Gunar Günther1,2, Frank van Leth3,4, Sofia Alexandru5, Neus Altet6, Korkut Avsar7, Didi Bang8, Raisa Barbuta9, Graham Bothamley10, Ana Ciobanu5, Valeriu Crudu5,11, Manfred Danilovits12, Martin Dedicoat13,14, Raquel Duarte15,16, Gina Gualano17, Heinke Kunst18, Wiel de Lange19, Vaira Leimane20, Anne-Marie McLaughlin21, Cecile Magis-Escurra22, Inge Muylle23, Veronika Polcová24, Cristina Popa25, Rudolf Rumetshofer26, Alena Skrahina27, Varvara Solodovnikova27, Victor Spinu25, Simon Tiberi28,29, Piret Viiklepp30, Christoph Lange1,31,32,33. 1. 1 Research Center Borstel, Clinical Infectious Diseases, German Center for Infection Research, Borstel, Germany. 2. 2 Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia. 3. 3 Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. 4. 4 Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands. 5. 5 Institute of Phthisiopneumology, Chisinau, Republic of Moldova. 6. 6 Hospital Universitari Vall d'Hebron, Research Institute-IDIAP Jordi Gol, Barcelona, Spain. 7. 7 Asklepios Klinik Gauting, Gauting, Germany. 8. 8 Statens Serum Institut, Copenhagen, Denmark. 9. 9 Balti Municipal Hospital, Balti, Republic of Moldova. 10. 10 Homerton University Hospital, London, United Kingdom. 11. 11 National Tuberculosis Reference Laboratory, Chisinau, Republic of Moldova. 12. 12 Tartu University Lung Hospital, Tartu, Estonia. 13. 13 Heart of England Foundation Trust, Birmingham, United Kingdom. 14. 14 University of Warwick, Coventry, United Kingdom. 15. 15 EpiUnit, Institute of Public Health, Porto University, Porto, Portugal. 16. 16 Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal. 17. 17 National Institute for Infectious Diseases "L, Spallanzani," Rome, Italy. 18. 18 Queen Mary University, London, United Kingdom. 19. 19 University of Groningen, University Medical Center Groningen, Tuberculosis Centre Beatrixoord, Haren, the Netherlands. 20. 20 Riga East University Hospital, Tuberculosis and Lung Diseases Centre, Riga, Latvia. 21. 21 St. James's Hospital, Dublin, Ireland. 22. 22 Radboud University Medical Centre-TB Expert Centre UCCZ Dekkerswald, Nijmegen-Groesbeek, the Netherlands. 23. 23 University Medical Center St. Pieter, Brussels, Belgium. 24. 24 Thomayer University Hospital, Prague, Czech Republic. 25. 25 Marius-Nasta-Institut, Bucharest, Romania. 26. 26 Otto Wagner Hospital, Vienna, Austria. 27. 27 Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus. 28. 28 Ospedale Eugenio Morelli Reference Hospital for MDR and HIV-TB, Sondalo, Italy. 29. 29 Barts Health NHS Trust, London, United Kingdom. 30. 30 National Institute for Health Development, Tallinn, Estonia. 31. 31 International Health/Infectious Diseases, University of Lübeck, Lübeck, Germany. 32. 32 Department of Medicine, Karolinska Institute, Stockholm, Sweden; and. 33. 33 German Center for Infection Research, Borstel, Germany.
Abstract
RATIONALE: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower. OBJECTIVES: To document the management and treatment outcome in patients with MDR-TB in Europe. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET). MEASUREMENTS AND MAIN RESULTS: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%). CONCLUSIONS: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.
RATIONALE: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower. OBJECTIVES: To document the management and treatment outcome in patients with MDR-TB in Europe. METHODS: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET). MEASUREMENTS AND MAIN RESULTS: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%). CONCLUSIONS: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.
Authors: Ivan S Pradipta; Natasha Van't Boveneind-Vrubleuskaya; Onno W Akkerman; Jan-Willem C Alffenaar; Eelko Hak Journal: Antimicrob Resist Infect Control Date: 2019-07-12 Impact factor: 4.887
Authors: Helen Cox; Galo A Goig; Zubeida Salaam-Dreyer; Anzaan Dippenaar; Anja Reuter; Erika Mohr-Holland; Johnny Daniels; Patrick G T Cudahy; Mark P Nicol; Sonia Borrell; Miriam Reinhard; Anna Doetsch; Christian Beisel; Sebastien Gagneux; Robin M Warren; Jennifer Furin Journal: J Clin Microbiol Date: 2022-03-16 Impact factor: 5.948
Authors: Le Hong Van; Phan Trieu Phu; Dao Nguyen Vinh; Vo Thanh Son; Nguyen Thi Hanh; Le Thanh Hoang Nhat; Nguyen Huu Lan; Truong Van Vinh; Nguyen Thi Mai Trang; Dang Thi Minh Ha; Guy E Thwaites; Nguyen Thuy Thuong Thuong Journal: BMC Infect Dis Date: 2020-02-22 Impact factor: 3.090