UC San Diego

Aminoglycoside antibiotics (AGs) are used to treat infections in live-stranded odontocetes. Although AGs have high clinical efficacy, they can be ototoxic, especially to high frequency hearing. This hearing loss is often irreversible and warrants concern because it is likely to affect odontocete echolocation and communication. AGs have a low toxicity threshold and thus a narrow therapeutic window. Common terrestrial mammal dosing protocols could be inappropriate for odontocetes because they may have a reduced ability to clear AGs. Poor health, common in stranded odontocetes, compounds this problem. It may also compromise intrinsic mechanisms that maintain homeostasis and postpone cochlear hair cell death. These factors can further narrow the therapeutic window, causing otherwise safe drug levels to become toxic. There are several effective ways of attenuating AG ototoxicity such as minimizing the area under the concentration-time curve by extending dosage intervals. Therapeutic monitoring and additive therapies can additionally reduce ototoxicity. Until ototoxic risk and risk reduction strategies are explored in odontocetes, it is safest to test a stranded animal's hearing prior to its release. Hearing loss may only present weeks after treatment cessation due to AG cytotoxicity characteristics and compensatory mechanisms thereof. AGs have a protracted cochlear elimination half- life that may cause hearing loss to worsen for months after treatment. Developing strategies for reducing ototoxic risk, determining prevalence of ototoxicity in stranded animals, and documenting the functional effects of hearing loss would make it easier to estimate the odds of post-release survival in AG-treated odontocetes