Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration*1

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 113, 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 mug/mL, 0.3+/-0.3 mug/mL, and 5.0+/-3.3 mug/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 mug/mL, 2.3+/-1.4 mug/mL, and 7.6+/-2.7 mug/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 mug/mL, 5.7+/-2.7 mug/mL, and 10.3+/-4.1 mug/mL, respectively. Conclusions: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC90) 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 MIC90 were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours. (C) 2004 by the American Academy of Ophthalmology.