AnIn VitroAnalysis of Cephalosporin Corneal Epithellal Toxicity

Using an in vitro rabbit corneal epithelial model, we measured the cytotoxicity and antibacterial efficacy of three cephalosporin antibiotics: cefazolin, cefuroxime, and ceftazidime. Primary cultures of confluent rabbit corneal epithelial cells were established, and each antibiotic was added at 5, 30, and 60 min at final concentrations of 16.5, 33, 66, 132, and 264 mg/ml. [3H]Thymidine incorporation then was measured and expressed as percentage inhibition of control cultures. The minimal inhibitory concentrations (MICs) for each cephalosporin in complete medium were compared to MICs determined in Mueller-Hinton broth. At in vitro drug concentrations used topically in clinical trials (33 mg/ml), no significant inhibition of [3H]thymidine incorporation was observed with cefazolin and ceftazidime at all exposure times, except 60 min. At the higher concentrations (132 and 264 mg/ml), both cefazolin and ceftazidime showed significant toxicity at all exposure times, except 5 min. Cefuroxime was toxic at all concentrations for all exposure times studied, except 16.5 mg/ml for 5 min.Ceftazidime was 100-times more potent than cefazolin and cefuroxime against 10 common corneal bacterial pathogens, including Sraphylococcus aureus and Pseudomonas aeruginosa. Based on this in vitro model, cefazolin and ceftazidime are the preferred topical cephalosporin agents and the use of cefuroxime should be discouraged.