August 2009




Fluroquinolones, new and old …

by Matt Young EyeWorld Contributing Editor


The new fluoroquinolone fits into the group of newer antibiotics, like those above.

Perform a literature search in PubMed for “besifloxacin”—Bausch & Lomb’s (Rochester, New York) new fluoroquinolone for the treatment of ocular infections—and you’ll only find search results for studies dating back to 2007. That’s because besifloxacin (Besivance) really is new, and more than in the sense that it was recently approved by the Food and Drug Administration in May for bacterial conjunctivitis, according to John D. Sheppard, M.D., professor of ophthalmology, microbiology and immunology, Eastern Virginia Medical School, Norfolk, Va..

“It has a unique history in that it never has been used before medicinally in any living organism other than in patients in studies that helped it get approved for the treatment of conjunctivitis,” Dr. Sheppard said. “You won’t find it in animal food or in human medicine systemically.” Of course, there always has been plenty of protracted discussion surrounding fluoroquinolones, from determining the “generation” within which they fall, to assessing their true potency. Being the newest fluoroquinolone on the antibiotic block has its pros and cons, as advocates have suggested unrivaled potency advantages, while detractors point to it being unproven. While it’s difficult to relay “just the facts” about besifloxacin with so many diverse opinions, what can be said is that besifloxacin is joining the ophthalmic armamentarium in the fight against ocular infection. It is therefore a highly appropriate time to discuss this new drug in relation to what’s already out there on the market.

Drug with a difference?

Advocates of besifloxacin note that it is a novel 8-chloro fluoroquinolone. “It’s the only fluoro-chloro fluoroquinolone,” Dr. Sheppard said. “It has the most powerful molecular adaptations to give it the best solubility and best spectrum of activity. Those are key issues with any antibiotics.”

A study in the March 2009 issue of Clinical Therapeutics, which was supported by research grants from Bausch & Lomb, showed it to be the “most potent agent tested against gram-positive pathogens and anaerobes, and [it] was generally equivalent to comparator fluoroquinolones against most gram-negative pathogens.” Besifloxacin was studied using 2940 clinical isolates of 40 species. It was compared with moxifloxacin, gatifloxacin, and other antibiotics. Still, Dr. Sheppard is opposed to classifying besifloxacin as a certain “generation” fluoroquinolone because he suggests generation naming comes more from marketing pressures than science or medicine. “We’re not being so presumptuous as to call it a second, third, fourth, fifth, or tenth generation fluoroquinolone,” Dr. Sheppard said. “It simply has unique adaptations.”

For one, it uses a proven delivery vehicle—DuraSite (InSite Vision, Alameda, Calif.)—which is a gel forming drop that according to its manufacturers, “extends the residence time of the drug relative to conventional eye drops.” “It stays on the surface of the eye for a long time,” Dr. Sheppard said. “You get a long duration of drug concentration for the conjunctiva and cornea and aqueous.”

Besifloxacin has also improved performance in overcoming methicillin resistance, Dr. Sheppard said. “Some patients are more prone to develop methicillin resistance,” Dr. Sheppard said. “We have shown a superior drug profile against methicillin-resistant organisms from in vitro data and forthcoming in vivo data. There is going to be a niche for this as the trend of community-acquired methicillin resistance is growing rapidly.” The 0.6% concentration of besifloxacin also boosts concentration levels compared to many previous antibiotics on the market, Dr. Sheppard said. “You know you’re going to get good concentration in the tissues,” Dr. Sheppard said.

With some antibiotic drops, all a patient has to do is blink and the drug concentration is gone, Dr. Sheppard said. “This stuff gloms on there; its viscous nature coats the eye,” Dr. Sheppard said.

Same old same old?

Meanwhile, Francis S. Mah, M.D., co-medical director, Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh School of Medicine, Pennsylvania, has a very different opinion of besifloxacin. “As far as the product itself, it is kind of older,” Dr. Mah said. “We actually looked at it in our lab close to 8 to 10 years ago.”

