Pharmacokinetics and other risk factors for kanamycin-induced hearing loss in patients with multi-drug resistant tuberculosis

OBJECTIVE: The toxicity associated with the use of kanamycin includes irreversible hearing loss. There is limited data describing the relationship between hearing loss and kanamycin pharmacokinetics (PK). We explored the association of kanamycin PK with hearing loss in patients on MDR-TB treatment. DESIGN: We prospectively recruited patients on kanamycin-based MDR-TB treatment in Cape Town. Hearing thresholds from 0.25 to 16 kHz were tested at baseline and at 4, 8 and 12 weeks. We determined kanamycin concentrations at steady-state in serial plasma samples over 10 hours, and explored factors associated with hearing loss. STUDY SAMPLE: One hundred and two participants including 58 (56.9%) men had analysable audiometric data; median age was 34.9 years, 65 (63.7%) were HIV-positive, and 24 (23.5%) had been treated for MDR-TB previously. RESULTS: Eighty-four participants (82.4%) developed hearing loss. We found a 3% (95% CI: 1 to 6%, p=0.028) increased risk of cochleotoxicity for each 10μg•hr/L increase in 0–10 hour AUC. CONCLUSION: We describe a high incidence of hearing loss in MDR-TB patients treated with kanamycin, with higher AUC(0–10) significantly associated with hearing loss.