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Ahead of Print -Multidrug-Resistant Tuberculosis in Europe, 2010–2011 - Volume 21, Number 3—March 2015 - Emerging Infectious Disease journal - CDC

Ahead of Print -Multidrug-Resistant Tuberculosis in Europe, 2010–2011 - Volume 21, Number 3—March 2015 - Emerging Infectious Disease journal - CDC

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Thumbnail of TBNET study sites in the Pan European network for study and clinical management of drug- resistant tuberculosis (TBPAN-NET) project. Stratification is based on the incidence of tuberculosis (TB) reported during 2010–2011, which matched the inclusion period of the study. Data for 2011 were obtained from the European Centre for Disease Control and Prevention (10). Low TB incidence, <20 cases/100,000 persons; intermediate TB incidence, 20–100 cases/100,000 persons; high TB incidence

Figure. TBNET study sites in the Pan European network for study and clinical management of drug- resistant tuberculosis (TBPAN-NET) project. Stratification is based on the incidence of tuberculosis (TB) reported during 2010–2011,...

Volume 21, Number 3—March 2015


Multidrug-Resistant Tuberculosis in Europe, 2010–2011


Technical Appendicies


Gunar Günther, Frank van Leth, Sofia Alexandru, Neus Altet, Korkut Avsar, Didi Bang, Raisa Barbuta, Graham Bothamley, Ana Ciobanu, Valeriu Crudu, Manfred Davilovits, Martin Dedicoat, Raquel Duarte, Gina Gualano, Heinke Kunst, Wiel de Lange, Vaira Leimane, Cecile Magis-Escurra, Anne-Marie McLaughlin, Inge Muylle, Veronika Polcová, Emanuele Pontali, Christina Popa, Rudolf Rumetshofer, Alena Skrahina, Varvara Solodovnikova, Victor Spinu, Simon Tiberi, Piret Viiklepp, Christoph LangeComments to Author , and TBNET
Author affiliations: University of Namibia School of Medicine, Windhoek, Namibia (G. Günther, C. Lange);Research Center Borstel, Borstel, Germany (G. Günther, C. Lange)University of Amsterdam, Amsterdam, the Netherlands (F. van Leth)Institute of Phthisiopneumology, Chisinau, Moldova (S. Alexandru, A. Ciubanu, V. Crudu)Hospital Universitari Vall d’Hebron, Barcelona, Spain (N. Altet)Jordi Gol University, Barcelona (N. Altet)Asklepios Klinik Gauting, Gauting, Germany (K. Avsar)Statens Serum Institut, Copenhagen, Denmark (D. Bang)Herlev Hospital, Herlev, Denmark (D. Bang)Balti Municipal Hospital, Balti, Moldova (R. Barbuta);Homerton University Hospital, London, UK (G. Bothamley)National TB Reference Laboratory, Chisinau, Moldova (V. Crudu)Tartu University Lung Hospital, Tartu, Estonia (M. Danilovits)University of Warwick, Coventry, UK (M. Dedicoat)Heart of England Foundation Trust, Birmingham, UK (M. Dedicoat, H. Kunst)Vila Nova de Gaia/Espinho Medical School, Vila Nova de Gaia, Portugal (R. Duarte)Porto University, Porto, Portugal (R. Duarte)National Institute for Infectious Diseases L. Spallanzani, Rome, Italy (G. Gualano)Queen Mary University, London (H. Kunst)University Medical Center Groningen, Groningen, the Netherlands (W. de Lange);Riga East University Hospital, Riga, Latvia (V. Leimane)Radboud University Medical Centre, Nijmegen/Groesbeek, the Netherlands (C. Magis-Escurra)St. James's Hospital, Dublin, Ireland (A.-M. McLaughlin)University Medical Center St. Pieter, Brussels, Belgium (I. Muylle)Thomayer University Hospital, Prague, Czech Republic (V. Polcavá)Galliera Hospital, Genoa, Italy (E. Pontali)Marius-Nasta-Institut, Bucharest, Romania (C. Popa, V. Spinu)Otto Wagner Hospital, Vienna, Austria (R. Rumetshofer)Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus (A. Skrahina, Varvara Solodovnikova);Azienda Ospedaliera della Valtellina e della Valchiavenna E. Morelli Reference Hospital for MDR and HIV-TB, Sondalo, Italy (S. Tiberi)Barts Health National Health Service Trust, London (S. Tiberi)National Institute for Health Development, Tallinn, Estonia, (P. Viiklepp)Karolinska Institute, Stockholm, Sweden (C. Lange)


Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non–MDR TB were enrolled at 23 centers in 16 countries in Europe during 2010–2011. A total of 52.4% of MDR TB patients had never been treated for TB, which suggests primary transmission of MDR M. tuberculosis. At initiation of treatment for MDR TB, 59.7% of M. tuberculosis strains tested were resistant to pyrazinamide, 51.1% were resistant to ≥1 second-line drug, 26.6% were resistant to second-line injectable drugs, 17.6% were resistant to fluoroquinolones, and 6.8% were extensively drug resistant. Previous treatment for TB was the strongest risk factor for MDR TB. High levels of primary transmission and advanced resistance to second-line drugs characterize MDR TB cases in Europe.
Emergence of drug-resistant tuberculosis (TB) threatens the goal of TB elimination (1). Multidrug-resistant (MDR) TB is defined by in vitro resistance ofMycobacterium tuberculosis to at least both of the 2 most effective drugs for treatment (rifampin and isoniazid). Extensively drug-resistant TB (XDR TB) is defined as MDR TB plus in vitro resistance to at least 1 second-line injectable drug (amikacin, capreomycin, or kanamycin) plus resistance to any of the fluoroquinolones (e.g., ofloxacin, levofloxacin, or moxifloxacin) (2). In the World Health Organization (WHO) European Region, the estimated incidence of patients with MDR TB differs markedly: 1.6 cases/100,000 persons in the 29 European Union/European Economic Area countries and 16.8 cases/100,000 persons in the 24 other countries of the region in 2012 (Technical Appendix[PDF - 147 KB - 6 pages] Table 1) (3). The actual number of patients with MDR TB living in this region may be much higher because a substantial proportion of patients are never screened for drug-resistant TB before starting treatment, partly because of a lack of diagnostic capacity (3).
MDR TB is associated with poor treatment outcomes (1,2,4). The proportion of treatment success in patients with MDR TB was only 54% in an individual patient data metaanalysis of >9,000 patients from 32 observational studies (5). Results from this cohort showed that additional resistance to fluoroquinolones in patients with MDR TB reduced treatment success to 48%; patients with XDR TB were treated successfully in 40% of cases (6), which approached treatment outcomes similar to those of the pre–antimicrobial drug era (4). A recent surveillance report from the EU reported 32.2% treatment success for MDR TB and 19.1% treatment success for XDR TB (7).
Detailed information about characteristics, management, and outcomes of patients with MDR TB in Europe is scarce but essential to inform health policy makers and optimize disease management (8). We compared baseline characteristics and risk factors for patients with MDR TB, as well as availability and results of drug susceptibility testing (DST) for second-line drugs for treatment of TB, in a cohort of patients from 16 countries in Europe with low, intermediate, and high incidence of TB, who had started first-line or second-line TB treatment.

Dr. Günther is a consultant physician and project manager of the TBNET MDR TB cohort at the Research Center Borstel, Borstel, Germany. His primary research interest is drug-resistant tuberculosis.


We thank Cordula Ehlers for providing excellent assistance.
Additional contributors from TBNET: Marcel Rowhani (Vienna, Austria); Vera Avchinko, Dzimitry Katovich, Dzimitri Klimuk, Valentina Lobik, Zoya Rohaya, Alexander Shirochyn (Minsk, Belarus); Jana Kotrbova, Martina Vasakova (Prague, Czech Republic); Aase Bengard Andersen (Copenhagen, Denmark); Nelleke Smitsman (Borstel, Germany); Ralf Mütterlein (Parsberg, Germany); Saverio de Lorenzo (Sondalo, Italy); Liga Rusmane (Riga, Latvia); Ana Donica, Ilie Cernenco (Chisinau, Moldavia); Vera Dubceac (Balti, Moldavia); Femke Cuppen, Inge de Guchtenaire (Nijmegen, the Netherlands); Robert Meesters, Mark te Pas, Bram Prins (Amsterdam, the Netherlands); Ana Atunes (Villa Nova de Gaia, Portugal); Dan Gainaru, Elmira Ibraim, Mirela Tigau (Bucharest, Romania); Juan Cayla, Laia Fina, Maria Luiza de Souza Galvao, José Maldonado (Barcelona, Spain).


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Technical Appendix

Suggested citation for this article: Günther G, van Leth F, Alexandru S, Altet N, Avsar K, Bang D, et al. Multidrug-resistant tuberculosis in Europe, 2010–2011. Emerg Infect Dis. 2015 Mar [date cited]. http://dx.doi.org/10.3201/eid2103.141343
DOI: 10.3201/eid2103.141343
1Additional contributors from TBNET are listed at the end of this article.

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