Toxicity and clearance of intravitreal cefotetan

Abstract

Direct intravitreal injection of antibiotics plays an important role in the management of bacterial endophthalmitis. In the present study we investigated the toxicity and clearance of intravitreally injected cefotetan in a rabbit model. No toxic ocular side effects could be detected by electroretinography (ERG) or light and electron microscopy up to and including a single intravitreal dose of 1000 micrograms. Intravitreal injection of 2000 micrograms cefotetan resulted in mild degeneration of photoreceptor outer segments and, sporadically, in cataract formation. After intravitreal injection of 4000 micrograms, moderate toxic degeneration of photoreceptors occurred, with displacement and mitochondrial swelling of inner segments. In addition, lysosomal lamellar inclusion bodies could be detected in pigment epithelial cells. After a single intravitreal injection of 1000 micrograms cefotetan, concentrations greater than the minimum necessary for the inhibition of most commonly occurring intraocular pathogens (except Pseudomonas aeruginosa and Staphylococcus epidermidis) were maintained in the vitreous humor for greater than 48 h. Cefotetan may be a potentially important drug for intravitreal injection, especially in cases of gram-negative and suspected anaerobic endophthalmitis.