TY - JOUR
T1 - Evidence-based Definition for Extensively Drug-Resistant Tuberculosis
AU - Roelens, Maroussia
AU - Battista Migliori, Giovanni
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
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 - Adult
KW - Aged
KW - Antitubercular Agents/therapeutic use
KW - Databases, Factual
KW - Diarylquinolines/therapeutic use
KW - Drug Administration Schedule
KW - Drug Resistance, Multiple, Bacterial
KW - Drug Therapy, Combination
KW - Extensively Drug-Resistant Tuberculosis/diagnosis
KW - Female
KW - Fluoroquinolones/therapeutic use
KW - Humans
KW - Isoniazid/therapeutic use
KW - Linezolid/therapeutic use
KW - Logistic Models
KW - Male
KW - Middle Aged
KW - Odds Ratio
KW - Rifampin/therapeutic use
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85115617534&partnerID=8YFLogxK
U2 - 10.1164/rccm.202009-3527OC
DO - 10.1164/rccm.202009-3527OC
M3 - Journal article
C2 - 34107231
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
M1 - 3527OC
ER -