2003 OMIG, Abstract 3

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The Successful Treatment of Gatifloxacin-Resistant Staphylococcus aureus Keratitis with Gatifloxacin (Zymar™) in a NZW Rabbit Model
FS Mah, EG Romanowski, KA Yates, RP Kowalski, YJ Gordon.
The Charles T. Campbell Lab, University of Pittsburgh

Purpose: It is generally believed that in vitro resistance does not always correlate with in vivo efficacy in topical ocular therapy. In this study, we determined whether gatifloxacin-resistant S. aureus (Gat-R-Sa) keratitis could be successfully treated with topical 0.3% gatifloxacin (GAT) (Zymar™) in an animal model.
Methods: Two clinical isolates of Gat-R-Sa, with MICs of 12 and 64ug/ml to gatifloxacin, were used in separate experiments. Each consisted of 4 treatment groups of 6 animals (GAT, 0.5% levofloxacin [Quixin™], 0.3% ciprofloxacin [Ciloxan™], and Saline) and a baseline (onset of therapy) colony count control group. Rabbits were infected intrastromally with 2 X 103cfu in both eyes. Topical therapy began 4 hours PI every 15 minutes for 5 hours (21 doses). After therapy, the eyes were graded for clinical signs of infection. Subsequently, the corneas were homogenized to determine a viable bacterial count. The clinical and the colony count data were analyzed with non-parametric and continuous statistical methods.
Results: In the treatment of Gat-R-Sa (MIC of 12ug/ml), GAT demonstrated a significantly lower clinical corneal infiltrate score compared with all other groups and demonstrated a bactericidal 3.8-log decrease in colony counts compared with the baseline colony count and a 5.9-log decrease in colony counts compared with the Saline control. For Gat-R-Sa (MIC of 64ug/ml), GAT demonstrated significantly lower overall ocular scores compared with all other groups and demonstrated a 2.7 log decrease in colony counts compared with the baseline colony count and a 5.1-log decrease in colony counts compared with the Saline control. For both isolates, GAT demonstrated a significantly greater decrease in colony counts compared to all other treatment groups.
Conclusion: We demonstrated “Proof of Principle” that in vitro antibiotic resistance does not always correlate with in vivo antibiotic resistance. An aggressive treatment regimen with GAT appears to overcome in vitro resistance resulting in the successful treatment of Gat-R-Sa infection in the NZW rabbit keratitis model.

Disclosure: This study was supported by a grant from Allergan, Inc. (Irvine, CA)

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