TY - JOUR
T1 - Evidence-based definition for extensively drug-resistant tuberculosis
AU - Roelens, Maroussia
AU - Migliori, Giovanni Battista
AU - Rozanova, Liudmila
AU - Estill, Janne
AU - Campbell, Jonathon R.
AU - Cegielski, J. Peter
AU - Tiberi, Simon
AU - Palmero, Domingo
AU - Fox, Greg J.
AU - Guglielmetti, Lorenzo
AU - Sotgiu, Giovanni
AU - Brust, James C.M.
AU - Bang, Didi
AU - Lienhardt, Christian
AU - Lange, Christoph
AU - Menzies, Dick
AU - Keiser, Olivia
AU - Raviglione, Mario
N1 - Funding Information:
Supported by Schweizerischer Nationalfonds zur Fo€rderung der Wissenschaftlichen Forschung grant 163878 (M. Roelens and O.K.) and the Deutsches Zentrum fu€r Infektionsforschung (C. Lange). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had access to all of the data in the study and had final responsibility for the decision to submit for publication. The findings and conclusions are those of the authors and do not necessarily represent the views of the U.S. CDC.
Publisher Copyright:
© 2021 American Thoracic Society. All rights reserved.
PY - 2021/9/15
Y1 - 2021/9/15
N2 - 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.
AB - 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.
KW - Drug resistance
KW - Epidemiology
KW - Meta-analysis
KW - Tuberculosis
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U2 - 10.1164/rccm.202009-3527OC
DO - 10.1164/rccm.202009-3527OC
M3 - Article
C2 - 34107231
AN - SCOPUS:85115617534
SN - 1073-449X
VL - 204
SP - 713
EP - 722
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 6
ER -
