Ocular penetration of subconjunctival oxacillin, methicillin, and cefazolin in rabbits with staphylococcal endophthalmitis.

The concentrations of oxacillin, methicillin, and cefazolin were examined in the infected eyes of pigmented rabbits with Staphylococcus aureus endophthalmitis after a subconjunctival dose of 100 mg. The three drugs had fairly similar ocular pharmacokinetics. The tissue concentration usually peaked within 30 min. Levels in the aqueous humor rose more slowly; the respective maximal concentrations of methicillin, oxacillin, and cefazolin were 72, 1,180, and 111 micrograms/ml. Oxacillin also produced the highest levels in the cornea. Penetration of the vitreous humor was poor with all three drugs, apparently owing to a diffusional barrier in the choroid-retina tissue complex. The respective median vitreous levels of methicillin, oxacillin, and cefazolin were 0.7, 0.6, and less than 0.8 micrograms/ml. These values are close to the concentrations usually required to inhibit S. aureus in vitro. Our results suggest that subconjunctival oxacillin achieves higher concentrations in anterior ocular tissues than do the other two drugs, but more aggressive approaches are necessary in treating endophthalmitis.