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

Only 102 of 147 recruited participants had analyzable hearing data; 45 were excluded for reasons including discharge, withdrawal, death, illness, unreliable tests or comorbid conditions. A baseline audiogram could not be obtained before treatment in all participants, which may have led to under-reporting of hearing loss. Cumulative AUC was based on sampling to 10 hours post dose and may underestimate true cumulative exposure. Information on previous aminoglycoside use and genetic factors was limited. Patients with only one hearing test or pre-existing hearing loss were excluded, and this reduced the sample size. Patients received a multi-drug MDR-TB regimen, so the contribution of any single component cannot be separated. HIV infection was present in 63.7% of the cohort, but HIV was not a significant risk factor in the univariate analysis. Prior aminoglycoside use was documented in 24 of 102 participants, but was not significantly associated with hearing loss.

The authors declared no conflict of interest regarding publication. The article metadata lists NIH extramural and non-U.S. government research support.

Do not conclude that kanamycin alone caused the hearing loss. Patients received a multi-drug MDR-TB regimen including pyrazinamide, moxifloxacin, kanamycin, terizidone and either ethionamide or isoniazid, with ethambutol added when resistance risk was considered low, so the contribution of any single component cannot be separated. Also, do not treat the 82.4% incidence as directly comparable with studies using conventional audiometry, because ultra-high frequency testing identified loss that would otherwise not be detected at conventional frequency thresholds.