Abstract
Abstract: :
Purpose: We determined whether gatifloxacin–resistant S. aureus (Gat–R–Sa) keratitis could be successfully treated with topical 0.3% gatifloxacin (GAT) (ZymarTM) in comparison to vancomycin and cefazolin in an animal model. Methods: Two clinical isolates of Gat–R–Sa, with MICs of 12 and 64 µg/ml to gatifloxacin, were used in separate experiments. Each experiment consisted of 4 treatment groups of 6 animals (GAT, vancomycin 50 mg/ml, cefazolin 50 mg/ml, and Saline) and a baseline (onset of therapy) colony count control group. Rabbits were infected intrastromally with 2 X 103 cfu 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, and 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 12 µg/ml) keratitis, the GAT (3.0) and cefazolin (1.75) treatment groups had the lowest overall median clinical scores and both were lower than vancomycin (9.75) and saline (8.75). The log10 colony count decreases (compared to baseline of 4.92) for GAT, cefazolin, and vancomycin were 3.14, 2.66, and 2.54 cfu/ml, respectively, with only GAT demonstrating a bactericidal 3 log decrease. The mean colony counts of the three antibiotics were equivalent and statistically lower than the saline group. For Gat–R–Sa (MIC of 64 µg/ml), the cefazolin (1.2) treatment group presented with the lowest overall median clinical score followed by GAT (4.9) which was lower than vancomycin (10.6) and saline (10.8). The log10 colony count decreases (compared to baseline of 5.17) for GAT, cefazolin, and vancomycin were 2.57, 3.11, and 2.46, respectively, with only cefazolin demonstrating a bactericidal effect. The mean colony counts of the three antibiotics were equivalent and statistically lower than the saline group. Conclusion:An aggressive treatment regimen with GAT appears to overcome in vitro resistance that results in reducing the bacterial load and clinical signs of Gat–R–Sa infection in the rabbit keratitis model in comparison to cefazolin and vancomycin. Within the framework of the study, GAT therapy was better than vancomycin or cefazolin for treating an isolate with low gatifloxacin resistance (12 µg/ml) whereas the isolate with high resistance (64 µg/ml) appeared to respond better to cefazolin.
Keywords: antibiotics/antifungals/antiparasitics • keratitis • Staphylococcus