Treatment outcomes of extensively drug-resistant tuberculosis in Europe: a retrospective cohort study
Yousra Kherabi, Ole Skouvig Pedersen, Christoph Lange, François Bénézit, Dumitru Chesov, Luigi Ruffo Codecasa, Andrii Dudnyk, Nana Kiria, Olha Konstantynovska, Dhiba Marigot-Outtandy, Traian Constantin Panciu, Corentin Poignon, Sirje Sasi, Dagmar Schaub, Varvara Solodovnikova, Laima Vasiliauskaitė, Lusine Yeghiazaryan, Gunar Günther, Lorenzo Guglielmetti, Lorenzo Guglielmetti, Alexandra Aubry, Anca Vasiliu, Andrii Dudnyk, Anne Marie McLaughlin, Christoph Lange, Christoph Lange, Corentin Poignon, Dagmar Schaub, Daniela Cirillo, Daria Podlekareva, Dhiba Marigot-Outtandy, Dumitru Chesov, Edita Davidavičienė, François Bénézit, Giovanni Fumagalli, Giuliana Troia, Gunar Günther, Ilaria Motta, Jerker Jonsson, Jérôme Robert, Johannes Eimer, Laima Vasiliauskaitè, Liga Kuska, Lorenzo Guglielmetti, Luigi Ruffo Codecasa, Lusine Yeghiazaryan, Marcin Skowroński, Margaret Fitzgibbon, Mathieu Revest, Nana Kiria, Nicolas Veziris, Ole Skouvig Pedersen, Olha Konstantynovska, Onya Opota, Piret Viiklepp, Roxana Coriu, Simone Tunesi, Sirje Sasi, Sten Skogmar, Stephanie Bjerrum, Tamar Togonidze, Traian-Constantin Panciu, Troels Lillebaek, Valérie Pourcher, Varvara Solodovnikova, Vivian Bui Le, Yousra Kherabi
Abstract
Background: In 2021, World Health Organization revised of definition of extensive drug-resistant tuberculosis. We aimed to determine treatment outcomes of individuals affected by extensively drug-resistant tuberculosis in Europe. Methods: This observational, retrospective cohort study included patients diagnosed with extensively drug-resistant tuberculosis in the World Health Organization European Region from 2017 to 2023. Participating centres collected consecutive, detailed individual data for extensively drug-resistant tuberculosis patients. Data were analysed with meta- and regression methods, accounting for between-country heterogeneity. Findings: Among 11,003 patients with multidrug-resistant/rifampicin-resistant tuberculosis, 188 (1·7%) from 16 countries had extensively drug-resistant tuberculosis. Of these, 48·4% harboured strains with resistance to bedaquiline (n = 91/188), 34·0% to linezolid (n = 64/188), and 17·6% to both (n = 33/188). The individual composition of anti-tuberculosis regimens was highly variable, with 151 different drug combinations. Among the 156/188 (83·0%) patients with available treatment outcomes, the pooled percentage of successful outcomes was 40·2% (95% confidence interval [95% CI] 28·4%-53·2%). In patients with unsuccessful treatment outcomes (101/156), most experienced treatment failure (n = 57/156 [pooled proportion 37·1%], 95% CI: 26·1%-49·7%) or death (n = 30/156 [pooled proportion 21·3%], 95% CI: 15·7%-28·2%). After adjustment for disease severity, each additional likely effective drug decreased the odds of unsuccessful outcomes (adjusted odds ratio: 0·65, 95% CI: 0·45-0·96) (p = 0·026), whereas being treated in an upper-middle-income country increased the odds of unsuccessful outcomes compared with being treated in a high-income country (adjusted odds ratio: 13·7, 95% CI: 3·7-50·2) (p < 0·001). Compared with other levels of drug resistance, treatment outcomes were significantly worse for extensively drug-resistant tuberculosis. Interpretation: Only four out of ten patients affected by extensively drug-resistant tuberculosis achieved successful treatment outcomes. These findings highlight the need for adequate, individualised treatment regimens and optimised drug susceptibility testing. Funding: None.