Vancomycin levels after intravitreal injection. Effects of inflammation and surgery.

Abstract

Vancomycin hydrochloride for intraocular injection is the drug of choice for the treatment of suspected gram-positive endophthalmitis. To study its intraocular pharmacokinetics, we injected vancomycin into the vitreous cavity of phakic, aphakic, and aphakic-vitrectomized rabbit eyes and determined its rate of clearance. Inflamed eyes were compared to control eyes in each group. Three groups of eyes were prepared. The eyes in Group 1 were phakic, the eyes in Group 2 had the lens removed, and the eyes in Group 3 had both the lens and central vitreous removed. Each group was subdivided into a control group and a group made inflamed by injection of heat-killed Staphylococcus epidermidis. Vancomycin hydrochloride 1 mg in 0.1 cc of diluent was injected into the midvitreous cavity and samples obtained at 2 or 3, 8, 24, and 48 hours after injection. Vancomycin concentrations were measured and clearance rates were calculated for each of the groups. Vancomycin was cleared substantially faster from aphakic-vitrectomized eyes (half-life 9.0 hours) and aphakic eyes (half-life 8.9 hours) than phakic eyes (half-life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group. Clearance of vancomycin from the phakic eye is prolonged compared to that of beta-lactam antibiotics, an important pharmacokinetic advantage in treating endophthalmitis. Its clearance from aphakic-vitrectomized eyes is dramatically faster than from phakic eyes and is similar to that of other antimicrobial agents.