A Practical Look At the New Fluoroqinolones
Theoretical risk becomes a real concern with the release of a nonpreserved anti-infective.
By Randall J. Olson, M.D., Salt Lake City

The primary risk of a nonpreserved ocular anti-infective is the potential for contamination. Until recently, this was strictly a theoretical concern because all anti-infectives in multi-drop form were preserved. However, since the release of moxifloxacin ophthalmic solution 0.5% (Vigamox), a nonpreserved the fourth-generation fluoroquinolone, the contamination risk is now a reality.

Because this risk is a new one, we don't yet know whether contamination will be exceedingly rare or fairly common. We know it's bound to occur -- we just don't know how often.

Better spectrum of coverage

Including a preservative in an anti-infective equates to a much broader spectrum of prevention. Of course, the degree of prevention depends on the anti-infective.

For instance, moxifloxacin 0.5% is an effective bacterial anti-infective that passed U.S. Pharmacopoeia preservative efficacy testing for yeast and fungus; yet it has no effect on virus. A chemical disinfectant, on the other hand, would have at least some effect on all the microbial contaminants.

The preservative most commonly used, benzalkonium chloride (BAK), even at very low levels, does more than the moniker "preservative" implies. It doesn't just preserve, and it doesn't just extend the drug's shelf life; it's also an anti-infective in its own right.

An eye that's getting an antibiotic is usually compromised in some way. We often use antibiotics in conditions where even the possibility of infection is a concern. But if you have an eye that's already susceptible to infection, the last thing you want to do is introduce a contaminant that resists your powerful fourth-generation fluoroquinolone. That would be a disaster.

At this point, resistance doesn't seem to be much of an issue with the fourth-generation fluoroquinolones, so risk of contamination doesn't seem too great. But we mustn't forget that, with time, all agents do have holes in their protection.

Solving a nonexistent problem?

How practical is the concern about toxicity from anti-infective formulations with BAK? What difference does it make with respect to patients?

Studies are springing up in response to those questions. One is underway at the John A. Moran Eye Center at the University of Utah School of Medicine. We want to determine whether the absence of preservative in an ocular anti-infective has a practical impact on the patient. Any really useful study would take into account the abuse these bottles of drops are exposed to in realistic situations, and consider that a significant risk factor.

Another relevant question is: Why be preservative-free? The only possible answer is concern about epithelial toxicity. We're all concerned about epithelial toxicity, and anything we can do to reduce its risk is a plus. However, we don't have any evidence supporting the theory that nonpreserved moxifloxacin 0.5% is less toxic than a preserved solution.

In fact, it appears that the other recently released fourth-generation fluoroquinolone, gatifloxacin ophthalmic solution 0.3% (Zymar), which is preserved with 0.005% BAK, may be less irritating to the epithelium. Being preservative-free seems to be a solution to a problem that never really existed for the vast majority of patients.

Dr. Olson is professor and chair of Ophthalmology at the University of Utah School of Medicine and director of the John A. Moran Eye Center for Cornea and External Eye Diseases.