Maroussia Roelens1, Giovanni Battista Migliori2, Liudmila Rozanova1, Janne Estill1,3, Jonathon R Campbell4, J Peter Cegielski5, Simon Tiberi6,7, Domingo Palmero8, Gregory J Fox9, Lorenzo Guglielmetti10,11, Giovanni Sotgiu12, James C M Brust13, Didi Bang14,15, Christian Lienhardt16,17, Christoph Lange18,19,20, Dick Menzies21, Olivia Keiser1, Mario Raviglione22,23. 1. University of Geneva Institute of Global Health, 30492, Geneve, Switzerland. 2. Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy. 3. University of Bern, 27210, Institute of Mathematical Statistics and Actuarial Science, Bern, Switzerland. 4. McGill University, 5620, Montreal, Quebec, Canada. 5. Rollins School of Public Health, 25798, Department of Epidemiology, Atlanta, Georgia, United States. 6. Queen Mary University of London Barts and The London School of Medicine and Dentistry, 4952, Blizard Institute, London, United Kingdom of Great Britain and Northern Ireland. 7. Barts Health NHS Trust, 9744, Division of Infection, Royal London Hospital, London, United Kingdom of Great Britain and Northern Ireland. 8. Hospital F. J. Muñiz, Buenos Aires, Argentina. 9. University of Sydney, Sydney, New South Wales, Australia. 10. Sorbonne Universite, 27063, Centre d'Immunologie et des Maladies Infectieuses, Paris, France. 11. APHP, 26930, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Paris, France. 12. University of Sassari, 9312, Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, Sassari, Italy. 13. Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, New York, United States. 14. Statens Serum Institut, 4326, Kobenhavn, Denmark. 15. Copenhagen University Hospital, 53146, Department of Clinical Microbiology, Kobenhavn, Denmark. 16. Unité Mixte Internationale TransVIHMI , (Université de Montpellier, UMI 233 IRD, U1175 INSERM), Institut de Recherche pour le Développement (IRD), Montpellier, France. 17. London School of Hygiene and Tropical Medicine, Epidemiology and Population Health, Department of Infectious Disease Epidemiology, London, United Kingdom of Great Britain and Northern Ireland. 18. Research Center Borstel, German Center for Infection Research (DZIF) Clinical Tuberculosis Center, Borstel, Germany. 19. University of Lübeck, Respiratory Medicine & International Health, Lübeck, Germany. 20. Baylor College of Medicine, 3989, Global TB Program, Houston, Texas, United States. 21. McGill University, 5620, McGill International TB Centre, Montreal, Quebec, Canada. 22. University of Milan, 9304, Centre for Multidisciplinary Research in Health Science, Milano, Italy. 23. University of Geneva Global Studies Institute, 87659, Geneve, Switzerland; raviglionemc@gmail.com.
Abstract
RATIONALE: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as resistance to rifampicin and isoniazid (multidrug-resistant tuberculosis, MDR-TB), any fluoroquinolone (FQ) and any second-line injectable drug (SLID). In 2019 the World Health Organization issued new recommendations for managing patients with drug-resistant tuberculosis, substantially limiting the role of SLID in MDR-TB treatment and thus putting that XDR-TB definition into question. OBJECTIVE: To propose an up-to-date definition for XDR-TB. METHODS: We used a large dataset to assess treatment outcomes for MDR-TB patients exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We did logistic regression to estimate adjusted odds ratios (aORs) for unfavourable treatment outcome (failure, relapse, death, loss-to-follow-up) by resistance pattern (FQ, SLID) and Group A drug use (moxifloxacin/levofloxacin, linezolid, bedaquiline). MEASUREMENTS AND MAIN RESULTS: We included 11,666 patients with MDR-TB; 4653 (39.9%) had an unfavourable treatment outcome. Resistance to FQs increased the odds of an unfavourable treatment outcome (aOR 1.91; 95% confidence interval [95%CI] 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQ and/or SLID. Among XDR-TB patients, compared to persons receiving no Group A drug, aORs for unfavourable 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 plus additional resistance to FQ plus bedaquiline and/or linezolid, and helps assess the adequacy of this definition for surveillance and treatment choice.
RATIONALE: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as resistance to rifampicin and isoniazid (multidrug-resistant tuberculosis, MDR-TB), any fluoroquinolone (FQ) and any second-line injectable drug (SLID). In 2019 the World Health Organization issued new recommendations for managing patients with drug-resistant tuberculosis, substantially limiting the role of SLID in MDR-TB treatment and thus putting that XDR-TB definition into question. OBJECTIVE: To propose an up-to-date definition for XDR-TB. METHODS: We used a large dataset to assess treatment outcomes for MDR-TB patients exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We did logistic regression to estimate adjusted odds ratios (aORs) for unfavourable treatment outcome (failure, relapse, death, loss-to-follow-up) by resistance pattern (FQ, SLID) and Group A drug use (moxifloxacin/levofloxacin, linezolid, bedaquiline). MEASUREMENTS AND MAIN RESULTS: We included 11,666 patients with MDR-TB; 4653 (39.9%) had an unfavourable treatment outcome. Resistance to FQs increased the odds of an unfavourable treatment outcome (aOR 1.91; 95% confidence interval [95%CI] 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQ and/or SLID. Among XDR-TB patients, compared to persons receiving no Group A drug, aORs for unfavourable 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 plus additional resistance to FQ plus bedaquiline and/or linezolid, and helps assess the adequacy of this definition for surveillance and treatment choice.
Entities:
Keywords:
Drug resistance; Epidemiology; Meta-analysis; Tuberculosis
Authors: Carla Mariner-Llicer; Galo A Goig; Laura Zaragoza-Infante; Manuela Torres-Puente; Luis Villamayor; David Navarro; Rafael Borras; Álvaro Chiner-Oms; Iñaki Comas Journal: Microb Genom Date: 2021-12