High-dose amikacin in the first week of all-oral rifampicin-resistant TB treatment is safe: a single-arm trial

BACKGROUND: Effective rifampicin-resistant TB (RR-TB) treatment should prevent resistance development. Bedaquiline is central to all-oral regimens, but it is threatened by rising resistance, possibly due to its delayed bactericidal effect. We evaluated the safety of strengthening the 1st week of all-oral RR-TB treatment with amikacin.

METHODS: In a single-arm trial, 20 RR-TB patients received two intramuscular doses of amikacin (30 mg/kg) with lidocaine on the first and fourth day of treatment. The assumption was that none of the 20 patients would experience a grade 3-4 amikacin-related adverse event, corresponding to a primary hypothesis that less than 14% of patients have a grade 3-4 adverse event related to amikacin. Nephrotoxicity, ototoxicity, and pain post-injection were monitored. Early bactericidal effect and amikacin pharmacokinetics were measured.

RESULTS: None of the 20 patients experienced a grade 3-4 adverse event during the first 2 weeks of treatment (95% confidence interval: 0-0.139). No hearing loss of any grade was observed. Pain assessment post-injections was minimal. Amikacin became undetectable within a median of 11 h.

CONCLUSION: The intervention with high-dose amikacin in the 1st week of all-oral regimen was safe in this small cohort. A multi-country study is justified to investigate the efficacy to prevent acquired resistance.