Thioridazine is cheap, and it inhibits the replication of all encountered Mtb strains regardless of their antibiotic resistance status , it enhances intracellular killing of MDR Mtb and XDR Mtb , it cures the mouse of a pulmonary Mtb infection and it has cured 17 XDR TB patients without producing any serious side effects . So why has it not been seriously considered and used now for therapy of problematic TB infections that cannot be readily cured with other available drugs especially in countries where MDR, XDR TB and now TDR TB infections are present in huge numbers? I welcome your thoughts and involvement.
References that discusses all of the above:
Amaral L, Boeree M, Gillespie SH, Udwadia Z, van Soolingen D. Editorial: Thioridazine cures XDR TB: The need for Global Clinical Trials For therapy of XDR TB is now. Int J Antimicrob Agents 2010; 35:524-526.
Amaral L, Udwadia Z, Abbate E and van Soolingen D. The added effect of Thioridazine in treatment of resistant TB. Int J Tuberculosis and Lung Disease. 2012;16:1706-1708.
Any ray of hope would get excellant acclaim to dwarf the ghost of mdrtb.it will be laudable to find thioridazine finding its place in combination with other second line drugs to beat menace of ....pan drug resistance.it will be respite to patients primarily and doctors too. But i have few doubts in my mind. No single drug will ever eradicate tb in any form.we have find new combinations and try to decipher forgotten antibiotics who may have antitubercular activity like clofazamine, thioacetazone, dapsone etc. In addition we may need to highlight anti tubercular activity of antifungals....
Dear Ajaz, Thioridazine activates the killing of intracellular Mtb by non-killing macrophages as those that are in the alveoli of the lung. Hence, it bypasses any response of the bug such as mutation, etc. Because it inhibits the efflux pump of mdr, xdr Mtb and because thioridazine is concentrated by the phagolysosome where Mtb is trapped, the concentrations reached are equivalent to those that are bactericidal. All of this means that Thioridazine when used in combo with antibiotics to which the bug was initially resistant, affords the use of old antibiotics that have fallen by the wayside due to the advent of mdr, etc.. This is why it has now been shown to cure XDR TB patients in combo with antibiotics to which the infecting strains was initially resistant.
You must also note that because no one can make money with thioridazine given that it is no longer patent protected, interest .........
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