Second-line injectable induced ototoxicity in drug resistant tuberculosis: A systematic review of Indian studies

Second-line injectables (SLIs) form an essential class of agents in the treatment of drug resistant (DR) tuberculosis (TB). However, their use is sometimes limited due to serious adverse events like ototoxicity and hearing loss, leading to permanent hearing loss if SLIs are continued. Globally as well as in India a wide variation in incidence of ototoxicity/hearing loss has been reported in patients with DR-TB. In this systematic analysis, we attempt to ascertain the ototoxicity of SLIs in Indian patients with multidrug resistant tuberculosis (MDR-TB) wherein ototoxicity onset was assessed using audiometry performed at both pre- and post-SLI treatment initiation. Twenty two studies were identified based on the inclusion criteria. Ototoxicity was observed in 10.12% [349/3447] patients within 3.8 ± 2.6 months of treatment initiation when the ototoxicity was assessed either with or without audiometry assessment. Only five studies reported ototoxicity assessment with PTA at both pre- and post-SLI initiation and ototoxicity was observed in 27.01% (121/448) patients in these five studies. Sensorineural loss was observed in three studies (high frequency loss: capreomycin, 25.0% [1/4 patients]; amikacin, 19.7% [12/61]; kanamycin, 13.3% [22/166]; streptomycin, 11.8% [2/17]; flat loss: amikacin, 8.2% [5/61]; streptomycin, 5.9% [1/17]; kanamycin 4.8% [8/166]). Most of the patients experiencing ototoxicity were managed by discontinuing (49.6% [120/242]) or replacing SLI treatment (40.8% [49/120]). The study identified high prevalence of ototoxicity in Indian patients with DR-TB treated with SLI when ototoxicity was monitored regularly using PTA (27.01%), warranting a need to develop unified guidelines for monitoring ototoxicity, improving physician awareness and educating patients/caregivers for reporting symptoms of hearing loss.