Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration.

Author(s): Fiscella RG, Lai WW, Buerk B, Khan M, Rodvold KA, Pulido JS, Labib S, Shapiro MJ, Blair NP

Affiliation(s): Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.

Publication date & source: 2004-06, Ophthalmology., 111(6):1191-5.

Publication type: Clinical Trial; Randomized Controlled Trial

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.