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

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.

Resistance of multidrug-resistant strains of Mycobacterium tuberculosis from the Archangel oblast, Russia, to second-line anti-tuberculosis drugs.

Multidrug-resistant tuberculosis has become common all over the world, necessitating the inclusion of second-line drugs in treatment regimens. In the present study, the susceptibility of a selection of multidrug-resistant strains of Mycobacterium tuberculosis isolated in the Archangel oblast, Russia, to second-line anti-tuberculosis drugs was analysed. Susceptibility testing of 77 Mycobacterium tuberculosis strains was performed by the Bactec method using the following recommended drug concentrations: capreomycin 1.25 microg/ml; ethionamide 1.25 microg/ml; kanamycin 5 microg/ml; and ofloxacin 2 microg/ml. The majority of strains (92.2%) were resistant to ethionamide. High rates of drug resistance were also found for capreomycin (42.9%) and kanamycin (41.6%), while nearly all strains (98.7%) were susceptible to ofloxacin. The high rates of resistance to ethionamide, capreomycin, and kanamycin show the real burden of drug resistance in the region and pose a serious problem for the treatment of patients with multidrug-resistant tuberculosis.

Impact of drug-resistant Mycobacterium tuberculosis on treatment outcome of culture-positive cases of tuberculosis in the Archangel oblast, Russia, in 1999.

The objective of this study was to evaluate the outcome of treatment of culture-positive cases of tuberculosis registered in Archangel, Russia, in 1999, and to analyse the influence of Mycobacterium tuberculosis drug resistance on treatment outcome. The outcome of tuberculosis treatment was evaluated for 235 new and 61 previously treated culture-positive cases diagnosed in 1999. Of the 235 new cases, there were 150 (63.8%) cases of treatment completion, 20 (8.5%) cases of treatment failure, 29 (12.3%) cases of death during treatment, and 29 (12.3%) cases in which the patient failed to pick up medications for at least 2 consecutive months. The outcome in 7 (3%) cases was unknown, as the patients were transferred outside the oblast region. Among the 61 previously treated cases, the rate of treatment completion was low (26.2%), and rates of treatment failure (23%) and failure to pick up medications for at least 2 consecutive months (29.5%) were high. The relation between the susceptibility pattern of the infecting strain as determined by the Bactec method and tuberculosis treatment outcome was analysed for 76 patients. The majority (69%) of patients infected with drug-susceptible strains was cured. A large proportion (58.8%) of patients infected with Mycobacterium tuberculosis resistant to more than two drugs did not respond to treatment, i.e. the treatment failed or the patients died. The high rates of death (16.7%) and failure (66.7%) among patients infected with multidrug-resistant strains illustrate the negative impact of multidrug resistance on the outcome of tuberculosis treatment. Pan-resistance was significantly associated with treatment failure (P<0.001). The spread of resistant Mycobacterium tuberculosis has a serious negative impact on the outcome of tuberculosis treatment in Archangel, Russia.