Objectives: To investigate the safety and efficacy of a topical combination
of tobramycin and dexamethasone in a primate model of chronic suppurative
otitis media (CSOM) and to explore the contribution of the added topical st
eroid for the treatment of CSOM.
Design: Blinded, randomized, placebo-controlled trial.
Subjects: Sixty juvenile cynomolgus monkeys randomized into the following 6
treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0
.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33%
dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5),
and phosphate-buffered saline solution (group 6).
Interventions: Chronic suppurative otitis media was established by inoculat
ing the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, a
nimals were treated according to the group assignment with 3 drops twice da
ily for 7 weeks. Hearing thresholds were monitored with repeated auditory b
rainstem response testing (ABR), and clinical response was monitored with r
epeated otoscopic examinations and cultures throughout the study. Cytocochl
eograms were evaluated for quantification of outer hair cell loss.
Results: Rapid resolution of otorrhea and eradication of P aeruginosa occur
red in all groups receiving tobramycin. The inclusion of dexamethasone acce
lerated the resolution of otorrhea and negative yields of cultures compared
with tobramycin alone. Otorrhea and positive culture findings persisted in
the groups not treated with topical antibiotic. Results of ABRs at 4 and 8
weeks and cytocochleograms for outer cell hair loss were not affected by d
rug administration. Perilymph samples collected at the end of the study sho
wed no detectable tobramycin.
Conclusions: Combined tobramycin-dexamethasone ear drops were safe and effe
ctive in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobr
amycin.