Abstract
Abstract: :
Purpose: To compare the efficacy of ZymarTM (gatifloxacin 0.3%), CiloxanTM (ciprofloxacin 0.3%) and 1.4% (14 mg/ml) fortified Tobramycin (TOB) in the treatment of experimental Gram–negative bacterial infections of quinolone–susceptible Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the NZW rabbit keratitis model. Methods: In separate but identical duplicate experiments, a total of 30 NZW rabbits were intrastomally inoculated in both eyes with approximately 1,000 cfu/eye in 25 µl. After 16 hours, the rabbits were divided into the 4 treatment groups (n=6 rabbits per group): 1) Gat, 2) Cip, 3) TOB and 4) saline control. One drop was put in both eyes every 15 minutes for 5 doses then, every 30 minutes for 14 doses (19 total over 8:00). Additionally, 6 rabbits were euthanized at 16 hours to determine corneal colony counts at the onset of therapy. One hour after the final dose, animals were euthanized and corneal colony counts determined. The first experiment utilized a clinical isolate of SM (MICs [µg/ml]: Gat 0.125; Cip 0.047; TOB 1.5). The second experiment utilized the clinical isolate of PA (MICs [µg/ml]: Gat 0.125; Cip 0.19; TOB 0.5). Results: In the SM experiment, Gat (0.8 ± 1.3) (mean ± sd Log10 cfu/ml) and Cip (3.2 ± 1.6) significantly decreased the number SM colony counts compared with TOB (7.2 ± 0.6) and the saline control (7.6 ± 0.6) (p = 0.000, power = 1.0). Gat also significantly decreased the number of SM colony counts compared with Cip (p = 0.000, power = 1.0). Gat (–6.4 Logs) and Cip (–4 Logs) decreased colony counts compared with the onset of therapy control, whereas TOB did not. In the PA experiment, Gat (1.8 ± 2.1), Cip (1.7 ± 1.8), and TOB (1.8 ± 1.5) significantly decreased the number of PA colony counts compared with the saline control (5.3 ± 0.8) (p = 0.000, power =0.9999). There were no differences in PA colony counts among Gat, Cip, and TOB. Gat (–1.8 Logs), Cip (–1.9 Logs), and TOB (–1.8 Logs) decreased colony counts compared with the onset of therapy control. Conclusions: Only ZymarTM and CiloxanTM were effective in reducing the number of SM corneal colony counts in the NZW rabbit keratitis model with ZymarTM being significantly more effective than CiloxanTM. In contrast, ZymarTM, CiloxanTM, and TOB were equally effective in reducing the number of PA corneal colony counts in the NZW rabbit keratitis model. Only clinical trials can prove whether ZymarTM is an effective treatment for PA and SM keratitis in patients.
Keywords: antibiotics/antifungals/antiparasitics • microbial pathogenesis: experimental studies • keratitis