The adverse effects and choice of injectable agents in MDR-TB: amikacin or capreomycin [PublishAheadOfPrint]

Background: The prolonged use of injectable agents in an MDR-TB regimen is recommended by the WHO despite association with ototoxicity and nephrotoxicity.

Objective: We undertook this study to look at the relative adverse effects of capreomycin and amikacin.

Methods: We reviewed the case notes of 100 consecutive patients treated at 4 MDR-TB treatment centres in the UK.

Results: The median total duration of treatment with an injectable agent was 178 (IQR 109-192, n=73) days for those with MDR-TB, 179 (104-192, n=12) days for those with MDR-TB plus fluoroquinolone resistance and 558 (324-735, n=8) days for those with XDR-TB. Injectable use was longer for those started with capreomycin at 183 (IQR 123-197) days compared to 119 (IQR 83-177) days with amikacin (p=0.002). Excluding XDR-TB, 51 (51/85, 60%) patients were treated with an injectable for over 6 months and 12 (12/85, 14%) for over 8 months. 40 % of all patients discontinued the injectable due to hearing loss. 55% of patients experienced ototoxicity: 5 times (hazard ratio (HR) 5.2, CI 1.2-22.6, p=0.03) more likely in those started on amikacin compared to treatment with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (Odds ratios: 0.28 (0.11-0.72)), with 5 (5/37, 14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number experiencing a creatinine rise of > 1.5 times baseline.

Conclusion: Hearing loss is frequent in this cohort, though significantly lower in those starting capreomycin which should be given greater consideration as a first line agent.

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