Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with Mycobacterium avium complex pulmonary disease

Abstract

Objectives Clarithromycin (CAM) is widely accepted for the treatment of Mycobacterium avium complex (MAC) pulmonary diseases. This study measured (a) the concentrations of CAM and its active metabolite (14OH-CAM) in bronchial epithelial lining fluid (ELF) obtained by bronchoscopic microsampling (BMS), and (b) the minimal inhibitory concentrations (MIC) of CAM for each MAC isolate. Methods We studied eight patients with MAC pulmonary disease treated with oral CAM, 400 ( n = 4) or 800 ( n = 4) mg/day. BMS was performed 3 h after the last CAM dose, and the concentrations of CAM and 14OH-CAM were measured in ELF collected from the diseased and normal contralateral pulmonary segments, and in serum. Results The mean ± SEM ELF concentrations of CAM (23.85 ± 7.64 μg/ml) and CAM + 14OH-CAM (28.71 ± 8.37 μg/ml) in the 800 mg/day treatment group were significantly higher than in the 400 mg/day group (7.48 ± 2.58 μg/ml and 9.63 ± 2.99 μg/ml, respectively; both p < 0.05), while the serum concentrations were similar in both groups. In both treatment groups, the mean ELF concentrations sampled from diseased and normal segments were higher than the MIC against MAC isolates. The mean ELF concentration of CAM in the 400 mg/day treatment group was <8 μg/ml (the breakpoint concentration of CAM against M. avium recommended by the Clinical Laboratories Standards Institute), while the mean concentration in the 800 mg/day treatment group was >8 μg/ml. Conclusion These observations suggest that CAM, 800 mg/day, is an appropriate dose to treat MAC pulmonary disease, and prevent its spread from diseased to non-diseased lung segments.