Multidrug-resistant TB in Eastern region of the EU: is the shorter regimen an exception or a rule?

WHO recently recommended the use of a shorter multidrug-resistant TB (MDR-TB) regimen under programmatic conditions. We assessed eligibility for this regimen in a cohort of 737 adult patients with MDR-TB from Latvia, Lithuania, Estonia and Bucharest city recruited in 2007 and 2009. Only 4.2% of the patients were eligible for this regimen. Ethambutol (64%), pyrazinamide resistance (58%) and previous exposure to second-line TB drugs were major reasons for non-eligibility. High-level resistance to isoniazid is expected due to widespread prevalence of katG mutations. In Eastern Europe, the use of the shorter regimen might be an exception rather than a rule.

Survival of patients with multidrug-resistant TB in Eastern Europe: what makes a difference?

BACKGROUND: The quality of care for patients with TB in Eastern Europe has improved significantly; nevertheless drug resistance rates remain high. We analysed survival in a cohort of patients with multidrug-resistant and extensively drug-resistant (MDR-/XDR-) TB from Latvia, Lithuania, Estonia and Bucharest city. METHODS: Consecutive adult new and retreatment patients with culture-confirmed pulmonary MDR-TB registered for treatment in 2009 (and in 2007 in Latvia) were enrolled; prospective survival information was collected. RESULTS: A total of 737 patients were included into the cohort. Of all MDR-TB cases, 46% were newly diagnosed; 56% of all MDR-TB cases had no additional resistance to fluoroquinolones or injectable agents, 33% had pre-XDR-TB and 11% XDR-TB. Median survival was 5.9 years in patients with MDR-TB and XDR-TB; 1.9 years in patients coinfected with HIV. Older age, male gender, alcohol abuse, retirement, co-morbidities, extrapulmonary involvement and HIV coinfection independently worsened survival. Inclusion of fluoroquinolones and injectable agents improves survival in patients with MDR-TB. Pre-XDR and XDR status did not significantly shorten survival as long as fluoroquinolones and injectable agents were part of the regimen. Moxifloxacin seems to improve survival in ofloxacin-susceptible patients when compared with older generation fluoroquinolones. CONCLUSIONS: The burden of additional resistances in patients with MDR-TB is high likely due to primary transmission of resistant strains. Social and programmatic factors including management of alcohol dependency, expansion of HIV testing and antiretroviral treatment need to be addressed in order to achieve cure and to interrupt transmission. The role of last generation fluoroquinolones and injectable agents in treatment of patients with pre-XDR and XDR-TB needs to be further investigated.

Resistance profile and risk factors of drug resistant tuberculosis in the Baltic countries.

The rates of multi- and extensively drug-resistant tuberculosis (X/MDRTB) in the Baltic countries are the highest within the European Union hampering recent achievements of national TB control programmes. We included all consecutive culture-confirmed X/MDRTB patients registered for treatment in 2009 in Latvia, Lithuania and Estonia into this multicenter case-control study. Cases were compared with randomly selected controls with non-MDRTB registered for treatment in the same year across these sites. Of 495 MDRTB patients, 243 (49.7%) showed resistance to at least one second-line drug, 206 (42.1%) had pre-XDRTB (i.e. MDRTB with additional resistance to a second-line injectable or fluoroquinolones) and 64 (13.1%) had XDRTB. Younger age, male gender and known contact with an MDRTB case were associated with increased risk of primary infection with X/MDRTB strains. Previous treatment and alcohol abuse were strong predictors for MDRTB acquisition; defaults and failures in the past triggered XDRTB development. All patients received appropriate therapy; less than half of the patients were fully adherent. An erroneous treatment strategy is unlikely to drive resistance development. Increasing patients' compliance, addressing issues of social support, rapid detection of drug resistance and improving infection control is crucial for prevention of further spread of X/MDRTB and achieving higher cure rates.

Survival of drug resistant tuberculosis patients in Lithuania: retrospective national cohort study.

Objective To establish risk factors influencing survival of patients with multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDRTB). Design All MDR/XDRTB cases (n=1809) reported from 2002 to 2008 in Lithuania with a known outcome were included in the survival analysis. Results Median survival for MDRTB and XDRTB patients was 4.1 (95% CI 3.7 to 4.4) and 2.9 (95% CI 2.2 to 3.9) years. In a multivariable analysis adjusting for other patient characteristics, the difference in survival between MDRTB and XDRTB patients was not significant (HR=1.29 (0.91 to 1.81)). Older age (HR=4.80 (3.16 to 7.29)) for 60+ vs <30 years, rural living (HR=1.20 (1.02 to 1.40)), alcohol use (HR=1.49 (1.13 to 1.96)) for alcoholic versus moderate use, unemployment (HR=1.79 (1.31 to 2.46)), lower education levels (HR=1.50 (1.08 to 2.07)) for primary level versus tertiary level, cavitary disease (HR=1.54 (1.29 to 1.83)) and being smear positive at the time of MDR/XDRTB diagnosis (HR=1.47 (1.19 to 1.82)) were associated with poorer survival. HIV positivity significantly affected survival (HR=3.44 (1.92 to 6.19)) for HIV positive versus HIV negative; HR=1.60 (1.28 to 2.01) for HIV not tested versus HIV negative). There was no difference in survival of patients who acquired MDR/XDRTB during treatment compared with patients with primary MDR/XDRTB (HR=1.01 (0.85 to 1.19)). Treatment with a second-line drug improved survival (HR=0.40 (0.34 to 0.47)). In a subgroup with genotyped TB strains, a Beijing family of strains was associated with poorer survival (HR=1.71 (1.19 to 2.47)). Conclusions Social factors, rural living, HIV infection and Beijing strain family impact on survival. Survival of MDR/XDRTB patients is short. Rapid drug resistance identification, early administration of appropriate treatment and achieving high cure rates, expansion of HIV testing and antiretroviral treatment are necessary for optimal management of MDR/XDRTB.