Evidence-based Definition for Extensively Drug-Resistant Tuberculosis

Maroussia Roelens, Giovanni Battista Migliori, Liudmila Rozanova, Janne Estill, Jonathon R Campbell, J Peter Cegielski, Simon Tiberi, Domingo Palmero, Greg J Fox, Lorenzo Guglielmetti, Giovanni Sotgiu, James C M Brust, Didi Bang, Christian Lienhardt, Christoph Lange, Dick Menzies, Olivia Keiser, Mario Raviglione

Abstract

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.

Original languageEnglish
Article number3527OC
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume204
Issue number6
Pages (from-to)713-722
Number of pages10
ISSN1073-449X
DOIs
Publication statusPublished - 15 Sept 2021

Keywords

  • Adult
  • Aged
  • Antitubercular Agents/therapeutic use
  • Databases, Factual
  • Diarylquinolines/therapeutic use
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Extensively Drug-Resistant Tuberculosis/diagnosis
  • Female
  • Fluoroquinolones/therapeutic use
  • Humans
  • Isoniazid/therapeutic use
  • Linezolid/therapeutic use
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Rifampin/therapeutic use
  • Treatment Outcome

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