Oxacillin for bacterial endophthalmitis: subconjunctival, intravenous, both, or neither?

We compared the intraocular concentrations of oxacillin given by continuous intravenous infusion, subconjunctival injection, or combined therapy in a rabbit model of Staphylococcus aureus endophthalmitis. At equilibrium during intravenous infusion, concentrations in the aqueous humor, cornea, and choroid-retina were 25% to 30% of the serum level; in contrast, vitreous levels were only 2% of the serum concentration. Subconjunctival injection produced extremely high levels in the cornea and aqueous and moderate concentrations in the choroid-retina; vitreous penetration remained poor (<1 microgram/ml). Combined therapy offered little advantage in terms of concentrations in the aqueous or cornea and had a modest effect on levels in the choroid-retina. Vitreous concentrations showed a striking relation to serum levels with all regimens, including subconjunctival ones; although this could have been fortuitous, it suggests an important role for the hematogenous route in this model. Only those modes of delivery producing serum concentrations greater than 50 micrograms/ml consistently resulted in vitreous levels greater than 0.4 microgram/ml. The optimal therapy of bacterial endophthalmitis may require direct intravitreal injection of antibiotic.