A New, Evidence-Based Definition for Extensively Drug-Resistant Tuberculosis

Researchers have suggested a new definition of extensively drug-resistant tuberculosis (XDR-TB) as multidrug resistant (MDR) plus additional resistance to fluoroquinolones (FQ) plus bedaquiline and/or linezolid based on a study published in the American Journal of Respiratory and Critical Care Medicine.

Until 2020, XDR-TB was defined as resistance to rifampicin and isoniazid (multidrug-resistant tuberculosis [MDR-TB]), any FQ, and any second-line injectable drug (SLID). In 2019, the World Health Organization (WHO) issued new recommendations for managing patients with drug-resistant tuberculosis, substantially limiting the role of SLID in MDR-TB treatment and thus putting the XDR-TB definition into question.

To suggest an up-to-date definition for XDR-TB, researchers used a large dataset to assess treatment outcomes for patients with MDR-TB who had been exposed to any type of longer regimen. The researchers included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results and performed a logistic regression to estimate adjusted odds ratios (aORs) for unfavorable treatment outcomes (failure, relapse, death, loss to follow-up) by resistance pattern (FQ, SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, bedaquiline).

The researchers included 11,666 patients with MDR-TB, of whom 4653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs was found to increase the odds of an unfavorable treatment outcome, and administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQ and/or SLID.

Among patients with XDR-TB, compared with persons receiving no Group A drug, aORs for unfavorable outcome were 0.37 with linezolid only, 0.40 with bedaquiline only, and 0.21 with both.

“In conclusion, our study confirmed the effectiveness of the combination of bedaquiline and linezolid in the treatment of all forms of pulmonary MDR-TB, adding information towards new definitions that are useful for clinical management of drug-resistant tuberculosis,” stated the study authors.

Reference

Roelens M, Migliori GB, Rozanova L, et al. Evidence-based definition for extensively drug-resistant tuberculosis. Am J Respir Crit Care Med. Published online June 8, 2021. DOI:10.1164/rccm.202009-3527OC