Anti-Tuberculous Medications and Hearing Loss
Primary Culprits
Aminoglycoside antibiotics—specifically streptomycin, amikacin, and kanamycin—are the anti-tuberculous medications most commonly associated with hearing loss, with amikacin showing the highest incidence at 33.4% of treated patients. 1, 2
Specific Agents and Their Ototoxicity Risk
Aminoglycosides (Highest Risk)
Amikacin causes hearing loss in approximately 33.4% of patients, representing the highest risk among injectable TB drugs 2. High-frequency hearing loss occurs in up to 24% of patients, with rates increasing with longer treatment duration and higher cumulative doses 1, 3. The potency order for ototoxicity among aminoglycosides is: neomycin > gentamicin > streptomycin > kanamycin > amikacin > tobramycin 4.
Streptomycin produces ototoxicity affecting both vestibular function (causing balance problems) and cochlear function (causing hearing loss) 1. The risk increases significantly with age, cumulative doses above 100-120 grams, and concurrent use of loop diuretics 1. Streptomycin is contraindicated in pregnancy due to risk of fetal hearing loss 1.
Kanamycin causes deafness but produces less vestibular dysfunction than streptomycin 1. Research demonstrates kanamycin is markedly ototoxic even at "safe" administration levels 5.
Capreomycin (Moderate Risk)
Capreomycin shares the same ototoxicity profile as aminoglycosides despite being a different drug class 1. However, it shows the lowest incidence of hearing loss at only 2.0% among injectable agents 2. The ototoxicity can be vestibular (balance loss) or cochlear (hearing loss), and may be severe and irreversible 1.
Mechanism and Clinical Characteristics
The mechanism involves presynaptic reduction of calcium uptake and inhibition of acetylcholine release, plus postsynaptic receptor binding 4. For aminoglycosides generally, ototoxicity occurs in 2-14% of patients (2-10% cochlear, 3-14% vestibular) 1.
A critical pitfall: ototoxicity can progress even after the drug is stopped 1. This irreversibility makes prevention through monitoring absolutely essential rather than optional.
Essential Monitoring Protocol
Baseline Requirements
Ongoing Monitoring
- Monthly high-quality audiometry 1
- Monthly assessment of renal function 1
- Monthly questioning regarding auditory or vestibular symptoms 1
- Repeat audiogram and vestibular testing immediately if symptoms develop 1, 3
- Drug level monitoring to avoid toxicity 1, 3
Risk Factors Requiring Extra Vigilance
- Age over 59 years (requires dose reduction to 10 mg/kg/day for streptomycin and amikacin) 1
- Renal insufficiency or ESRD 1, 3
- Concurrent use of loop diuretics (furosemide, ethacrynic acid) 1
- Higher cumulative doses 1, 3
- Baseline elevated creatinine 1, 3
- Concurrent nephrotoxic agents 1, 3
Comparative Nephrotoxicity Context
Nephrotoxicity occurs less commonly with streptomycin than with amikacin, kanamycin, or capreomycin 1. Amikacin causes renal impairment in 8.7% of patients overall, but only 3.4% in those without risk factors 1, 3.
Current Treatment Paradigm Shift
The World Health Organization updated guidelines in 2018 to advise against routine use of ototoxic second-line injectable drugs (amikacin, capreomycin, kanamycin) for multidrug-resistant TB 6. This represents a major shift recognizing that hearing loss should no longer be considered an unavoidable harm in MDR-TB treatment 6.