Mycobacterium tuberculosis that is resistant to
Isoniazid (INH) and
Rifampin (Rif) and hence, multi-
drug resistant (MDR) has progressed to extensive
drug resistant (XDR) status. XDR strains of Mycobacterium tuberculosis (XDR Mtb) are resistant, in addition to INH and Rif, to any
fluoroquinolone,
streptomycin and to any of the
injectable anti-TB drugs
kanamycin,
amikacin and
capreomycin.
Therapy of the
XDR TB patient, even under the best conditions, is problematic and at least 20% of
XDR TB patients die within one year after diagnosis. Mortality among
XDR TB patients co-infected with HIV or presenting with
AIDS is considerably higher reaching levels of 80% or higher. Drugs that are to prove effective against XDR Mtb must be able to reach the organism at the site where it mainly resides-the pulmonary macrophage. However, experience tells us that no matter how effective a
drug may be, it will be followed by resistance. We have been able to demonstrate that
thioridazine, a
neuroleptic in safe use for over forty years, enhances the killing of phagocytosed Mycobacterium tuberculosis regardless of its
antibiotic susceptibility profile and cure the mouse of a Mycobacterium tuberculosis pulmonary
infection. Most recently, others have employed our studies for the
therapy of the
XDR TB patient with
thioridazine and cured 10 out of 12
XDR TB patients of an XDR Mtb
infection. Although
thioridazine is beyond patent protection, its use for the
therapy of
XDR TB is new and therefore, a patent may be sought for "use as an anti-
XDR TB agent".