Experimental animal models for studying antimicrobial pharmacokinetics in otitis media

Abstract

Antimicrobial treatment of otitis media, especially drug dosing considerations, is largely empiric, with few reported pharmacologic studies of drug distribution into the middle ear. A chinchilla animal model of serous and purulent otitis media has been used for some time to investigate mechanisms of disease pathogenesis. This model was adapted to investigate the penetration of amoxicillin, trimethoprim, and sulfamethoxazole into middle ear effusion. Purulent otitis media was produced by direct middle ear inoculation with type 7F Streptococcus pneumoniae. Serous otitis media was produced by eustachian tube obstruction using silastic sponge or Coeflex cement, but the Coeflex caused an undesirable local inflammatory response. The three antibiotics were administered to chinchillas with serous and purulent middle ear effusion. Plasma and ear fluid drug concentrations were measured by liquid chromatography and demonstrated the value of this model in assessing antibiotic penetration.