Intraocular Penetration of Oral Linezolid in Humans

Abstract

Abstract: : Purpose: Linezolid is a synthetic antibiotic of the oxazolidinone class. It has inhibitory activity against gram-positive bacteria including methicillin resistant Staphylococcus aureus, vancomycin resistant enterococci (VRE), and penicillin resistant Streptococcus pneumoniae. Linezolid also exhibits activity against some anaerobes including Propionbacterium acnes, Peptostreptococcus spp. Bacteroides fragilis, C. difficile, and C. perfringens. We wished to study if the oral 600mg tablet could produce inhibitory levels in the aqueous and vitreous humor after one or two tablets.Methods: Patients 18 years of age or older undergoing primary vitrectomy surgery were given either one tablet or 2 tablets (12 hours apart) anywhere from 1 to 4 hours prior to surgery. Prior to any surgical procedure, aqueous, vitreous and blood samples were obtained from the patient. The aqueous and vitreous samples were placed on ice and then frozen. The blood was centrifuged and the serum collected and frozen for future analysis along with the aqueous and vitreous.Results:13 patients receiving 1 tablet of linezolid had aqueous and vitreous fluids were sampled less than 2 hours after administration. Aqueous, vitreous and serum averaged 0.77 + 0.6 mcg/ml, 0.3+ 0.3mcg/ml and 5.0+ 3.25 mcg/ml respectively. 9 patients had aqueous, vitreous and serum samples obtained more than 2 hours (mean 214 minutes + 64) after one tablet administration with resulting concentrations of 3.8 + 1.2, 2.31 + 1.4 and 7.6 + 2.7 mcg/ml, respectively. 7 patients were administered 2 tablets, 12 hours apart (sample obtained mean time of 351 + 232 minutes) and obtained aqueous, vitreous, and serum concentrations of 6.6 + 2.7mcg/ml, 5.7 + 2.7 mcg/ml and 10.3 + 4.1mcg/ml. Ocular fluids exhibited mean inhibitory levels against all gram-positive bacteria including VRE, MRSA and Streptococcus pneumoniae. Conclusions: Oral linezolid 600mg q 12 hours x 2 doses provided mean inhibitory levels in the aqueous and vitreous fluids against major gram-positive bacteria including VRE, MRSA and Streptococcal species.

Keywords: antibiotics/antifungals/antiparasitics • endophthalmitis • drug toxicity/drug effects