Peak plasma concentration of azithromycin and treatment responses in mycobacterium avium complex lung disease

Byeong Ho Jeong, Kyeongman Jeon, Hye Yun Park, Seong Mi Moon, Su Young Kim, Soo Youn Lee, Sung Jae Shin, Charles L. Daley, Won Jung Koh

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11 Citations (Scopus)

Abstract

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 (Cmax) of AZM. The AZM Cmax 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 Cmax was 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, AZM Cmax 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 Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax. 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.

Original languageEnglish
Pages (from-to)6076-6083
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number10
DOIs
Publication statusPublished - 2016 Oct

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Jeong, B. H., Jeon, K., Park, H. Y., Moon, S. M., Kim, S. Y., Lee, S. Y., Shin, S. J., Daley, C. L., & Koh, W. J. (2016). Peak plasma concentration of azithromycin and treatment responses in mycobacterium avium complex lung disease. Antimicrobial agents and chemotherapy, 60(10), 6076-6083. https://doi.org/10.1128/AAC.00770-16