MDR-TB Treatment & Prevention
Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study
In this study, we describe the treatment, management, and outcomes of patients with extensively drug-resistant tuberculosis (XDR-TB) in Tomsk, Russia.
We undertook a retrospective cohort study of 608 patients with multi drug resistant TB (MDR TB) who had treatment in civilian or prison services between Sept 10, 2000, and Nov 1, 2004, according to the treatment strategy recommended by the WHO.
All patients received the highest doses of second-line antituberculosis medications that they could tolerate in regimens formulated by use of the algorithm described by Mukherjee and colleagues: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)15496-2/ful.... Tomsk patients did not receive third-line antituberculosis drugs such as clofazimine or linezolid.
4.8% (29) of the total patients in the cohort had baseline XDR TB, and treatment failure was more common in them. The small number of patients with XDR-TB in our report constrained our ability to examine associations between doses, efficacy, and adverse events. Despite this, we did see that the overall incidence of adverse events was not higher among XDR-TB patients, and we do not have strong clinical reasons to suspect that it would be.
Complementing this paper and following feedback from correspondence published in The Lancet (Deepak Aggarwal and colleagues: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61949-2/ful...
Jussara Silva and colleagues: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61950-9/ful...), you may also want to read details of antituberculosis regimens, including doses but not adverse events, as laid out by Mitnick and colleagues in the appendix of this August 2008 NEJM paper: Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis (available here: http://www.ghdonline.org/drtb/resource/comprehensive-treatment-of-extensively...).
Re: the question of the ideal drugs to use for XDR-TB patients, one study in human beings: Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis, published in The International Journal of Tuberculosis and Lung Disease in June 2006 (full text available here: http://www.ingentaconnect.com/content/iuatld/ijtld/2006/00000010/00000006/art...) suggests that later-generation fluoroquinolones have greater antituberculosis activity than earlier ones; this improvement might contribute to better outcomes.
Furthermore, questions about the best drug combinations and doses for XDR-TB highlight the urgent need for clinical trials to optimize current treatment approaches. Indeed, scientists and activists have called attention to this need with The Cambridge Declaration: towards clinical trials for drug-resistant tuberculosis, Cambridge, MA, USA (http://www.ghdonline.org/drtb/resource/the-cambridge-declaration-towards-clin...).
Regarding the crucial question of whether treatment duration itself should be regarded as an exposure variable in the multivariable model used in our analysis (as raised by Jussara Silva and colleagues), and although the shorter treatment duration in XDR-TB patients was a notable finding, we felt that it was more likely to be a consequence of poor clinical response and not a contributing factor to poor outcome.
Tomsk physicians weighed up public-health considerations and the likelihood of treatment response, and only stopped treatment when they felt that the patient had clinically declared himself or herself as a treatment failure. Treatment was discontinued well after the median culture conversion time to avoid unnecessary toxic effects and the potential for selection of pan-resistant strains.
We conclude that use of aggressive second-line antituberculosis treatment regimens from the outset—with proper management of adverse events—can lead to positive outcomes in a significant proportion of patients. Treatment duration is another timely question that requires rigorous examination through clinical trials.
Attached resource:
