Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

Abstract

The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.

Keywords: antibiotic resistance; antimicrobial safety; tuberculosis.

FIG 1

Flow diagram showing injectable agent use in cohort.

FIG 2

Predicted proportions (identified on the y axis) surviving without hearing loss by initial choice of injectable agent. The middle thick line represents the predicted proportion, and the outer thin lines represent 95% confidence intervals.