Ocular penetration of topically applied linezolid in a rabbit model.

PURPOSE

To evaluate ocular penetration of topically applied linezolid, a new antibiotic agent targeted against gram-positive organisms.

SETTING

Laboratory of Pharmacology, University Hospital of Strasbourg, Strasbourg, France.

METHODS

New Zealand White rabbits were divided into 3 equal groups. One drop of 50 microL (2 mg/mL) linezolid was administrated in Group 1. In Group 2, eyes were dosed in accordance with a keratitis protocol (1 drop of 2 mg/mL every 15 minutes for 1 hour). Aqueous humor was sampled 6 times from immediately after to 3 hours after drop delivery. In Group 3, a keratitis protocol was implemented before the animals were humanely killed. Conjunctiva, cornea, vitreous, and blood samples were collected 1 hour and 2 hours after the last drop. Linezolid concentrations were measured by high-performance liquid chromatography.

RESULTS

Each group comprised 8 rabbits. In Group 1 and Group 2, the peak linezolid concentration in the aqueous humor (mean 0.87 mg/L +/- 0.16 [SD] and 2.17 +/- 0.4 mg/L, respectively) was 45 minutes after the last drop delivery. In Group 3, the concentrations 1 hour and 2 hours after the last drop were higher than 3 microg/g in the conjunctiva samples and higher than 4 microg/g in the cornea samples. The linezolid concentration in the vitreous and serum was negligible.

CONCLUSIONS

Linezolid levels in the aqueous humor, conjunctiva, and cornea exceeded the minimum inhibitory concentration of most gram-positive organisms that cause bacterial keratitis and endophthalmitis. Linezolid could be a valuable alternative in cases of increased resistance to vancomycin.