INHIBITION OF PROTEASES IN PSEUDOMONAS OTITIS-MEDIA IN CHINCHILLAS

The treatment of chronic suppurative otitis media caused by Pseudomona s aeruginosa remains a challenging problem, The virulence of Pseudomon as is related to its secretion of two matrix metalloproteinases, alkal ine protease and elastase. This experiment examines the effects of a s ynthetic inhibitor of matrix metalloproteinases GM 6001, or N-(2(R)-2- (hydroxyamido carbonylmethyl)-d-methylpentanoyl)-L-tryptophane methyla mide), in a chinchilla Pseudomonas otitis media model. Thirty chinchil las underwent bilateral subtotal tympanic membrane perforations. Twent y-four chinchillas underwent bilateral middle ear inoculation with P. aeruginosa. Chinchillas were divided into four groups of six animals a fter the establishment of otitis media. Animals in one group were cont rols; the other three groups received either gentamicin, GM 6001, or g entamicin plus GM 6001 into the external auditory canal three times da ily for 4 weeks. Clearance of Pseudomonas infection occurred in three ears of three animals, all in gentamicin groups, with or without GM 60 01. Otorrhea (p = 0.0014) and external canal erythema (p = 0.025) were mild in the two gentamicin groups and moderate in the GM 6001 group w hen compared with bacterial controls. Animals in the GM 6001 group had the highest survival rate, less severe facial paralysis, and less ves tibular toxicity than the gentamicin, gentamicin plus GM 6001, or cont rol groups, although these differences were not statistically signific ant. This pilot study showed encouraging results for a role of ototopi cal protease inhibitors in the treatment of Pseudomonas otitis media.