 53(8):3552-60. DOI: 10.1128/AAC.00418-09
Source: PubMed

ABSTRACT The antibacterial spectrum of besifloxacin, a novel fluoroquinolone recently approved for treatment of ocular infections, was studied using 2,690 clinical isolates representing 40 species. Overall, besifloxacin was the most potent agent tested against gram-positive pathogens and anaerobes and was generally equivalent to comparator fluoroquinolones in activity against most gram-negative pathogens. Besifloxacin demonstrated potent, broad-spectrum activity, which was particularly notable against gram-positive and gram-negative isolates that were resistant to other fluoroquinolones and classes of antibacterial agents.

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Available from: Timothy W Morris, Feb 05, 2014
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    • "MIC values for besifloxacin, moxifloxacin, gatifloxacin, and ciprofloxacin against S. aureus, E. faecalis, E. coli, and P. aeruginosa were within the quality control ranges suggested by CLSI.10 The MIC data for the ATCC quality control strains of E. faecalis, S. aureus, S. pneumoniae, E. coli, and P. aeruginosa were similar to previously published MIC values for besifloxacin, moxifloxacin, MCl, and gatifloxacin.5,8,14–18 Little has been published about the antibacterial potency of GCl, and no manuscripts that describe the antibacterial potency of BMO have been identified in the literature.7 "
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    ABSTRACT: Previous work has shown that besifloxacin, an 8-chloro-fluoroquinolone, has more potent activity against gram-positive pathogens than moxifloxacin and gatifloxacin, which carry an 8-methoxy group. This study was conducted to determine the contribution of the R7 and R8 substituent to fluoroquinolone antibacterial activity. Besifloxacin, moxifloxacin, gatifloxacin, their R8 structural analogs, and ciprofloxacin were tested against representative isolates of various gram-positive and gram-negative species and previously characterized fluoroquinolone-resistant mutants of Staphylococcus aureus. Minimum inhibitory and minimum bactericidal concentrations were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Reserpine was used to determine the effect of efflux pumps on antibacterial activity. In general, exchanging the R8 residue in besifloxacin slightly reduced the molecule's potency, while introducing an 8-chloro group in moxifloxacin increased its potency. A similar change in gatifloxacin had little to no effect. Substituting the R8 residues did not increase the susceptibility to the efflux pump inhibitor reserpine or result in a loss of bactericidal activity. In contrast, the positive control, ciprofloxacin, was shown to be a substrate for reserpine and lost bactericidal activity against some fluoroquinolone-resistant isolates of S. aureus. The data presented here show that, depending on the R7 substituent, replacing an 8-methoxy group with an 8-chloro substituent can improve potency or can have little-to-no effect. These findings highlight the importance of the interplay between the R7 and R8 substituents in determining antibacterial potency.
    Clinical ophthalmology (Auckland, N.Z.) 05/2013; 7:821-30. DOI:10.2147/OPTH.S44085
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    • "Besifloxacin (7-[(3R)-3-aminohexahydro-1Hazepin- 1-yl]-8-chloro-1-cyclopropyl-6-fluoro-1,4- dihyrdo-4-ixi-3-quinolinecarboxylic acid) has a novel C8 chlorine group and C7 amino-axepinyl group (Fig. 1) that are thought to increase potency and increase broad spectrum activity.17 Besifloxacin has shown to have broad spectrum activity against grampositive, gram-negative and anaerobic bacteria.18 "
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    ABSTRACT: Objective To outline the pharmacodynamics, efficacy and safety of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis. Quality of Evidence MEDLINE database was searched to review recent pharmacodynamic and clinical studies evaluating besifloxacin and comparing besifloxacin to other topical antibiotics for ophthalmic use. Findings were limited to full-text articles from clinical journals in the English language. Main Message Bacterial resistance is a common source for treatment failure in bacterial conjunctivis. Besifloxacin, a novel fourth generation synthetic fluoroquinolone is likely to show lower resistance rates due to its mechanism of action and its short-term use for ocular infections only (decreased systemic exposure). Besifloxacin displays improved pharmacodynamic properties compared to other commonly used fluoroquinolones and has shown to be efficacious and safe in clinical studies. Conclusion Besifloxacin ophthalmic suspension 0.6% provides safe and efficacious treatment for bacterial conjunctivitis. The factors leading to bacterial resistance are diminished, which allows besifloxacin to be a favorable treatment option.
    Opthalmology and Eye Diseases 03/2011; 3(3):7. DOI:10.4137/OED.S4102
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    • "Compared with FQS isolates, MIC values for FQR isolates generally increased to a lesser degree for besifloxacin than for the other fluoroquinolones tested. This trend of improved activity against FQR isolates was observed for various species of streptococci, staphylococci, Enterobacteriaceae, pseudomonads and Haemophilus sp.2 "
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Antimicrobial Chemotherapy 07/2010; 65(7):1441-7. DOI:10.1093/jac/dkq127 · 5.44 Impact Factor
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