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

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.Bacterial conjunctivitis is an inflammation of the transparent mucous membrane covering the globe of the eye. This common ocular surface infection is caused by a broad variety of bacteria and is usually treated with broad-spectrum topical ophthalmic antibacterials (1,13,19,20). The increasing prevalence of drug-resistant ocular isolates highlights the need for the development of new agents for the treatment of bacterial infections (8). Besifloxacin ( Fig. 1) is a novel 8-chloro-fluoroquinolone agent with potent, bactericidal activity against prevalent and drug-resistant pathogens (6). Clinical development of the agent for use as a topical ophthalmic agent has been completed, and the agent has demonstrated consistent safety and efficacy in three bacterial conjunctivitis clinical trials (14,16,21). Pharmacokinetic studies demonstrated that after a single topical dose of 0.6% besifloxacin ophthalmic suspension, mean besifloxacin levels in human tears ranged from 610 g/ml at 10 min postadministration to 1.6 g/ml at 24 h postadministration (12). Here, the in vitro activity of besifloxacin against a broad range of aerobic and anaerobic bacterial species, including problematic drug-resistant strains, was evaluated.Totals of 2,535 aerobic and 155 anaerobic bacterial clinical isolates from Eurofins Medinet (Chantilly, VA) were selected for the study. The majority of isolates were from 2005 to 2008, and wherever possible, isolates were from ocular and respiratory specimens of U.S. origin. Susceptibility testing was conducted per Clinical and Laboratory Standards Institute reference methods (9-11).Activity of besifloxacin against gram-positive aerobes. Against Enterococcus faecalis and E. faecium, including vancomycin-resistant enterococci, besifloxacin was more potent than the comparator fluoroquinolones, as well as azithromycin, vancomycin, and tobramycin (Table 1). Besifloxacin further demonstrated excellent activity against Listeria monocytogenes, similar to that of tobramycin and penicillin and better than that observed with comparator fluoroquinolones.For Staphylococcus aureus and S. epidermidis, previously reported MIC 50 s/MIC 90 s were consistent with current besifloxacin values for quinolone-susceptible and quinolone-resistant subsets (3,5,14). Besifloxacin was especially potent against ciprofloxacin-resistant isolates; for example, the MIC 90 s for non-ciprofloxacin-susceptible S. aureus were 4 g/ml for...

Clinical outcomes with besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis due to potentially consequential pathogens

“…In comparison, ciprofloxacin resistance was observed in a much smaller proportion of methicillin-sensitive S. aureus and S. epidermidis strains (9% and 15%, respectively). In agreement with previous studies, 6,31,32,41 besifloxacin demonstrated potent in vitro activity against methicillin-resistant staphylococcal isolates, with MIC 90 values against CipR-MRSA and CipR-MRSE at least eight-to 128-fold lower than that of other fluoroquinolones and comparable to that reported for vancomycin in recent surveillance studies (1-2 µg/mL). …”

“…28,29 Many of these methicillin-resistant strains showed concurrent resistance to other non-β-lactam antibiotics, including aminoglycosides, macrolides, tetracyclines, and/or fluoroquinolones, making the treatment of ocular infections caused by these pathogens a challenge. [24][25][26][27][28][29][30][31][32][33] Although conjunctivitis infections with methicillin-resistant staphylococci are generally not vision-threatening, 24 potentially catastrophic complications have been reported with other ocular infections involving such organisms (eg, keratitis, cellulitis, endophthalmitis). [34][35][36] Topical fluoroquinolones are often used in the treatment of bacterial conjunctivitis due to their low toxicity, broad spectrum of activity, and bactericidal activity.…”

“…40 This balanced activity, in turn, results in broad-spectrum in vitro activity, including activity against P. aeruginosa, S. marcescens, and Neisseria spp., as well as ciprofloxacin-resistant (CipR) and methicillin-resistant staphylococcal isolates. 6,31,32,41,42 The ophthalmic formulation of besifloxacin, which contains 0.663% besifloxacin hydrochloride or 0.6% besifloxacin free base (Besivance ® ; Bausch + Lomb, Bridgewater, NJ, USA) 39 is formulated with DuraSite ® (InSite Vision, Alameda, CA, USA), a mucoadhesive polycarbophil polymer designed to prolong a drug's residence time on the ocular surface and improve bioavailability. [43][44][45][46] DuraSite has also been reported to inhibit staphylococcal biofilm formation in vitro.…”

Topoisomerase Mutations That Are Associated with High-Level Resistance to Earlier Fluoroquinolones in <i>Staphylococcus aureus</i> Have Less Effect on the Antibacterial Activity of Besifloxacin

“…The increasing resistance of S. aureus to many drug classes, including fluoroquinolones, has resulted in the emergence of multidrug-resistant strains, emphasizing the need for new antimicrobial agents. Besifloxacin is a novel 7-azepinyl-8-chloro-fluoroquinolone that has shown improved in vitropotency as well as clinical efficacy against numerous ophthalmic pathogens [1,2,3,4]. It has recently been approved in the United States as besifloxacin ophthalmic suspension, 0.6% (Besivance®) for the topical treatment of bacterial conjunctivitis.…”

Biosynthesis of the Antibiotic Nonribosomal Peptide Penicillin in Baker’s Yeast

“…http://dx.doi.org/10.1101/075325 doi: bioRxiv preprint first posted online Sep. 15, 2016; bioactivity. The secreted levels of benzylpenicillin are similar to those required for antibiotic action against various bacteria such as Streptococcus pyogenes 19 . Therefore, to test the bioactivity of the secreted benzylpenicillin, we diluted liquid cultures of S. pyogenes with spent culture media from either Sc.P2 or from an inactivated version of Sc.P2 (Sc.P2x) that does not produce benzylpenicillin (Fig 3a).…”