Foreword

Resurgence of tuberculosis (TB) worldwide, coupled to increasing frequency of TB infections that are multi-drug (MDR TB) and extensive drug resistant (XDR TB), infections that are problematic to treat, extol high human and financial costs. At the present time there are no new drugs that are effective against these antibiotic resistant infections. Therefore, there is an urgent need for effective agents that are safe and within economic means of indigent countries where these infections are predominant. This issue of PRI is dedicated to present reviews that support the use of the neuroleptic thioridazine (TZ) for therapy of MDR and XDR TB either as a salvage drug or in combination with antibiotics to which the patient was initially nonresponsive. and this may also be extended to non-tuberculous mycobacterial disease. The reviews provide up-to the minute perspective of the status of drug development for therapy of MDR and XDR TB infections (see SH Gillespie et al), current and future therapy of MDR and XDR TB infections (see M Boeree), the pharmacology of TZ (see HR Thanacoody), the use of TZ as a “salvage drug” for improving the quality of life and possible extension of life of the MDR and XDR TB patient presenting with a somber prognosis (see Z Udwadia), the successful therapy of 10 out of 12 XDR TB patients and protocols used (see Amaral et al.), the targeting of the human macrophage for enhanced killing of intracellular strains of MDR and XDR Mycobacterium tuberculosis by TZ and other agents that inhibit K+ and Ca++ efflux (see M Martins), the inhibition of efflux pumps that mediate MDR phenotypes of Mycobacterium tuberculosis by TZ and therefore reduce or reverse resistance to antibiotics to which the bacterium is initially resistant (see L Rodrigues et al.), the in vitro killing of mycobacteria (see-J van Ingen) and dormant mycobacteria by TZ-possibly suggestive of in vivo killing of latent mycobacteria of the infected patient (see C Sohaskey), the modulation of essential genes for survival of mycobacteria by TZ (see N Dutta et al.) and a revolutionary new method for the alteration of anti-bacterial activity of an agent subsequent to exposure to specific high energy lasers (see M Pascu et al.). All in all, the contents of this special issue provide the reader sufficient information regarding the role that TZ is to play in the therapy of MDR and XDR TB infections, for purposes of considering a variety of possibilities for patenting TZ as a “New Use ”. It is anticipated that as is usually the case, financial motivation will move TZ from its current status “potential anti-MDR/XDR agent,” to one that will cure MDR and XDR TB. Therefore, consideration for patenting possibilities may contribute significantly to the elimination of an infection that has plagued mankind since he left the cave and became a landed animal (farmer).