Injectable agents and hearing loss in the treatment of patients with rifampicin-resistant tuberculosis: a nationwide multicenter prospective study.

BACKGROUND: Monitoring for hearing loss is an integral component of active tuberculosis drug-safety monitoring and management, enabling the evaluation of injectable drug doses and risk factors associated with treatment-emergent hearing loss. METHODS: Pure-tone audiometry was performed at baseline and monthly. Brock classification was used to classify the severity of hearing loss. The cumulative doses and body weight standardized cumulative doses was quantified. Cox proportional hazards models were constructed for assessment of factors associated with treatment-emergent hearing loss. RESULTS: Of the 196 patients without severe hearing loss at baseline, 89 (45.4%) had treatment-emergent hearing loss and 46 (23.5%) had treatment-emergent severe hearing loss. In multivariable analysis, aged more than 65 years old (adjHR 13.31, 95% CI 3.78-46.85) and mild hearing loss at baseline (adjHR 2.98, 95% CI 1.12-7.96) were significantly associated with treatment-emergent severe hearing loss. The minimum cumulative doses of injectable agents used was 3.2 g in those without gradable treatment-emergent hearing loss, 11.6 g in those with mild treatment-emergent hearing loss, 32.4 g in those with moderate hearing loss was, and 9.8 g in those with severe hearing loss (Kruskal-Wallis rank sum test, p-value = 1.00); and the minimum body weight standardized cumulative doses were 100, 200, 500, and 100 mg/kg, respectively (Kruskal-Wallis rank sum test: p-value = 0.84). CONCLUSION: Treatment-emergent hearing loss was common and may occur at relatively low cumulative doses of injectable agents used. Whenever injectables are indicated, it is pivotal for TB programmes to establish robust protocols for monitoring ototoxicity.