Preservative enhances antimicrobial activity of gatifloxacin

Fort Lauderdale, FL-The preservative benzalkonium chloride (BAK) significantly enhances the antimicrobial activity of gatifloxacin against methicillin-and fluoroquinolone-resistant Staphylococcus aureus, according to the results of in vitro susceptibility testing and a study using an established animal model of experimentally induced keratitis.

The research was presented at the annual meeting of the Association for Research in Vision and Ophthalmology.

"In vitro susceptibility testing is conducted using the antimicrobial agent only and not with the commercially available preparation," said Dr. Blondeau, chairman of clinical microbiology, Royal University Hospital and University of Saskatchewan, Saskatoon. "However, BAK is a membrane active agent, and there has been information suggesting that by itself, BAK has antimicrobial properties.

"Since the commercially available ophthalmic solution of gatifloxacin contains BAK and moxifloxacin is unpreserved, the observations in our study may have important clinical implications for selecting a topical ophthalmic antibiotic solution," Dr. Blondeau continued. "In light of reports that the incidence of moxifloxacin-and gatifloxacin-resistant MRSA is on the rise, our findings that gatifloxacin plus BAK has enhanced potency against these multidrug-resistant strains are of particular interest."

For the 67 isolates tested, MIC values ranged from ≤0.008 to 0.125 μg/ml for gatifloxacin plus BAK, but were between 0.0063 and 8 μg/ml for gatifloxacin and ranged from ≤0.016 to 16.0 μg/ml for moxifloxacin. For the 35 gatifloxacin-resistant MRSA isolates, gatifloxacin MIC values ranged from 4 to 16 μg/ml. The MIC values for gatifloxacin plus BAK were between <0.008 and 0.125 μg/ml and ranged from 1 to 16 μg/ml for moxifloxacin; for 12 (34%) of the isolates, the moxifloxacin MIC value was ≤2 μg/ml.

Rabbit model

Francis S. Mah, MD, and colleagues at the University of Pittsburgh used the New Zealand white rabbit keratitis model to investigate the effect of BAK on the antibacterial activity of gatifloxacin. Twenty-four animals were given an intrastromal inoculation with 3 × 105 CFU of a methicillin-and fluoroquinolone-resistant strain of S aureus and 4 hours later were divided into four treatment groups to receive the commercially available preparation of gatifloxacin ophthalmic solution (Zymar), 0.3% gatifloxacin in complete vehicle without 0.005% BAK, 0.005% BAK (Zymar vehicle without gatifloxacin), or saline. Each eye was treated with 21 doses administered at 15-minute intervals over 5 hours.

After the last dose, the animals were evaluated at the slit lamp for signs of infection and were euthanized within 1 hour to harvest the corneas for determination of viable bacterial count. The results of those assessments showed gatifloxacin both with and without BAK significantly reduced the clinical signs of infection and fluoroquinolone-resistant colony counts compared with BAK alone and saline control. There was no difference between the complete commercial preparation and gatifloxacin alone in the clinical evaluation, but the gatifloxacin plus BAK was significantly more effective than gatifloxacin alone in reducing the bacterial colony counts.