Abstract
Abstract: :
Purpose: ISV-401 is an ophthalmic formulation containing a long-acting, broad-spectrum semi-synthetic antimicrobial agent and that has been used in various systemic conditions such as respiratory tract infections. In the present study, we evaluate the efficacy of 1% ISV-401 in a S. aureus keratitis model in rabbits. Methods: New Zealand white rabbits were dosed topically with 1% ISV-401 in one eye and control vehicle in the other eye for 5 days: twice on Day 1 and once daily on Days 2-5. Twenty-four hours after the last dose, corneas were intrastromally injected with colony forming units (cfu) of S. aureus. Eyes were graded in masked fashion for keratitis severity at 6, 12, 24, and 48 hours following inoculation. Corneas were harvested for quantitation of viable bacteria from animals euthanized at either 6 or 48 hours post-inoculation. Results: At 48 hours, 1% ISV-401 significantly reduced the keratitis severity scores (ISV-401, 0.50 0.84 [mean SD] vs. controls, 19.7 2.73; p<0.005) and the colony forming units (cfu) per cornea (ISV-401, 2.67 6.53 x 100 vs. control, 1.69 3.97 x 107; p<0.005). Conclusion: This study suggests that 1% ISV-401 is a long-acting ophthalmic antimicrobial formulation. Application of the formulation as infrequently as once daily was highly effective in preventing the development of S.aureus keratitis.
Keywords: 316 animal model • 319 antibiotics/antifungals/antiparasitics • 390 drug toxicity/drug effects