Why a Preservative is Beneficial to the Formulation of Zymar
A Discussion on the Pros and Cons.
BY Y. RALPH CHU, M.D. AND JESSICA C. MATSUMOTO, O.D.

A key issue concerning the use of Zymar (gatifloxacin ophthalmic solution, Allergan) has been its incorporation of the preservative benzalkonium chloride 0.005% (BAK). This preservative has been used historically in many ophthalmic formulations such as, glaucoma medications and contact lens solutions. Preservatives like BAK have bacteriostatic properties in the bottle; they prevent drug decomposition and aid in the penetration of the drug into the ocular tissues. Including BAK in the solution enhances the speed at which gatifloxacin eradicates microbes. It has been established that higher concentrations of BAK with prolonged dosing carries a risk of increased cytotoxicity and increased surface dryness; however, when dosed on a routine regimen, these side effects are low to rare. The lower concentration of BAK in Zymar provides an advantage to the practitioner and patient.

Gatifloxacin and BAK hasten microbial eradication, as opposed to gatifloxacin alone. A recent study conducted by Blondeau and colleagues1 investigated the antimicrobial efficacy of gatifloxacin with and without BAK. In this study, it was found that gatifloxacin with BAK provided greater antimicrobial efficacy than gatifloxacin without BAK. More specifically, the combination resulted in lower minimal inhibitory concentration (MIC) of both control strains and clinically ocular bacterial pathogens. The investigation found that BAK has an additive effect when used with gatifloxacin in reducing bacterial MIC's; its synergistic effects with gatifloxacin allow increased antimicrobial efficacy because BAK protects the ocular tissues from infections likely caused by inadvertent bottle contamination.

A similar study by Eser and colleagues2 compared antimicrobial activity of gatifloxacin with BAK against nonpreservative moxifloxacin 0.5% in strains of Staphylococcus aureus and Staphylococcus epidermidis. It was found that after
15 minutes of instilling gatifloxacin with BAK, there was complete eradication on all tested strains. However, after
15 minutes of instilling nonpreserved moxifloxacin, all tested strains were not fully eradicated. Although the concentration of nonpreserved moxifloxacin is higher, microbial kill time was slower than that of the gatifloxacin with BAK. This demonstrates that BAK may act synergistically with gatifloxacin to provide an improved microbial effect. The faster kill rate of gatifloxacin and BAK suggest that it is effective in maintaining an aseptic ocular surface postoperatively.

Additionally, the spectrum that BAK covers expands beyond bacteria. Filamentous fungi and yeasts, such as Candida, can contaminate the bottles of ophthalmic preparations that may cause infections such as endophthalmitis. The surfactant effects of BAK disrupt cell membrane permeability and lead to cellular lysis in bacteria and fungi. In a similar study to Eser and colleagues,2 gatifloxacin with BAK was compared to nonpreserved moxifloxacin 0.5% in their activity against 20 strands of yeast isolates. It was found that gatifloxacin with BAK was more effective at eradicating all strains of yeast and filamentous fungi tested than moxifloxacin 0.5%.

For these reasons, gatifloxacin preserved with BAK is more efficient than nonpreserved gatifloxacin and nonpreserved moxifloxacin. When dosed on a short-term regimen and used properly, the properties preservatives such as BAK provide can create more benefit than harm for the patient. Allergan's formulation of gatifloxacin with BAK is designed to eradicate bacteria quickly.