Second-line injectable drugs for rifampicin-resistant tuberculosis: better the devil we know?

In its 2020 guidelines for the treatment of rifampicin-resistant TB (RR-TB), the WHO recommends all-oral fluoroquinoLone-based regimens, with bedaquiline replacing the second-line injectable drugs (SLIDs). SLIDs were used for their strong acquired resistance-preventing activity. Data from three cohorts showed acquired bedaquiline resistance ranging between 2.5% and 30.8%, with no protection from a SLID in most cases. If bedaquiline resistance is that easily acquired, it will fail to protect fluoroquinolones and other drugs from acquiring resistance. Until evidence on resistance-preventing activity shows that SLIDs can safely be replaced, we call for more prudent use of the few potent second-line TB drugs available. Studies on new treatment regimens need to prioritize the prevention of acquired resistance along with treatment success. Meanwhile, reducing the dosing of SLIDs to thrice weekly from Day 1, and their replacement for any degree of audiometry abnormalities before or during treatment will largely avoid serious ototoxicity.

Automated summary

The WHO's 2020 guidelines recommend all-oral fluoroquinoLone-based regimens for rifampicin-resistant TB, with bedaquiline replacing SLIDs. Data shows high acquired resistance rates for bedaquiline, indicating SLIDs' inability to protect against it.