Aqueous and Vitreous Penetration of Linezolid and Levofloxacin After Oral Administration

Purpose: To evaluate the time course of drug concentrations achieved in aqueous (AQ), vitreous (V), and serum (S) compartments after oral administration of linezolid and levofloxacin. Design: Randomized, clinical trial. Methods: Settings: Clinical practice. Patient population: Sixteen patients (16 eyes) undergoing vitrectomy who had not had a prior pars plana vitrectomy in the study eye were randomly assigned to one of 4 groups. Intervention: AQ, V, and S samples were obtained from all subjects after single concomitant doses of linezolid 600mg and levofloxacin 750mg between 1 and 12 h before the procedure: group A - 1-3 h; group B - 3-6 h; group C - 6-9 h; group D - 9-12 h. Main outcome measures: AQ, V, and S concentrations of linezolid and levofloxacin. Results: Overall mean concentrations +/- standard deviation (mu g/mL) achieved by linezolid in AQ, V, and S compartments were 3.32 +/- 2.06, 2.98 +/- 1.87, and 7.91 +/- 3.94, respectively. Overall mean concentrations +/- standard deviation (mu g/mL) achieved by levofloxacin in AQ, V, and S compartments were 2.19 +/- 1.92, 1.95 +/- 1.27, and 7.38 +/- 3.47, respectively. Conclusions: Single concomitant doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentration for 90% of common ocular gram-positive and gram-negative pathogens up to 12 h after administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of endophthalmitis.