Multidrug-resistant mycobacterium tuberculosis caused by the Beijing genotype and a specific T1 genotype clone [SIT no. 266] is widely transmitted in minsk

This study was performed in the city of Minsk in Belarus, where a very severe problem with MDR-TB was demonstrated in a recent drug resistant survey. The aim of this study was to use molecular typing of MDR and pan-susceptible clinical isolates of Mycobacterium tuberculosis to increase the understanding of the transmission patterns and possible differences between the strains causing susceptible and drug-resistant tuberculosis. Study population and methods Consecutive isolates from pulmonary TB patients in Minsk were collected at the Belarusian National Reference Laboratory. Isolates found to be either pan-susceptible or MDR were included in the study, which totally comprised 81 MDR and 82 pan-susceptible clinical isolates. All isolates were characterized by spoligotyping. The major clusters were characterized using sequencing of the pncA gene. Three out of four MDR cases were caused by one out of two drug-resistant clones of M. tuberculosis belonging to the Beijing and T1 genotypes, respectively. A single T1 clone, SIT No. 266, found exclusively in the MDR cohort, was shown to cause no less than 30% of all MDR-TB cases. Discussion: The findings indicate that the major cause of MDR-TB in Minsk is an ongoing transmission of certain already resistant M. tuberculosis strains. The significant transmission of MDR-TB in Minsk underlines the urgent need for strengthened infection control measures to limit the transmission in order to better control MDR-TB

Tentative susceptibility testing breakpoint for the neuroleptic drug thioridazine, a treatment option for multiband extensively drug resistant tuberculosis

New drugs against multi-[MDR] and extensively drug [XDR] resistant tuberculosis are urgently needed. While new candidate drugs are being developed, reinvestigation of already approved drugs available for other indications could be of value. The objective of this study is to determine tentative drug susceptibility testing strategies and breakpoints for thioridazine, a well-known and well-tolerated neuroleptic drug, which has been shown to be effective against drug resistant tuberculosis both in vitro and in vivo. By testing the minimal inhibitory concentration [MIC] on Middlebrook 7H10 media, the wild-type distribution of thioridazine was established for Mycobacterium tuberculosis [n = 51] and this distribution was compared to the MICs of M/XDR strains [n = 67]. A tentative epidemiological cut off [ECOFF] of thioridazine at 16 mg/L was suggested. Even though such concentrations are not clinically achievable in serum, thioridazine is concentrated intracellularly and concentrations of only 0.1 mg/L has been shown to kill M. tuberculosis residing inside cells. MICs above the wild-type [MIC > 16 mg/L] were found in 4/67 [6%] of the M/XDR strains suggesting that resistance mechanisms against thioridazine may already be present in resistant clinical strains. In view of the difficulties obtaining clinical outcome data for single drugs in the case of tuberculosis since combination therapy is mandatory, the tentative ECOFF may be considered a tentative clinical breakpoint, but the findings should be validated by others. The data from this study strengthens the use of thioridazine as a treatment option for M/XDR tuberculosis, although its proper place in the therapeutic arsenal should ideally be confirmed in clinical trials.