Treatment of Highly Drug-Resistant Pulmonary Tuberculosis

In an open-label study (n=109) in which follow-up is ongoing at three South African sites, combination of bedaquiline, pretomanid and linezolid led to a favourable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of TB

SPS commentary:

The primary end point was the incidence of an unfavourable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavourable outcome and 98 patients (90%) had a favourable outcome.

According to an editorial, the successful development of two new antituberculosis drugs — bedaquiline and pretomanid — represents an important step forward in the pursuit of pan-tuberculosis regimens fit for the 21st century. It notes that cure rates for extensively drug-resistant TB were less than 50% before the advent of new drugs, therefore, this is a triumph, and the authors are to be congratulated for their vision and courage in tackling the most difficult-to-treat forms of TB. It adds however that the tragedy being confronted, is the overlapping realities of the persisting need for new regimens and the spectacular inadequacy of support for their development and the tools needed for their effective use in the field. It alludes to the current TB regimen, which was the product of a remarkable series of global, iterative, RCTs conducted between 1947 and 1980, with the resulting “short-course chemotherapy” consisting of an oral regimen, containing rifampin, isoniazid, and pyrazinamide, that cured the large majority of people with TB if it was taken for 6 months, and despite known toxicities, has produced extraordinary gains, curing approximately 58 million people since the year 2000, but 30 years of its global use has revealed serious limitations of depending on a single, one-size-fits-all regimen to treat a challenging infectious disease.


New England Journal of Medicine

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