Ocular penetration of topically applied 1% daptomycin in a rabbit model

To evaluate the ocular penetration of daptomycin, a new antibiotic agent targeted against Gram-positive organisms.

Thirty-two New Zealand white rabbits were divided into 4 equal groups. One drop of 50 μL 1% daptomycin was administered to group 1. In group 2, 1 drop of 1% daptomycin was administered after the corneal epithelium was scraped. In group 3, 1 drop of 1% daptomycin was administered every 15 min for 1 h (keratitis protocol). In group 4, the keratitis protocol was applied after the corneal epithelium was scraped. In groups 1 and 2, aqueous humor samples were collected 30 min, 1 h, and 2 h after the single drop under general anesthesia. All the animals in groups 3 and 4 were humanely killed. Cornea, aqueous humor, and vitreous samples were collected 1 and 2 h after the last drop. Daptomycin concentrations were measured by high-performance liquid chromatography.

Each group comprised 8 rabbits. Daptomycin was not detected in the aqueous humor in groups 1 and 2. In group 3, the mean values at 1 h in the aqueous humor and cornea, respectively, were 1.90±0.15 μg/mL and 3.93±0.67 μg/g, and at 2 h were 1.71±0.42 μg/mL and 4.13±0.46 μg/g. In group 4, the mean values at 1 h were 5.19±0.50 μg/mL and 7.10±0.35 μg/g, and at 2 h were 4.96±0.47 μg/mL and 7.22±0.34 μg/g. Daptomycin was not detected in vitreous samples in groups 3 and 4.

Single-drop administration does not yield a detectable daptomycin concentration in aqueous humor in neither nonscraped nor scraped group. In the multiple-drop regimen, daptomycin seems to penetrate well into the aqueous humor and cornea both in nonscraped and scraped groups. However, this concentration may not cover the minimum inhibitory concentration (MIC) of organisms such as Enterococcus fecalis.