Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis.
Treatment of bacterial keratitis requires frequent application of topical antibiotics. We studied the efficacy of a single topical administration of tobramycin incorporated in large multivesicular liposomes and enmeshed in a fibrin sealant on rabbit corneas infected with Pseudomonas aeruginosa. One cornea each of 25 New Zealand albino rabbits was infected with P. aeruginosa. Twenty-four hours later, the animals were randomly divided into five groups of five. Group A received single hourly drops (50 microliters) of fortified tobramycin (14.5 mg/ml, total of 17.4 mg). Group B received a single topical application of 3.5 mg tobramycin, in 0.1 ml multivesicular liposomes, enmeshed in a fibrin sealant with an overlaying bandage contact lens. Group C was treated in the same manner as group B without the addition of fibrin sealant. Groups D and E served as nondrug-treated controls, with group D receiving topical fibrin-enmeshed liposomes devoid of tobramycin and group E receiving hourly topical balanced salt solution (BSS) drops. All animals were killed 24 h after initiation of therapy. Significantly fewer colonies of Pseudomonas were present in corneas of all three treated groups, as compared with the two nondrug-treated control groups (p less than 0.02). There were significantly fewer colonies of Pseudomonas in groups A and B as compared with group C (p less than 0.02). No significant difference was noted between a single administration of topical fibrinen-meshed tobramycin-encapsulated liposomes (group B) and 24 doses of hourly fortified topical tobramycin (group A, p greater than 0.05). Tobramycin-encapsulated megaliposomes may serve as a useful adjunct in treatment of Pseudomonas keratitis.