Abstract
Purpose::
To compare the efficacy of ZYMAR® (0.3% gatifloxacin [GAT]) and vancomycin [VAN] and to evaluate the possible therapeutic value of the preservative 0.005% benzalkonium chloride [BAK] in ZYMAR®, in the GAT-resistant, methicillin-resistant Staphylococcus epidermidis (GR-MRSE) NZW rabbit keratitis model.
Methods::
In the Study 1, 12 rabbits each, in 2 experiments, were inoculated intrastromally in both eyes with 1000 cfu of a GR-MRSE ocular isolate. The rabbits were divided into 3 treatment groups of 3 rabbits each per exp.: I - ZYMAR® (0.3% GAT) (Allergan Inc., Irvine CA); II -fortified VAN 50 mg/ml; III - saline (Control). In Study 2, 15 rabbits each in 2 experiments were similarly inoculated with the same GR-MRSE isolate. The rabbits were divided into 4 treatment groups of 3 rabbits each per exp.: I - ZYMAR® (0.3% GAT + 0.005% BAK); II - 0.005% BAK; III - 0.3% GAT (ZYMAR® without 0.005% BAK); IV - saline (Control). For both experiments, at 4 hours PI, topical treatment was initiated in both eyes every 15 minutes for 5 hours (21 total doses). One hour after therapy, the corneas were homogenized for viable bacterial counts. In addition, 6 rabbits were sacrificed 4 hours PI to determine the colony counts at the onset of therapy (ONSET) in both experiments. The colony counts from both eyes were averaged, Log10 converted, and analyzed using ANOVA.
Results::
Study 1, Exp. 1 - Both ZYMAR® (3.1 ± 0.8 [mean ± standard deviation] Log10 cfu/ml) and VAN (2.8 ± 1.1) had significantly fewer colony counts compared with ONSET (5.1 ± 0.1) and Control (7.5 ± 0.03) (p<0.001). Exp 2. demonstrated similar results: ZYMAR® (3.1 ± 1.4), VAN (3.8 ± 1.0), ONSET (5.3 ± 0.1), Control (7.5 ± 0.3) (p=0.001). Study 2, Exp. 1 - ZYMAR® (1.8 ± 0.8) and GAT (2.3 ± 0.8) demonstrated significantly fewer colony counts compared with ONSET (5.0 ± 0.3), BAK (8.7 ± 0.3), and Control (7.4 ± 0.2) (p<0.001). Exp. 2 demonstrated similar results: ZYMAR® (1.0 ± 0.5), GAT (1.1 ± 0.2), ONSET (4.5 ± 0.1), BAK (7.7 ± 0.4), Control (8.5 ± 0.2) (p<0.001).
Conclusions::
ZYMAR® and VAN were very effective in reducing the number of GR-MRSE colony counts in the NZW rabbit keratitis model. BAK had no effect on the efficacy of GAT in this model. Therefore, 0.3% GAT is effective alone and does not need 0.005% BAK in the treatment of a GR-MRSE infection in the NZW rabbit keratitis model.
Keywords: antibiotics/antifungals/antiparasitics • keratitis • drug toxicity/drug effects