[Nontuberculous mycobacteriosis; the present status and in the future. 3--(1). The view of development of new drugs against nontuberculous mycobacterial infections].

Abstract It is obvious that the number of patients with pulmonary nontuberculous mycobacterial infections is increasing gradually in Japan. Of these infections, M. avium complex (MAC) is the most common cause, and is known to be resistant to many antimicrobial drugs. At present, no standard regimen which is able to control MAC infections completely is established. For these reasons, the development of new drugs with strong antimycobacterial activity which are not cross-resistant to conventional antimycobacterial drugs is urgently desired. Thus, we studied in vitro activities of various drugs which are expected to be a new promising drug against nontuberculous mycobacterial infections, and reviewed clinical impact of these drugs. 1) New quinolones New quinolones including ofloxacin, ciprofloxacin, levofloxacin and sparfloxacin (SPFX), are considered to be active against M. tuberculosis, M. kansasii, M. fortuitum, but are inactive against MAC, M. chelonae, M. abscessus, M. scrofulaceum. Both AM-1155 and Du-6859a, newer quinolones, seemed to be comparable to or more active than SPFX which is considered to be most active now. 2) New macrolides Clarithromycin (CAM) has in vitro activities against various nontuberculous mycobacteria including MAC, and also has proven to have clinical potential not only for disseminated MAC infections in AIDS but also for pulmonary MAC infections. Therefore, CAM seems to be a candidate for one of the key drugs in the treatment of MAC infections. 3)Rifamycins Rifabutin (RBT) and rifapentine exhibited more potent in vitro and in vivo antimycobacterial activities than rifampicin. RBT has already demonstrated clinical effect against intractable tuberculosis and MAC infections. Thus, RBT is recommended for the prophylaxis of M. tuberculosis and MAC infections in AIDS patients in US. KRM-1648 displayed much more potent in vitro and in vivo activities than rifampicin against both M. tuberculosis and MAC. It is needed an effort to confirm its therapeutic efficacies. Now clinical phase study is going on in US. 4) Phenazines Clofazimine (CFZ), an effective antileprosy drug, is known to be active in vitro against various mycobacteria including MAC, and often used as a component of combination chemotherapy for disseminated MAC infections in AIDS patients in US. Recently, CFZ new analogs have been developed, and it is necessary to evaluate its activities against nontuberculous mycobacteria.