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

Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?

The excellent letter by HOLTZ and CEGIELSKI contributing to the current discussion on extensively drug-resistant (XDR)-tuberculosis (TB). Several publications have already demonstrated that resistance to fluoroquinolones (FQ) is independently associated with poor outcome and/or that the possibility of including FQ in regimens improves treatment outcomes of multidrug-resistant (MDR)-TB cases. This happened before the (recent) description of XDR-TB. We do not know how many of the patients with MDR-TB strains were, in fact, infected with XDR Mycobacterium tuberculosis. We wanted to establish the role of the different XDR-defining components (e.g. isoniazid and rifampicin, FQ and injectable second-line drugs) in determining poor treatment outcomes