title: Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.
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. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.).
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Byeong-Ho
authors.initials: BH
authors.lastname: Jeong
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Kyeongman
authors.initials: K
authors.lastname: Jeon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Park
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Seong Mi
authors.initials: SM
authors.lastname: Moon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea wjkoh@skku.edu.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004977:Ethambutol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000254:growth & development; D015270:Mycobacterium avium-intracellulare Infection / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D004977:Ethambutol; D012293:Rifampin