title: Clinical and operational value of the extensively drug-resistant tuberculosis definition.
abstract: 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.
authors: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S Maugeri, Care and Research Institute, via Roncaccio 16, 21049, Tradate, Italy. gbmigliori@fsm.it
authors: G B
authors: GB
authors: Migliori
authors: G
authors: G
authors: Besozzi
authors: E
authors: E
authors: Girardi
authors: K
authors: K
authors: Kliiman
authors: C
authors: C
authors: Lange
authors: O S
authors: OS
authors: Toungoussova
authors: G
authors: G
authors: Ferrara
authors: D M
authors: DM
authors: Cirillo
authors: A
authors: A
authors: Gori
authors: A
authors: A
authors: Matteelli
authors: A
authors: A
authors: Spanevello
authors: L R
authors: LR
authors: Codecasa
authors: M C
authors: MC
authors: Raviglione
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D003141:Communicable Diseases / Q000628:therapy; D018432:Drug Resistance, Multiple; D054908:Extensively Drug-Resistant Tuberculosis / Q000145:classification* / Q000175:diagnosis* / Q000453:epidemiology*; D014943:Global Health; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D011159:Population Surveillance; D011634:Public Health; D012293:Rifampin / Q000494:pharmacology*; D012306:Risk; D012426:Russia; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin