Multidrug-Resistant Tuberculosis in Europe, 2010–2011

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Abstract

Ongoing transmission, high levels of drug resistance, and poor diagnostic

Abstract

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.

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National survey of drug-resistant tuberculosis in China.

Yanlin Zhao, Shaofa Xu, Lixia Wang … (2012)

The available information on the epidemic of drug-resistant tuberculosis in China is based on local or regional surveys. In 2007, we carried out a national survey of drug-resistant tuberculosis in China. We estimated the proportion of tuberculosis cases in China that were resistant to drugs by means of cluster-randomized sampling of tuberculosis cases in the public health system and testing for resistance to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and streptomycin and the second-line drugs ofloxacin and kanamycin. We used the results from this survey and published estimates of the incidence of tuberculosis to estimate the incidence of drug-resistant tuberculosis. Information from patient interviews was used to identify factors linked to drug resistance. Among 3037 patients with new cases of tuberculosis and 892 with previously treated cases, 5.7% (95% confidence interval [CI], 4.5 to 7.0) and 25.6% (95% CI, 21.5 to 29.8), respectively, had multidrug-resistant (MDR) tuberculosis (defined as disease that was resistant to at least isoniazid and rifampin). Among all patients with tuberculosis, approximately 1 of 4 had disease that was resistant to isoniazid, rifampin, or both, and 1 of 10 had MDR tuberculosis. Approximately 8% of the patients with MDR tuberculosis had extensively drug-resistant (XDR) tuberculosis (defined as disease that was resistant to at least isoniazid, rifampin, ofloxacin, and kanamycin). In 2007, there were 110,000 incident cases (95% CI, 97,000 to 130,000) of MDR tuberculosis and 8200 incident cases (95% CI, 7200 to 9700) of XDR tuberculosis. Most cases of MDR and XDR tuberculosis resulted from primary transmission. Patients with multiple previous treatments who had received their last treatment in a tuberculosis hospital had the highest risk of MDR tuberculosis (adjusted odds ratio, 13.3; 95% CI, 3.9 to 46.0). Among 226 previously treated patients with MDR tuberculosis, 43.8% had not completed their last treatment; most had been treated in the hospital system. Among those who had completed treatment, tuberculosis developed again in most of the patients after their treatment in the public health system. China has a serious epidemic of drug-resistant tuberculosis. MDR tuberculosis is linked to inadequate treatment in both the public health system and the hospital system, especially tuberculosis hospitals; however, primary transmission accounts for most cases. (Funded by the Chinese Ministry of Health.).

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Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes.

Rosella Centis, Kathryn DeRiemer, Dick Menzies … (2013)

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable drugs on treatment outcome. Compared with treatment failure, relapse and death, treatment success was higher in MDR-TB patients infected with strains without additional resistance (n=4763; 64%, 95% CI 57-72%) or with resistance to second-line injectable drugs only (n=1130; 56%, 95% CI 45-66%), than in those having resistance to fluoroquinolones alone (n=426; 48%, 95% CI 36-60%) or to fluoroquinolones plus second-line injectable drugs (extensively drug resistant (XDR)-TB) (n=405; 40%, 95% CI 27-53%). In XDR-TB patients, treatment success was highest if at least six drugs were used in the intensive phase (adjusted OR 4.9, 95% CI 1.4-16.6; reference fewer than three drugs) and four in the continuation phase (OR 6.1, 95% CI 1.4-26.3). The odds of success in XDR-TB patients was maximised when the intensive phase reached 6.6-9.0 months duration and the total duration of treatment 20.1-25.0 months. In XDR-TB patients, regimens containing more drugs than those recommended in MDR-TB but given for a similar duration were associated with the highest odds of success. All data were from observational studies and methodologies varied between centres, therefore, the bias may be substantial. Better quality evidence is needed to optimise regimens.

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Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis.

Carole D Mitnick, Susan K. Jacobson, M. Murray … (2010)

. The treatment of extensively drug-resistant tuberculosis (XDR TB) presents a major challenge. Second-line antimycobacterial drugs are less effective, more toxic, and more costly than first-line agents, and XDR TB strains are, by definition, resistant to the most potent second-line options: the injectable agents and fluoroquinolones. We conducted a meta-analysis to assess XDR TB treatment outcomes and to identify therapeutic approaches associated with favorable responses. We searched PubMed and EMBASE databases to identify studies conducted through May 2009 that report XDR TB treatment outcomes. The search yielded 13 observational studies covering 560 patients, of whom 43.7% (95% confidence interval, 32.8%-54.5%) experienced favorable outcomes, defined as either cure or treatment completion, and 20.8% (95% confidence interval, 14.2%-27.3%) died. Random effects meta-analysis and meta-regression showed that studies in which a higher proportion of patients received a later-generation fluoroquinolone reported a higher proportion of favorable treatment outcomes (P=.012). This meta-analysis provides the first empirical evidence that the use of later-generation fluoroquinolones for the treatment of XDR TB significantly improves treatment outcomes, even though drug-susceptibility testing demonstrates resistance to a representative fluoroquinolone. These results suggest that the addition of later-generation fluoroquinolones to XDR TB regimens may improve treatment outcomes and should be systematically evaluated in well-designed clinical studies.

