A 64-year-old man with a history of hypertension and congestive heart failure is admitted to the hospital for a severe, multi-drug resistant urinary tract infection. He is started on intravenous vancomycin and tobramycin. Four days into his treatment course, he begins to complain of a high-pitched ringing in both ears and difficulty hearing the nursing staff. He also reports feeling slightly unsteady when walking to the restroom. His current oral medications include lisinopril, furosemide, and aspirin. Laboratory studies show a serum creatinine that has risen from 1.0 mg/dL to 1.8 mg/dL over the last 48 hours.
Which of the following medications is most likely responsible for this patient’s permanent hearing loss?
The correct answer is:
D) Tobramycin
The patient is experiencing ototoxicity, a common side effect of several classes of medications. Aminoglycosides, such as tobramycin, gentamicin, and amikacin, are notoriously ototoxic and nephrotoxic. They cause permanent sensory hair cell death in the cochlea, leading to sensorineural hearing loss and tinnitus, and the vestibular apparatus, leading to equilibrium issues. Aminoglycoside-induced ototoxicity is often irreversible because the hair cells of the inner ear do not regenerate. The patient's rising creatinine suggests concomitant nephrotoxicity, which further decreases the clearance of the drug, exacerbating its toxic effects.
Answer choice A: Aspirin, is incorrect. While high-dose salicylate therapy can cause ototoxicity, it characteristically presents as reversible tinnitus. It typically does not cause the permanent, profound sensorineural hearing loss associated with aminoglycosides.
Answer choice B: Furosemide, is incorrect. Loop diuretics can cause ototoxicity, especially when administered in high doses intravenously or in patients with advanced chronic kidney disease. However, loop diuretic-induced hearing loss is typically reversible once the medication is discontinued, unlike aminoglycoside toxicity.
Answer choice C: Lisinopril, is incorrect. ACE inhibitors are not associated with ototoxicity. Their primary side effects include cough, angioedema, hyperkalemia, and potential teratogenicity.
Answer choice E: Vancomycin, is incorrect. While traditionally labeled as ototoxic, modern purified formulations of vancomycin rarely cause hearing loss when used as monotherapy. However, it can potentiate the ototoxic effects of aminoglycosides when used in combination, as seen in this patient. Between the two, the aminoglycoside is the primary causative agent for permanent hair cell destruction.
Key Learning Point
Aminoglycosides (e.g., tobramycin) cause permanent sensorineural hearing loss and vestibular dysfunction by inducing apoptosis of inner ear hair cells. This risk is increased with prolonged therapy, renal impairment, or concomitant use of other ototoxic agents (e.g., loop diuretics, vancomycin, cisplatin). In contrast, aspirin and loop diuretics typically cause reversible ototoxicity.
