Peak Plasma Concentration of Azithromycin and Treatment Responses in <i>Mycobacterium avium</i> Complex Lung Disease

초록

Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex 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 (C-max) of AZM. The AZM C-max was 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 for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM C-max was lower with the daily regimen for MAC-LD (median, 0.24 mu g/ml) than with the intermittent regimen for MAC-LD (median, 0.65 mu g/ml; P< 0.001) or daily therapy for MABC-LD (median, 0.53 mu g/ml; P< 0.001). After adjusting for confounding factors, AZM C(max)was 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 AZM C-max was common, whereas a higher AZM C-max was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM C-max. 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.

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