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 are 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 h, 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: 1-6%, p = 0.028) increased risk of cochleotoxicity for each 10 µg h/L increase in 0-10 h AUC.Conclusion: We describe a high incidence of hearing loss in MDR-TB patients treated with kanamycin, with higher AUC0-10 significantly associated with hearing loss.

The occurrence of auditory dysfunction in children with TB receiving ototoxic medication at a TB hospital in South Africa.

OBJECTIVES: to describe the auditory dysfunction of children with tuberculosis receiving ototoxic medication at a residential TB hospital in the Cape Town metropolitan area. METHODS: A descriptive survey research design was adopted. The auditory status of participants was evaluated by otoscopy, immittance, audiometry or OAE and AABR (depending on the age). STUDY SAMPLE: 29 in-patients (7 months to 16.6 years). RESULTS: Fifty five percent of participants presented with middle ear abnormalities (n=16) and 48% (n=12) had sensorineural or mixed hearing loss. The degree of hearing loss ranged from mild to profound in 16% of the ears. The conventional pure-tone average of .5, 1, & 2 kHz did not allow for the determination of the degree of hearing loss in the remaining 18% which had high frequency hearing loss. CONCLUSIONS: The high occurrence of hearing loss necessitates the implementation of monitoring program for children receiving ototoxic medication. Consideration should be given to using the average of hearing thresholds at 4, 6 and 8 kHz to determine the classification of degree of hearing loss in cases of ototoxicity.