The Successful Treatment of Gatifloxacin-resistant Staphylococcus aureus Keratitis With Zymar® (Gatifloxacin 0.3%) in a NZW Rabbit Model

Abstract

To determine whether gatifloxacin-resistant S. aureus (Gat-R-Sa) keratitis could be successfully treated with topical Zymar (gatifloxacin 0.3%) in a rabbit model. Experimental animal study. Two separate studies were performed each using two clinical isolates of Gat-R-Sa, with MICs of 12 and 64 mug/ml to gatifloxacin. Study 1 consisted of four treatment groups (Zymar, Quixin [levofloxacin 0.5%], Ciloxan [ciprofloxacin 0.3%], and saline). Study 2 consisted of Zymar, cefazolin 50 mg/ml, vancomycin 50 mg/ml, and saline. Rabbits were infected intrastromally with 2,000 cfu in both eyes. Topical therapy began after four hours, every 15 minutes for 5 hours. After therapy, the eyes were graded for clinical signs of infection (blepharitis, conjunctivitis, iritis, corneal edema, and corneal infiltrates), and the corneas were homogenized to determine viable bacterial counts. Study 1: for both isolates, Zymar-treated eyes demonstrated significantly lower clinical scores compared with Ciloxan and saline, and significantly decreased the number of viable bacteria recovered compared with all groups. Study 2: for both isolates, Zymar and cefazolin demonstrated significantly lower clinical scores compared with vancomycin and saline. Zymar, cefazolin, and vancomycin significantly decreased the number of viable bacteria recovered compared with the saline control. We demonstrated the "Proof of Principle" that in vitro antibiotic resistance, based on CLSI standards, does not always correlate with in vivo treatment failure in the eye. An aggressive treatment regimen with Zymar appears to overcome in vitro resistance, resulting in the successful treatment of Gat-R-Sa infections in the NZW rabbit keratitis model.