Interventions for Tuberculosis Control and Elimination 2002

ial agents was thus only natural. 1172-1174 However, the concentrations
needed to exert activity by far exceed what is achievable within the nontoxic
range. The argument for considering phenothiazines for the treatment
of tuberculosis stems from the fact that pulmonary macrophages concentrate
chlorpromazine (the first phenothiazine developed) 100-fold above
what is found in plasma, concentrations that are active against mycobacteria
in vitro 1172 and in vivo. 1175 Thioridazine, a well tolerated phenothiazine,
has been shown to be active against both susceptible and resistant tubercle
bacilli. 1176-1178 Chlorpromazine has a titrable ability to slow the growth of
intracellular tubercle bacilli in vitro. 1179 Phenothiazines have not yet been
tested for their activity against tuberculosis in humans.
Tuberactinomycin
Tuberactinomycin, a polypeptide, was isolated in the Toyo Jozo research
laboratories in Japan from Streptomyces griseoverticullatus var. tuberacticus
in 1966. 1180 and was shown to be active against both kanamycin-susceptible
and -resistant strains. 1181,1182 Tuberactinomycin-N was semisynthetically
derived from this compound and found to have stronger
antimycobacterial activity and to be associated with less ototoxicity. 1183,1184
Its use has been largely limited to East Asia, where it was found to be a
useful alternative to capreomycin in the treatment of multidrug-resistant,
aminoglycoside-resistant tuberculosis.
165