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Home / The International Journal of Tuberculosis and Lung Disease, Volume 24, Number 1

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

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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 (<75 mg/kg/week, 95%CI 1.09–1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01–1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29–2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01–1.33) were also associated with an increased risk of hearing loss.

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.

Keywords: cumulative hazard; ototoxicity; survival analysis

Document Type: Research Article

Affiliations: 1: Johns Hopkins University School of Nursing, Baltimore, MD, The REACH Initiative, Johns Hopkins University School of Nursing, Baltimore, MD 2: Departments of Epidemiology and International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 3: Divisions of Clinical Pharmacology and Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD 4: Division of Head and Neck Surgery and Communication Sciences, Duke University School of Medicine, Durham, NC 5: Johns Hopkins University School of Nursing, Baltimore, MD 6: Johns Hopkins University School of Nursing, Baltimore, MD, Center for Cardiovascular and Chronic Care, Johns Hopkins University, Baltimore, MD, USA

Publication date: January 1, 2020

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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