Endothelial toxicity of ceftazidime in anterior chamber irrigation solution

Due to the high toxicity of aminoglycoside antibiotics, many authors prefer to use third generation cephalosporines in the prophylaxis and treatment of intraocular infections. The aim of the present study was to determine safe ceftazidime levels in anterior chamber irrigation solution. Twenty-two eyes of 12 white New Zealand rabbits were divided into six groups of two animals each. Double paracentesis was performed in both eyes, irrigating the right eye with 250 ml of BSS-Plus (BSS+) solution, and the left eye with 250 ml of BSS+ solution with increasing concentrations of ceftazidime (2, 3, 4, 6 and 8 mg ml-1). Each rabbit was killed at the end of surgery, except the last group, which received BSS+ and BSS+ with 8 mg ml-1 of ceftazidime, respectively, in one eye, and were then killed 24 hr later. Endothelial lesions were assessed by silver nitrate staining. We considered lesions endothelial silver affinity ranging from minimal (1-2+) to intense (3-4+). 1-2+ silver affinity was found in 4 +/- 1.35% of endothelial cells in the controls; this percentage in turn increased with antibiotic concentration (6.1 +/- 1.13%, 6.7 +/- 0.4%, 7.2 +/- 1.36%, 7.3 +/- 1.93% and 7.5 +/- 1.83%, respectively). The percentage of 3-4+ silver affinity was 0.18 +/- 0.17% in the controls, and likewise increased with antibiotic concentration (0.22 +/- 0.11%, 0.37 +/- 0.09%, 2.8 +/- 0.63% and 3.1 +/- 0.46%, respectively). The increase in affinity was greatest up to the 4 mg ml-1 concentration. In the last group there were zones of endothelial alterations in morphology and size, with signs of attempted repair in the eye treated with antibiotic, but none in the case treated only with BSS+. Ceftazidime concentrations above 3 mg ml-1 in intraocular infusions induce endothelial cell toxicity.