Purpose: To investigate the penetration of cefepime (a fourth-generation cephalosporin) into the vitreous after single-dose intravenous administration to human subjects. Methods: Thirty phakic patients about to undergo vitreous surgery received 1 g (group 1, 15 patients) or 2 g cefepime (group 2, 15 patients) in a single intravenous injection before surgery. The indications for vitreous surgery were retinal detachment with proliferative vitreoretinopathy (24 patients), retinal detachment associated with giant retinal tear (4 patients), macular hole (1 patient) and intraocular foreign body (1 patient). Samples of vitreous and serum were obtained at 0.5, 1, 2, 4 and 12 h after injection. Three patients were used for each sampling time and for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high-performance liquid chromatography (HPLC). Results: All the patients had detectable cefepime in their vitreous and serum measurable by HPLC. The level of cefepime in the vitreous peaked at 2 h and reached a minimum at 12 h after intravenous injection in both groups. A mean peak vitreous level of cefepime was 1.91 +/- 0.13 mug/ml in group 1 and 2.86 +/- 0.37 mug/ml in group 2. The level of cefepime in the vitreous at 12 h after injection was 0.89 +/- 0.14 mug/ml in group 1 and 0.97 +/- 0.30 mug/ml in group 2. Conclusion: The vitreous level of cefepime after intravenous injection was below the minimum inhibitory concentration (MIC90) against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, bit was over the MIC90 against Proteus mirabilis, Klebsiella spp., Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes and Enterobacter spp. Copyright (C) 2002 S. Karger AG, Basel.