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Author and article information

Journal

Journal ID (nlm-ta): Emerg Infect Dis

Journal ID (iso-abbrev): Emerging Infect. Dis

Journal ID (publisher-id): EID

Title: Emerging Infectious Diseases

Publisher: Centers for Disease Control and Prevention

ISSN (Print): 1080-6040

ISSN (Electronic): 1080-6059

Publication date (Print): March 2015

Volume: 21

Issue: 3

Pages: 409-416

Affiliations

[1]University of Namibia School of Medicine, Windhoek, Namibia (G. Günther, C. Lange);

[2]German Center for Infection Research, Research Center Borstel, Borstel, Germany (G. Günther, C. Lange);

[3] University of Amsterdam, Amsterdam, the Netherlands (F. van Leth);

[4]Institute of Phthisiopneumology, Chisinau, Moldova (S. Alexandru, A. Ciubanu, V. Crudu);

[5]Hospital Universitari Vall d’Hebron, Barcelona, Spain (N. Altet);

[6]Jordi Gol University, Barcelona (N. Altet);

[7]Asklepios Klinik Gauting, Gauting, Germany (K. Avsar);

[8]Statens Serum Institut, Copenhagen, Denmark (D. Bang);

[9]Herlev Hospital, Herlev, Denmark (D. Bang);

[10]Balti Municipal Hospital, Balti, Moldova (R. Barbuta);

[11]Homerton University Hospital, London, UK (G. Bothamley);

[12]National TB Reference Laboratory, Chisinau, Moldova (V. Crudu);

[13]Tartu University Lung Hospital, Tartu, Estonia (M. Danilovits);

[14]University of Warwick, Coventry, UK (M. Dedicoat);

[15]Heart of England Foundation Trust, Birmingham, UK (M. Dedicoat, H. Kunst);

[16]Vila Nova de Gaia/Espinho Medical School, Vila Nova de Gaia, Portugal (R. Duarte);

[17]Porto University, Porto, Portugal (R. Duarte);

[18]National Institute for Infectious Diseases L. Spallanzani, Rome, Italy (G. Gualano);

[19]Queen Mary University, London (H. Kunst);

[20]University Medical Center Groningen, Groningen, the Netherlands (W. de Lange);

[21]Riga East University Hospital, Riga, Latvia (V. Leimane);

[22]Radboud University Medical Centre, Nijmegen/Groesbeek, the Netherlands (C. Magis-Escurra);

[23]St. James's Hospital, Dublin, Ireland (A.-M. McLaughlin);

[24]University Medical Center St. Pieter, Brussels, Belgium (I. Muylle);

[25]Thomayer University Hospital, Prague, Czech Republic (V. Polcavá);

[26]Galliera Hospital, Genoa, Italy (E. Pontali);

[27]Marius-Nasta-Institut, Bucharest, Romania (C. Popa, V. Spinu);

[28]Otto Wagner Hospital, Vienna, Austria (R. Rumetshofer);

[29]Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Belarus (A. Skrahina, Varvara Solodovnikova);

[30]Azienda Ospedaliera della Valtellina e della Valchiavenna E. Morelli Reference Hospital for MDR and HIV-TB, Sondalo, Italy (S. Tiberi);

[31]Barts Health National Health Service Trust, London (S. Tiberi);

[32]National Institute for Health Development, Tallinn, Estonia, (P. Viiklepp);

[33]Karolinska Institute, Stockholm, Sweden (C. Lange)

Author notes

Address for correspondence: Christoph Lange, Clinical Tuberculosis Unit, Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center Borstel, Parkallee 35, 23845 Borstel, Germany; email: clange@ 123456fz-borstel.de

Article

Publisher ID: 14-1343

DOI: 10.3201/eid2103.141343

PMC ID: 4344280

PubMed ID: 25693485

SO-VID: 51d87bda-95bb-4102-b8bc-fbcac548d670

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Multidrug-Resistant Tuberculosis in Europe, 2010–2011

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Point-Of-Care Testing for Tuberculosis

Most cited references 16

National survey of drug-resistant tuberculosis in China.

Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes.

Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis.

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Cited by 32

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