2016 Volume 42 Issue 12 Pages 781-794
The incidence of pulmonary Mycobacterium avium complex (MAC) disease is increasing worldwide. Currently, clarithromycin is the key drug for treatment of pulmonary MAC disease, and multidrug therapy with rifampicin and ethambutol is recommended. However, the efficacy of this therapy is reported to be approximately 60-80％. Therefore, this disease is often difficult to treat, and there are some problems concerning this form of chemotherapy. Firstly, rifampicin decreases the serum clarithromycin concentration owing to CYP3A4-related interactions. Although this therapy needs to be administered for more than one year, to our knowledge, no study has investigated the long-term relationship between serum clarithromycin and rifampicin concentrations and CYP3A4 activity, together with treatment efficacy. Secondly, an alternative treatment to the recommended therapy of clarithromycin, rifampicin, and ethambutol has not been established. Therefore, fluoroquinolones are often used when the clinical efficacy of the recommended regimen is insufficient. However, very few previous studies have investigated the clinical efficacy of the combination of clarithromycin and fluoroquinolones, especially levofloxacin.
Our recent study demonstrated that serum clarithromycin concentrations in patients with pulmonary MAC disease were continuously low because of rifampicin-mediated CYP3A4 induction, which may be responsible for the unsatisfactory clinical outcomes observed. We also investigated the clinical outcomes achieved with the currently recommended dose of clarithromycin and levofloxacin, and suggested the possibility that combined administration of clarithromycin and levofloxacin did not improve clinical outcomes for the treatment of pulmonary MAC disease. In this mini-review, we summarize the findings of our clinical studies concerning chemotherapy for pulmonary MAC disease.
