Ototoxic effect of daptomycin applied to the guinea pig middle ear

Acta Otolaryngol. 2014 Jul;134(7):679-83. doi: 10.3109/00016489.2014.898186. Epub 2014 May 19.

Abstract

Conclusion: Daptomycin applied topically at a concentration of 50 mg/ml caused mild but statistically significant hearing impairment. Outer hair cells were not damaged by daptomycin. Great care must be taken when there is a chance that daptomycin can reach the middle ear.

Objective: Ototopic antibiotic eardrops are frequently used to treat external and middle ear infections. Daptomycin is a new anti-methicillin-resistant Staphylococccus aureus (MRSA) drug with unknown ototoxicity. The current study examined the ototoxic effect of daptomycin in topical applications to guinea pig ears.

Methods: Twenty-three male Hartley guinea pigs (weight, 250-640 g) were divided into three groups receiving daptomycin (50 mg/ml), gentamicin (50 mg/ml, positive control), or saline solution (negative control). After insertion of a pressure-equalizing tube, pretreatment auditory brainstem responses (ABRs) were obtained. Topical solutions of 0.1 ml were applied through the tube into the middle ear twice a day for 7 days. Post-treatment ABRs were obtained 7 days after the last treatment. Hair cell loss was investigated with whole-mount cochlear surface preparations.

Results: The saline-treated (negative control) group showed no deterioration of ABR threshold. The daptomycin-treated group showed mild deterioration and the gentamicin-treated group showed severe deterioration in ABR threshold. Hair cells were preserved in the daptomycin- and saline-treated groups but severely damaged in the gentamicin group.

Keywords: Drug-resistant; eardrop; hearing; methicillin-resistant Staphylococcus aureus; topical; vancomycin.

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / toxicity*
  • Daptomycin / administration & dosage
  • Daptomycin / toxicity*
  • Disease Models, Animal
  • Ear, Middle / drug effects*
  • Evoked Potentials, Auditory, Brain Stem / drug effects*
  • Guinea Pigs
  • Hair Cells, Auditory / drug effects
  • Hearing Loss / chemically induced*
  • Male

Substances

  • Anti-Bacterial Agents
  • Daptomycin