Fourth-generation fluoroquinolone widens the choice of antibiotic

September 15, 2009

The introduction of a new fourth-generation fluoroquinolone for ophthalmic use may prompt an assessment of the pros and cons of the available agents. James P. McCulley, MD, explains his continued preference for moxifloxacin 0.5% (Vigamox, Alcon).

Key Points

Dallas-The recent introduction of besifloxacin ophthalmic suspension 0.6% (Besivance, Bausch & Lomb) may cause ophthalmologists to wonder about the role of this new fourth-generation fluoroquinolone in clinical practice.

"The availability of besifloxacin is a welcome addition, but it does not challenge my current preference for moxifloxacin," said Dr. McCulley, professor and The David Bruton Jr. Chair in Ophthalmology, University of Texas Southwestern Medical School, Dallas. "Comparing the fourth-generation fluoroquinolones, I see no remarkable differences in potency, while moxifloxacin appears to offer the best bioavailability, and there are some formulation issues with besifloxacin that may be associated with safety concerns.

Efficacy issues

Dr. McCulley said that superior penetration into the cornea and aqueous humor is the primary reason why he favors moxifloxacin, considering that the efficacy of any antibiotic is determined by both MIC values and the ability of the medication to reach the target site at an appropriate concentration. Information from in vitro antimicrobial testing indicates that while there may be some differences in potency between the three fourth-generation fluoroquinolones considering specific organisms, they are probably not clinically significant taking into account concentrations achieved in vivo, and no one agent emerges as providing greater broad-spectrum activity.

However, based on available data, moxifloxacin clearly offers superior bioavailability among the fourth-generation fluoroquinolones. Moxifloxacin penetrates the cornea faster and better than gatifloxacin or besifloxacin to reach a concentration in the anterior chamber that exceeds that achieved with the other two products.

"Resistance of some bacteria is an issue for each of the fourth-generation fluoroquinolones, but in general, all three offer potent broad-spectrum activity. The advantage of moxifloxacin is that it achieves very high concentrations in the key ocular tissues," Dr. McCulley said.

"Results from studies performed by me and other investigators show that moxifloxacin reaches concentrations in the aqueous humor that are 10-fold higher than the MIC of common ocular pathogens and that exceed the minimum bactericidal concentrations and mutant prevention concentrations as well," he added. "Comparative studies show there is better penetration with moxifloxacin than gatifloxacin, and while there are few reports on besifloxacin pharmacokinetics, the available data suggest it does not penetrate as well as moxifloxacin."

Toxicity issues

Dr. McCulley said that potential concerns about the safety of besifloxacin give him reason to avoid switching from moxifloxacin to besifloxacin. Not only does the commercially available formulation of besifloxacin contain the highest concentration of active ingredient within the category of fourth-generation fluoroquinolones-0.6% besifloxacin versus 0.5% moxifloxacin and 0.3% gatifloxacin-but it also has the highest concentration of benzalkonium chloride (BAK). Besifloxacin is formulated with 0.010% BAK while gatifloxacin contains 0.005% BAK and moxifloxacin is self-preserved.

"When gatifloxacin first became available, I was concerned about the potential for BAK-related corneal toxicity," Dr. McCulley said. "That problem has not emerged as a clinically important issue. However, the fact that [the besifloxacin formulation] contains a higher concentration of fluoroquinolone relative to the other products in this class combined with a higher concentration of BAK gives me cause for concern until more safety data become available."