The Lancet Respiratory Medicine Commission on drug-resistant tuberculosis was published
in 2017, which comprehensively reviewed and provided recommendations on various aspects
of the disease. Several key new developments regarding drug-resistant tuberculosis
are outlined in this Commission Update. The WHO guidelines on treating drug-resistant
tuberculosis were updated in 2019 with a reclassification of second line anti-tuberculosis
drugs. An injection-free MDR tuberculosis treatment regimen is now recommended. Over
the past 3 years, advances in treatment include the recognition of the safety and
mortality benefit of bedaquiline, the finding that the 9-11 month injectable-based
'Bangladesh' regimen was non-inferior to longer regimens, and promising interim results
of a novel 6 month 3-drug regimen (bedaquiline, pretomanid, and linezolid). Studies
of explanted lungs from patients with drug-resistant tuberculosis have shown substantial
drug-specific gradients across pulmonary cavities, suggesting that alternative dosing
and drug delivery strategies are needed to reduce functional monotherapy at the site
of disease. Several controversies are discussed including the optimal route of drug
administration, optimal number of drugs constituting a regimen, selection of individual
drugs for a regimen, duration of the regimen, and minimal desirable standards of antibiotic
stewardship. Newer rapid nucleic acid amplification test platforms, including point-of-care
systems that facilitate active case-finding, are discussed. The rapid diagnosis of
resistance to other drugs, (notably fluoroquinolones), and detection of resistance
by targeted or whole genome sequencing will probably change the diagnostic landscape
in the near future.