Besifloxacin provides broad anti-bacterial coverage

June 1, 2010

Besifloxacin ophthalmic suspension 0.6% provides potent broad-spectrum anti-bacterial coverage coupled with favorable safety, tolerance and dosing convenience.

Loma Linda, CA-Besifloxacin ophthalmic suspension 0.6% (Besivance, Bausch + Lomb) provides potent broad-spectrum anti-bacterial coverage coupled with favorable safety, tolerability, and dosing convenience.

Based on this profile, John C. Affeldt, MD, said he considers besifloxacin his fourth-generation fluoroquinolone of choice. Dr. Affeldt is a fellowship-trained cornea specialist, a member of the full-time attending faculty at Loma Linda University Medical Center, Loma Linda, CA, and assistant clinical professor, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles.

Treatment of corneal infections is an important segment of his practice, and he also uses topical anti-microbial agents frequently as prophylaxis against infection when performing corneal surgery procedures.

"According to their prescribing information, three of the four currently available ophthalmic fourth-generation fluoroquinolones are indicated specifically for the treatment of bacterial conjunctivitis caused by susceptible organisms, although in ophthalmic practice, they are widely used off-label to treat and prevent other infections," he said. "In my opinion, which I think is consistent with [that of] most cornea specialists, the fourth-generation fluoroquinolones represent our current best choice for a monotherapeutic antibacterial agent because of their broad-spectrum activity and gentleness to the ocular surface."

Broader, more potent coverage

"However, relative to gatifloxacin and moxifloxacin, besifloxacin offers broader and more potent anti-infective coverage, especially against gram-positive bacteria, which account for the vast majority of ocular surface infections, and besifloxacin is formulated in a preparation that is particularly well-tolerated and enables a more convenient, less frequent dosing schedule," Dr. Affeldt said.

Concerns about resistance of some important ocular pathogens to the previously available fluoroquinolones are highlighted by data from the Ocular Tracking Resistance in the United States Today (TRUST) [Am J Ophthalmol. 2008;145:951-958]. Even at that time, high-level in vitro MRSA resistance was found to the tested fluoroquinolones, which included ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin. Based on the minimal inhibitory concentration (MIC) data, the authors of that publication concluded there was a need to consider other therapy when MRSA is the likely infectious organism.

Results of recently published laboratory studies [Antimicrob Agents Chemother. 2009;53:3552-3560 and J Antimicrob Chemother. 2010 April 30, Epub] comparing the in vitro activity of besifloxacin, moxifloxacin, gatifloxacin, and several other antibacterial agents showed besifloxacin had lower MIC values (superior activity) against ciprofloxacin-susceptible Staphylococcus aureus and methicillin- and fluoroquinolone-resistant staphylococci, as well as more rapid bactericidal activity, including against some isolates with in vitro resistance to other fluoroquinolones, noted Dr. Affeldt.

"When the newer-generation fluoroquinolones were introduced, I felt comfortable using them as monotherapy to treat serious ocular surface infections, like corneal ulcers," he said. "However, with the emergence of fluoroquinolone-resistant staphylococci and streptococci, I had to take a step back, and [I] began using a dual-therapy regimen again because of concern about pathogens that had outstripped the activity of the fluoroquinolones.

"The MIC data indicate besifloxacin has very potent activity against some of these difficult organisms, even matching that of vancomycin against some strains of methicillin-resistant S aureus," Dr. Affeldt said. "While this is very exciting information, the clinical efficacy of besifloxacin for eradicating these infections has yet to be proven. Nevertheless, in clinical practice where initial therapy is empirically chosen, I consider besifloxacin the best first-line option."

Mucoadhesive polymer

The clinical activity of besifloxacin also is enhanced by its formulation. The mucoadhesive polymer (DuraSite, InSite Vision) used as the vehicle for besifloxacin extends drug residence time on the ocular surface. In addition, the product is preserved with benzalkonium chloride, which has been shown through in vitro studies to enhance the antibacterial activity of other fluoroquinolones.

The mucoadhesive polymer vehicle used in besifloxacin also contributes to the dosing convenience and tolerability of the product. Prolongation of besifloxacin residence time allows for a less frequent administration schedule compared with other ophthalmic anti-infective agents.

"The recommended dosing interval for besifloxacin is three times a day," Dr. Affeldt said. "However, available pharmacokinetic data suggest twice-daily dosing may be adequate, and I often use that regimen, which translates into better compliance that will likely improve therapeutic success."

The mucoadherent polymer also acts as an ocular lubricant, which makes besifloxacin treatment very comfortable and well-tolerated. The safety and tolerability of besifloxacin ophthalmic suspension are supported by data from the vehicle-controlled studies that led to its approval for the treatment of bacterial conjunctivitis and the results of a randomized trial including moxifloxacin 0.5% (Vigamox, Alcon Laboratories) as the comparator agent [Ophthalmology. 2009;116:1615-1623]. In the latter study, both fluoroquinolones were well-tolerated, but the incidence of eye irritation was significantly greater among patients treated with moxifloxacin compared with the besifloxacin group (1.4% versus 0.3%; p = 0.0201).

FYI

John C. Affeldt, MD
E-mail: johnaffeldt@aol.com

Dr. Affeldt is a speaker for Bausch + Lomb.