Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring. OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB. DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa. RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group ( CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.