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

International Journal of Mycobacteriology
Kristian ÄngebyThomas Schön

Abstract

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 16mg/L was suggested. Even though such concentrations are not clinically achievable in serum, thioridazine is concentrated intracellularly and concentrations of only 0.1mg/L has been shown to kill M. tuberculosis residing inside cells. MICs above the wild-type (MIC>16mg/L) were found in 4/67 (6%) of the M/XDR strains suggesting that resistance mechanisms against thioridazine may already be present in resistant cl...Continue Reading

References

Apr 7, 2009·International Journal of Antimicrobial Agents·Jakko van IngenDick van Soolingen
Jul 28, 2009·The Journal of Antimicrobial Chemotherapy·Thomas SchönKristian A Angeby
Mar 15, 2011·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·T SchönK A Angeby
May 10, 2011·Recent Patents on Anti-infective Drug Discovery·Charles Sohaskey
Aug 30, 2011·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Liliana RodriguesMiguel Viveiros
Sep 18, 2012·Bulletin of the World Health Organization·Kristian ÄngebyThomas Schön

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