The treatment of chronic
suppurative otitis media caused by Pseudomonas aeruginosa remains a challenging problem. The virulence of Pseudomonas is related to its secretion of two
matrix metalloproteinases,
alkaline protease and
elastase. This experiment examines the effects of a synthetic inhibitor of
matrix metalloproteinases GM 6001, or N-(2(R)-2(hydroxyamido carbonylmethyl)-4-methylpentanoyl)-L-tryptophane methylamide), in a chinchilla Pseudomonas
otitis media model. Thirty chinchillas underwent bilateral subtotal tympanic membrane perforations. Twenty-four chinchillas underwent bilateral middle ear inoculation with P. aeruginosa. Chinchillas were divided into four groups of six animals after the establishment of
otitis media. Animals in one group were controls; the other three groups received either
gentamicin,
GM 6001, or
gentamicin plus
GM 6001 into the external auditory canal three times daily for 4 weeks. Clearance of
Pseudomonas infection occurred in three ears of three animals, all in
gentamicin groups, with or without
GM 6001. 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 when compared with bacterial controls. Animals in the
GM 6001 group had the highest survival rate, less severe
facial paralysis, and less vestibular toxicity than the
gentamicin,
gentamicin plus
GM 6001, or control groups, although these differences were not statistically significant. This pilot study showed encouraging results for a role of ototopical
protease inhibitors in the treatment of Pseudomonas
otitis media.