Rx Perspectives

Besivance: Potency and Persistence

By Jack Persico, Executive Editor

The arrival of a new pharmaceutical agent is always welcome by clinicians, but perhaps even more so in ocular antibiotics, given the urgent need to combat resistant organisms.

Besiflox acin, a new fluoroquinolone (FQ) marketed as Besivance by Bausch+Lomb, shares with other recent FQs a binding af fin ity for both enzymes at work in bacterial synthesis: DNA gyrase and DNA topoisomerase IV. This thwarts development of resistance by requiring two mutations for the organism to achieve resistance; older FQs targeted just one or the other enzyme. And the inclusion of a chloride group, unique to Besivance, allows it to achieve a more balanced targeting of these two enzymes, notes Bascom Palmer corneal specialist Terry O'Brien, MD. Its 0.6% concentration gives it added potency as well.

The drug uses a muco adhesive vehicle called Durasite that helps increase solubility, Dr. O'Brien says, and extends its contact time on the ocular surface to five hours. This produces "exceptional tear and tissue levels, far exceeding those of other available FQs," says John D. Sheppard, MD, of Eastern Virginia Medical School. Its levels exceed the MICs of targeted organisms by "several log orders after administration," he says, "and in most cases comfortably exceed the MICs at 24 hours following administration of a single drop."

Clinical Applications

Dr. Sheppard says Besivance is equally or more active than other fourth-generation FQs for all relevant resistant organisms, both gram negative and gram positive, especially methicillin resistant and/or ciprofloxacin-resistant Staph epi and aureus.

Though the drug is indicated for conjunctivitis, Long Island's Marguerite McDonald, MD, says it's appropriate to use modern FQs like Besivance for routine prophylaxis in the perioperative period after cataract surgery "because of the excellent broad spectrum coverage that this class offers."

Dr. Sheppard agrees. "The rising tide of methicillin resistance coupled with a de facto collegial standard protocol demanding a topical FQ for surgical prophylaxis makes besifloxacin my perioperative drug of choice."

Cataract patients and particularly their caregivers are delighted with a BID peri-operative schedule, says Dr. Sheppard. "The mildly viscous vehicle allows better reliability in coating the ocular surface with one drop, since so many times FQ solutions seem to bounce off the lashes or the cornea in less than cooperative patients." It is easy to see the Durasite "smile" along the lower lid as Besivance fills the inferior cul de sac in accomplishing complete surface distribution, he says.

A single 5-cc bottle is sufficient for a two-week prophylaxis regimen. "Patients, caregivers, family members, and especially ASC or OR staff need to be reminded not to waste drops," Dr. Sheppard says. "One drop in the eye, for sure, is all that is needed to provide adequate therapeutic effect: a second simultaneous drop is totally wasted, down the cheek."

Corneal ulcer management with Besivance may require less of a loading dose (e.g., every 10 minutes for 1-2 hours rather than every five minutes), perhaps because of the Durasite vehicle, says Paul Karpecki, OD, a cornea and ocular surface disease expert from Lexington, KY. "In treating 30+ corneal ulcers with Besivance, I feel the response on day one has far surpassed my experience with previous medications," he says. He adds that its on-label use for conjunctivitis is patient-friendly. "Because its dosing is TID every 4-12 hours, it is especially helpful in pediatric conjunctivitis where the child can be dosed in the morning, after school and before bed."

Though some clinicians may be loath to routinely use a new agent due to eventual resistance, experts say it's inevitable. "All Staph infections may be methicillin resistant within 10 years, much as all Streptococcus species became penicillin resistant by the 1960s," says Dr. Sheppard.

"All antibiotics eventually fall prey to increasing resistance," observes Dr. McDonald, "but Besivance has a major ‘head start’ because it has never been used systemically."

In one in vitro study involving rabbit eyes, Besivance was shown to have an eight-fold lower MIC₉₀ against MRSA than other fourth-gen FQs, says Dr. Karpecki. This is at least partly due to the absence of a systemic version of Besivance, he says.

Most resistance occurs not from medical use but primarily from agricultural use, Dr. Karpecki says, as antibiotics are placed in livestock feed to allow the animals to grow larger.

Highly resistant strains such as MRSA and MRSE are some of the most common pathogens following surgical procedures, Dr. Karpecki says, and thus prophylactic use of Besivance would be prudent. "I believe that using the most potent and broadest spectrum antibiotic will do more to prevent resistant strains than using a less potent antibiotic, especially in light of the trend toward increasingly resistant bacteria." OM