Clearance of intravitreal daptomycin in uveitis-induced rabbit model

To investigate the elimination rate of daptomycin after intravitreal injection in uveitis-induced rabbits.

Intravitreal injection of the single dose of 200 μg/0.05 mL daptomycin was administered to rabbits starting 24 h after induction of uveitis by an intravitreal endotoxin injection. Aqueous humor and vitreous humor samples of eight eyes per time point were collected at selected time intervals (1, 3, 6, 24, 48, 72 and 96 h), and the in vitreous half-life was calculated. Daptomycin concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography.

The vitreous concentration was noted to decline slowly with time. The mean vitreous concentration was 23.25 ± 10.99 μg/mL and 11.10 ± 3.33 μg/mL at 96 h in inflamed and normal eyes, respectively. The vitreous daptomycin concentration showed an exponential decay with a half-life of 25.67 h in normal eyes and 34.6 h in inflamed eyes. The aqueous levels of daptomycin in normal eyes were low but remained significantly higher than those of inflamed eyes.

Given that the injected dose corresponds to several times the minimum inhibitory concentrations of organisms most involved in endophthalmitis, and that therapeutic levels are present up to 96 h after injection, intravitreal daptomycin should be considered for the treatment of endophthalmitis caused by Gram-positive bacteria.