Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

Abstract

ABSTRACTMacrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment forMycobacterium aviumcomplex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZMCmaxwas measured in patients receiving daily therapy (250 mg of AZM daily,n= 77) or intermittent therapy (500 mg of AZM three times weekly,n= 89) for MAC-LD and daily therapy forMycobacterium abscessuscomplex LD (MABC-LD) (250 mg of AZM daily,n= 55). The AZMCmaxwas lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml;P< 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml;P< 0.001). After adjusting for confounding factors, AZMCmaxwas independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48;P= 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23,P= 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZMCmaxwas common, whereas a higher AZMCmaxwas associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZMCmax. When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.)