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Population implications of the use of bedaquiline in people with extensively drug-resistant tuberculosis: are fears of resistance justified?

Abstract

Global rollout of the new antituberculosis drug bedaquiline has been slow, in part reflecting concerns about spread of bedaquiline resistance. Acquired resistance to bedaquiline is especially likely in patients with extensively drug-resistant (XDR) tuberculosis. However, the very high mortality rates of patients with XDR not receiving bedaquiline, and promising cohort study results, suggest these patients also have greatest need for the drug. In this Personal View, we argue that resistance concerns should not forestall use of bedaquiline in patients with XDR tuberculosis. Our position in favour of increased access to bedaquiline for these patients is based on three arguments. First, the use of drug combinations that include bedaquiline might prevent spread of XDR disease to others in the community. Second, until new combination regimens of novel drugs for XDR tuberculosis become available, patients with XDR disease and their infected contacts will face equivalent outcomes if bedaquiline is either not provided because of policy, or not effective because of resistance. Finally, because resistance to bedaquiline and other antituberculosis drugs is caused by mutations within a single bacterial chromosome, use of bedaquiline in patients with XDR tuberculosis will not substantially increase the risk of bedaquiline resistance in patients with drug-susceptible or multidrug-resistant (non‑XDR) tuberculosis strains.

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