Treatment of staphylococcal keratitis includes tobramycin drops at repeated intervals, a prolonged therapy that is disruptive to the patient. To identify a regimen involving less frequent drug application, we compared the efficacy of fortified tobramycin (1.36%) administered by collagen shields or in topical drop form to rabbit corneas intrastromally infected with staphylococci. Eyes were treated with shields hydrated in and supplemented with fortified tobramycin drops (1.36%) applied every 1, 2, 5, or 10 h, from 10 to 20 h postinfection. For topical drop treatment alone, tobramycin was applied following the identical regimen. Untreated corneas contained 10(6) colony forming units. Shields supplemented with tobramycin drops applied every 1, 2, or 5 h sterilized 100% of the corneas. Shields supplemented with tobramycin drops applied at 10 h sterilized 58% of the corneas. Topical delivery of tobramycin every h sterilized all corneas; drops alone applied at longer intervals, such as 2, 5, or 10 h, sterilized 83%, 17%, and 0% of the corneas, respectively. Collagen shield delivery of tobramycin with supplemental topical drops can eradicate staphylococci in this model with less frequent dosing intervals than are required with topical therapy alone.