[Chemotherapy of pulmonary Mycobacterium kansasii infection]

A very favorable outcome after chemotherapy of 122 cases of M. kansasii lung disease was reported by Dr. Mizutani, who emphasized RFP as the "Key drug", and concluded that three-drug combination (not two-drug), including RFP (RFP.INH.EB or SM) for 1 year, could be a standard regimen for M. kansasii lung disease at the time of the moment. In addition, the following itemes were discussed. (1) In cases resistant to RFP, one could possibly replace RFP by TH, one of new quinolones (NQ), or the new macrolide (NM) (clarithromycin, CAM). (2) In low grade resistant cases to INH (0.1 microgram /ml) or EB (2.5 micrograms/ml), the replacement of the drugs may not be necessary, however, in higher-grade resistance to INH or EB, many cases were looked for the change of drugs according the results of the questionnaire done by the author. The present status of basic preclinical evaluations of new drugs were presented by Dr. Tomioka, who summarized in vitro and in vivo antimycobacterial activities of NMs and NQs. The most potent activity among NMs was demonstrated in CAM, which is probably the candidate for M. kansasii and possibly for M. avium complex (MAC) disease, followed by roxithromycin (RXM) and azithromycin (AZM) in sequence. NQs including the ones under development were generally potent against Mycobacterium tuberculosis, M. kansasii and M. fortuitum. NQs were not potent enough for MAC. In addition, the author discussed more suitable in vitro techniques which should reflect in vivo evaluations, and proposed the observation of in vitro bactericidal activity using both Cmax (maximal in vivo concentration) and C (0-8h) (the average concentration during 8 hours after administration) of drugs, and also the assessment of bactericidal activities of drugs in macrophages as better choices. As additional comments, the results of in vitro activities of NQs and NMs against MAC were supplemented by two authors, Dr. Tsuyuguchi and Dr. Kawahara. The assessment using 7 H 9 liquid medium by the former author demonstrated the potent activities of both CS-940* and sparfloxacin (SPFX), followed by AM-1155*, ciprofloxacin (CPFX), levofloxacin (LVFX), OPC-17116*, NM-394* in sequence. The author gave attention also to a high Cmax in CS-940*. In vitro activities with 7 H 11 agar medium reported by Dr. Kawahara demonstrated generally higher activities against M. avium than M. intracellulare, and reported potent activities of CPFX, SPFX, LVFX, grepafloxacin (GPFX), AM-1155*, and DU-6859 a* among 14 NQs tested. The author reported a rather potent activity of CAM against MAC followed by RXM and AZM in sequence. There was an impression that the MICs in both liquid and agar medium were comparable. (* : under development). The present status in the treatment of MAC lung disease was precisely reported by Dr. Harada, who summarized the results of survey both in 13 National Chest Hospitals (by questionnaire) and in the author's Hospital. The former survey demonstrated that 73% of the cases with the initial chemotherapy became consecutively negative for 6 months in the span of 9 months observation, which clearly showed the early response of MAC disease was rather favorable, in spite of very few cases with 4 drug-or more combinations. However, longer the follow up, the percentage of negative cases went down, which suggested bacteriological relapse occurred in relatively high percentage of the early converted cases. The evaluation of 117 cases of pulmonary MAC disease in the author's Hospital disclosed 2 drug-combination, RFP and INH, was clearly less potent than 3-drug combination, RFP.IHN.SM or EB, and 1 year after the begining of initial chemotherapy, around 60% of cases were negative, while only a little more than 40% of cases were negative in retreatments. The author suggested that around 50% of MAC lung disease may progress with episodes of "relapse". Death occurred 20% in the cases