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[Expectation of new antituberculous drugs and targeting therapy for treatment of mycobacterial infections].

Recent AIDS endemic causes the worldwide increase in intractable mycobacterial infections including extrapulmonary tuberculosis due to drug resistant organisms and disseminated Mycobacterium avium complex infections. Therefore, new antituberculous (antimycobacterial) drugs and development of regimens and protocols for clinical treatment of such mycobacterial infections are urgently needed. Here, I described the present situations of new antituberculous agents, in particular new rifamycin derivatives including rifabutin and benzoxazinorifamycin (KRM-1648), new macrolides such as clarithromycin and azithromycin, and new quinolones including sparfloxacin, ofloxacin, ciprofloxacin, fleroxacin, AM-1155 and so on. Their in vitro antimycobacterial activities, therapeutic efficacy against experimental infections induced in animals especially in mice, and clinical trials using these drugs are summarized by referring to recent studies by worldwide investigators including us. Moreover, this paper dealt with some of recent attempts for chemotherapy of mycobacterial infections employing the drug delivery system using liposomal microvesicles as a carrier of drugs. Although these new drugs and development in new regimens appreciably potentiated the efficacy of controlling mycobacterial infections, in particular M. avium complex infections, it remains very difficult to achieve a complete elimination of the organisms from the sites of infection, even if provided multi-drug regimens using new drugs having excellent antimycobacterial activity and sufficient dosages. Therefore, it seems important to make an effort to elucidate the mechanisms of induction of immuno-unresponsiveness in hosts in progressed state of mycobacterial infection, as well as to develop new drugs possessing more potent antimycobacterial activity.