That said, Dr. Mah suggested that besifloxacin still hasn’t been thoroughly vetted. “We don’t know a lot about its safety profile except to say that it’s a fluoroquinolone, which has been a safe and effective product in the eye,” Dr. Mah said.

Much research is left to be done to determine organism susceptibility or resistance to the drug, he added. Dr. Mah suspects that if an organism is resistant to another fluoroquinolone, it likely would be resistant to besifloxacin as well. “A fluoroquinolone is a fluoroquinolone,” Dr. Mah said. Dr. Mah did acknowledge a few positive points about besifloxacin. First, it is in a relatively high concentration, he said. “It’s the second-highest concentration we have seen in a fluoroquinolone after Iquix [Vistakon Pharmaceuticals, Jacksonville, Fla.],” Dr. Mah said. Iquix comes in a 1.5% levofloxacin concentration. Dr. Mah, however, is not convinced that besifloxacin achieves higher tissue concentrations. “Based on ARVO [Association for Research in Vision and Ophthalmology] peer-reviewed abstracts, because of the 0.6% concentration and DuraSite, besifloxacin achieves extremely high concentrations in the tears,” Dr. Mah said. “There is a reduction in concentration in the tissue though. The conjunctiva concentration is significantly lower and similar to what we have available with moxifloxacin, gatifloxacin and levofloxacin. It may be that the solubility of the drug is actually pretty low itself.”

Besifloxacin “has, in general, shown to be more potent than moxifloxacin [Vigamox, Alcon, Fort Worth, Texas] and gatifloxacin [Zymar, Allergan, Irvine, Calif.] for gram positive organisms in in-vitro testing,” Dr. Mah said. Although moxifloxacin, gatifloxacin and besifloxacin are similar agents, besifloxacin has a slight advantage in terms of minimum inhibitory concentration (MIC), Dr. Mah said. Based on its potency and gram-positive coverage, besifloxacin could be called a fourth-generation fluoroquinolone in Dr. Mah’s view. “I wouldn’t go as far to say it’s a fifth-generation fluoroquinolone myself,” he said. Keep in mind that besifloxacin has its weaknesses, Dr. Mah said. “Moxifloxacin and gatifloxacin would get higher concentrations into the anterior chamber than besifloxacin,” Dr. Mah said.

“Moxifloxacin has the highest concentrations in the anterior chamber and cornea as compared to any of the fluoroquinolones. So I don’t think it’s time to throw away moxifloxacin and gatifloxacin. Those agents continue to have unique properties.”

Similar fluoroquinolone, different options

Mark Packer, M.D., clinical associate professor of ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Ore., meanwhile suggested that while besifloxacin is technically similar to other fluoroquinolones, it has been approved at a unique time in ophthalmology history, when free post-op eye surgery kits, which arguably gave certain manufacturers a stronghold on which antibiotics and other drugs were being used, are being eliminated resulting from new industry guidelines. Regarding similarities, like moxifloxacin and gatifloxacin, besifloxacin inhibits both DNA gyrase and topoisomerase IV, requiring two genetic mutations for bacteria to develop drug resistance, Dr. Packer noted. “But with the introduction of Besivance and more options for post-op care, we may have better options overall in terms of drugs at our disposal,” Dr. Packer said. Dr. Packer, for instance, has been in talks with a local pharmacy to provide custom post-op kits on behalf of his clinic. Hypothetically speaking, such pharmacy-provided (as opposed to manufacturer-provided) kits could include Bausch & Lomb’s besifloxacin and another manufacturer’s ocular steroid. “It’s good to have options,” Dr. Packer said.

Editors’ note: Dr. Sheppard has financial interests with Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Bausch & Lomb (Rochester, N.Y.), and Vistakon (Pharmaceuticals, Jacksonville, Fla.). Dr. Mah has financial interests with Alcon, Allergan, InSite (Vision, Alameda, Calif.), and Vistakon. Dr. Packer has financial interests with Allergan and Bausch & Lomb.

Contact information

Mah: 412-647-2211,
Packer: 541-687-2110,
Sheppard: 757-622-2200,

Fluroquinolones, new and old … Fluroquinolones, new and old …
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