Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease

Rationale: Little is known regarding the application of therapeutic drug monitoring for treatment of Mycobacterium avium complex (MAC) lung disease. Objectives: To evaluate drug interactions of multidrug regimens and clinical usefulness of therapeutic drug monitoring in the management of MAC lung disease. Methods: A total of 130 patients with MAC lung disease and 60 patients with Mycobacterium abscessus complex lung disease were enrolled in this study. All of the MAC patients were treated with multidrug regimens that included clarithromycin (CLR), rifampin (RIF) or rifabutin (RFB), and ethambutol (EMB), and the plasma drug concentrations of CLR, RIF, and EMB were measured. Measurements and Main Results: Peak plasma CLR concentrations were lower in patients with MAC lung disease who received daily (median, 0.3 μg/ml) or intermittent (median, 0.2 μg/ml) therapy with CLR in conjunction with RIF in both groups, compared with those diagnosed with M. abscessus complex lung disease who received CLR without RIF (median, 3.8 μg/ml; P < 0.05). The proportion of patients with MAC lung disease who received daily therapy and whose plasma CLR levels were below the target range of 2 μg/ml was 97% (96 of 99), and this rate was 100% (21 of 21) among patients with MAC lung disease who received intermittent therapy. The peak plasma drug concentrations and the peak plasma drug concentration/minimal inhibitory concentration ratios of CLR, RIF, and EMB did not differ between patients with unfavorable treatment outcomes and those with favorable outcomes. Conclusions: Low plasma CLR concentrations were common in patients treated for MAC lung disease. However, there was no association between low plasma CLR concentrations and treatment outcomes. Therefore, therapeutic drug monitoring may not be beneficial in managing the therapy of patients with MAC lung disease.