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

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 μg/mL, 0.3±0.3 μg/mL, and 5.0±3.3 μg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8±1.2 μg/mL, 2.3±1.4 μg/mL, and 7.6±2.7 μg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6±2.7 μg/mL, 5.7±2.7 μg/mL, and 10.3±4.1 μg/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.