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Clinical and operational value of the extensively drug-resistant tuberculosis definition

¹ WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, ² E. Morelli Hospital, Reference Hospital for MDR and HIV TB, Sondalo, ³ National Institute for Infectious Diseases L. Spallanzani, Rome, ⁶ Fondazione S. Maugeri, Care and Research Institute, Cassano delle Murge, ⁷ University of Perugia, Internal Medicine, Section of Respiratory Diseases, Perugia, ⁸ Supranational Reference Laboratory, S. Raffaele Institute, ⁹ San Paolo Hospital, University of Milan, and ¹¹ TB Reference Centre, Villa Marelli Institute, Niguarda Hospital, Milan, and ¹⁰ University of Brescia, Brescia, Italy., ⁴ University of Tartu, Tartu, Estonia., ⁵ Division of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, Borstel, Germany. ¹² Stop TB Dept, World Health Organization, Geneva, Switzerland.

CORRESPONDENCE: G. B. Migliori, WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, via Roncaccio 16, 21049, Tradate, Italy. Fax: 39 331829402. E-mail: gbmigliori{at}fsm.it

Keywords: Clinical value, drug resistance, extensively drug-resistant tuberculosis, multidrug-resistant tuberculosis, tuberculosis

Received: June 25, 2007
Accepted July 23, 2007

Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs.

To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999–2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites.

Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB).

The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.

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