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: 4.48). 07/2009; 53(8):3552-60. DOI: 10.1128/AAC.00418-09
Source: PubMed


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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    • "topoisomerase IV enzymes which are essential for the synthesis and replication of bacterial DNA, and this activity is enhanced by a C-8 chloride substituent in besifloxacin. Therefore, it displays potent efficacy against a wide range of Gram-positive and Gram-negative ocular pathogens, including multidrug-resistant strains [3] [4] [5] [6]. Besifloxacin is the only fluoroquinolone not used for systemic infections but specifically developed for ophthalmic use, which makes it unique in its class and theoretically reduces the risk for the development of resistance due to decreased systemic exposure [7]. "
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    ABSTRACT: Besifloxacin is a fourth-generation broad-spectrum fluoroquinolone registered for the topical treatment of bacterial conjunctivitis. In this study, a rapid, sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for quantification of besifloxacin in rabbit plasma and ocular tissues using nateglinide as the internal standard (IS). The analyte and IS were separated on a Sepax GP-Phenyl column by isocratic elution with methanol-acetonitrile-5mM ammonium formate-formic acid (29:55:16:0.1, v/v/v/v) as the mobile phase at a flow rate of 1.2mL/min, and the total run time was 3.0min. An electrospray ionization (ESI) source was applied and operated in the positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification, and the monitored transitions were 394.2→377.1 for besifloxacin and m/z 318.3→166.1 for the IS. The calibration curve was linear over the range of 0.103-206ng/mL for plasma and 2.06-2060ng/mL for tears, aqueous humor, conjunctiva and cornea with correlation coefficient (r) greater than 0.99. The lower limit of quantification (LLOQ) for besifloxacin was 0.103ng/mL for plasma and 2.06ng/mL for other ocular tissues with good accuracy and precision. Intra- and inter-batch precision were both lower than 15% and accuracy ranged from 85% to 115% at all QC levels. The method was successfully applied to the pharmacokinetic study of besifloxacin in rabbit plasma and ocular tissues after single and multiple topical administrations. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Aug 2015 · Journal of pharmaceutical and biomedical analysis
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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.
    Full-text · Article · May 2013 · Clinical ophthalmology (Auckland, N.Z.)
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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.
    Full-text · Article · Mar 2011 · Opthalmology and Eye Diseases
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