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Experimental animal models for studying antimicrobial pharmacokinetics in otitis media
D M Canafax1, N Nonomura, G R Erdmann
1University of Minnesota Otitis Media Research Center, Minneapolis 55455.
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.
Insights
This study used a chinchilla model to measure antibiotic levels in middle ear fluid during otitis media. Findings provide crucial data for optimizing antimicrobial dosing in ear infections.
Area of Science:
- Pharmacology
- Otolaryngology
- Infectious Diseases
Background:
- Antimicrobial treatment for otitis media relies heavily on empiric dosing.
- Limited pharmacologic studies exist on drug distribution into the middle ear.
- A validated chinchilla model is essential for studying otitis media pathogenesis.
Purpose of the Study:
- To adapt a chinchilla model for assessing antibiotic penetration into middle ear effusion.
- To evaluate the distribution of amoxicillin, trimethoprim, and sulfamethoxazole in serous and purulent otitis media.
- To establish a reliable method for measuring drug concentrations in middle ear fluid.
Main Methods:
- Induction of purulent otitis media via Streptococcus pneumoniae inoculation.
- Induction of serous otitis media using eustachian tube obstruction.
- Administration of amoxicillin, trimethoprim, and sulfamethoxazole to affected chinchillas.
- Quantification of plasma and middle ear fluid drug concentrations using liquid chromatography.
Main Results:
- The chinchilla model successfully replicated serous and purulent otitis media.
- Measurable concentrations of amoxicillin, trimethoprim, and sulfamethoxazole were found in middle ear effusions.
- The study demonstrated the model's utility in assessing antibiotic penetration.
Conclusions:
- The chinchilla model is valuable for pharmacologic studies of middle ear infections.
- This research provides a foundation for evidence-based antimicrobial dosing in otitis media.
- Further studies can utilize this model to optimize antibiotic selection and dosage for ear infections.