[Perspective of pulmonary MAC infection treatment].
Chemotherapy of pulmonary MAC (Mycobacterium avium complex) infection has been almost universally agreed with the multidrugs regimen that contains Clarithromycin (CAM), Rifampin (RFP), Ethambtol (EB), and aminoglycoside in case of advanced stage. One of the reason for the multidrugs regimen which is similar to tuberculous chemotherapy is to inhibit the emersion of resistant MAC strain. The other reasons, enhancement of anti microbial activity and response to polyclonal infection are unique to the MAC chemotherapy. In the current MAC chemotherapy, both CAM and aminoglycoside are main axes because only they can suppress the growth of MAC alone respectively. Efficacy of CAM was revealed through the randomized controlled trials of disseminated MAC infection with HIV and that consequences applied to pulmonary MAC infection treatment. CAM is not effective unless exceed 2 microg/ml blood concentration. RFP decreases CAM blood concentration remarkably, but the regimens contained RFP and CAM are superior clinically to the regimens without RFP. There seemed to be unknown pharmacological mechanisms with RFP. Although the advantage of aminoglycosides is easily achieved high blood concentration, if aminoglycoside dosage is exceed 15 mg/kg, the possibility of auditory disturbance increase. About the duration of MAC chemotherapy, many guidelines recommended that one year continuation after the negative conversion of sputum culture. It is not the evidence but an expert opinion. We often experience recurrences several months later after the all drugs are ceased. The interval days to positive conversion of sputum culture from the day of completion of chemotherapy are randomly distributed with weibull's equation. It suggests that exogenous re-infection may cause the recurrence of pulmonary MAC infection as pointed out by Wallace Jr. Considering these issues, we have the conception of pulmonary MAC infection chemotherapy as follows. 1. Full dose induction chemotherapy (two years). 2. Maintenance chemotherapy (one year). 3. Preventive chemotherapy (one year). These conceptions have to be the problem validated. However, these current chemotherapies are not effective adequately, we need the combination treatment with surgical resection when indicated as a localized focus for example. Generally chemotherapy could not cured the destructed bronchial lesion due to MAC infection as like as local bronchiectasis or cavities. Consequently, the chemotherapy just after the surgical resection of destructed focus is most appropriate period.
Kurashima
Atsuyuki
A
Division of Clinical Research, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo 204-8585, Japan. krsm@tokyo.hosp.go.jp
D000617:Aminoglycosides / Q000008:administration & dosage; D000995:Antitubercular Agents / Q000008:administration & dosage*; D017291:Clarithromycin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage; D019317:Evidence-Based Medicine; D006801:Humans; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000601:surgery; D017410:Practice Guidelines as Topic; D012293:Rifampin / Q000008:administration & dosage; D055502:Secondary Prevention; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000601:surgery
D000617:Aminoglycosides; D000995:Antitubercular Agents; D004977:Ethambutol; D017291:Clarithromycin; D012293:Rifampin