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

doi:10.1128/AAC.00770-16

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

Department of Microbiology

Research output: Contribution to journal › Article › peer-review

30 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 (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 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 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.

Original language	English
Pages (from-to)	6076-6083
Number of pages	8
Journal	Antimicrobial agents and chemotherapy
Volume	60
Issue number	10
DOIs	https://doi.org/10.1128/AAC.00770-16
Publication status	Published - 2016 Oct

Bibliographical note

Funding Information:
We thank Byung Woo Jhun (The Armed Forces Capital Hospital, Seongnam, South Korea) for valuable comments on the manuscript. Charles L. Daley has received grants from Insmed, Inc. that are not associated with the submitted work. We have no other conflicts of interest to declare. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2015R1A2A1A01003959), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant HI15C2778). This work, including the efforts of Won-Jung Koh, was funded by National Research Foundation of Korea (NRF) (NRF-2015R1A2A1A01003959). This work, including the efforts of Won-Jung Koh, was funded by Korea Health Industry Development Institute (KHIDI) (HI15C2778). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
Copyright © 2016, American Society for Microbiology. All Rights Reserved.

All Science Journal Classification (ASJC) codes

Pharmacology
Pharmacology (medical)
Infectious Diseases

UN SDGs

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10.1128/AAC.00770-16

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@article{f37ac82030de4023a621158e560839bb,

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.",

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

note = "Funding Information: We thank Byung Woo Jhun (The Armed Forces Capital Hospital, Seongnam, South Korea) for valuable comments on the manuscript. Charles L. Daley has received grants from Insmed, Inc. that are not associated with the submitted work. We have no other conflicts of interest to declare. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2015R1A2A1A01003959), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant HI15C2778). This work, including the efforts of Won-Jung Koh, was funded by National Research Foundation of Korea (NRF) (NRF-2015R1A2A1A01003959). This work, including the efforts of Won-Jung Koh, was funded by Korea Health Industry Development Institute (KHIDI) (HI15C2778). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: Copyright {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",

year = "2016",

month = oct,

doi = "10.1128/AAC.00770-16",

language = "English",

volume = "60",

pages = "6076--6083",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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T1 - Peak plasma concentration of azithromycin and treatment responses in mycobacterium avium complex lung disease

AU - Jeong, Byeong Ho

AU - Jeon, Kyeongman

AU - Park, Hye Yun

AU - Moon, Seong Mi

AU - Kim, Su Young

AU - Lee, Soo Youn

AU - Shin, Sung Jae

AU - Daley, Charles L.

AU - Koh, Won Jung

N1 - Funding Information: We thank Byung Woo Jhun (The Armed Forces Capital Hospital, Seongnam, South Korea) for valuable comments on the manuscript. Charles L. Daley has received grants from Insmed, Inc. that are not associated with the submitted work. We have no other conflicts of interest to declare. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2015R1A2A1A01003959), and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant HI15C2778). This work, including the efforts of Won-Jung Koh, was funded by National Research Foundation of Korea (NRF) (NRF-2015R1A2A1A01003959). This work, including the efforts of Won-Jung Koh, was funded by Korea Health Industry Development Institute (KHIDI) (HI15C2778). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: Copyright © 2016, American Society for Microbiology. All Rights Reserved.

PY - 2016/10

Y1 - 2016/10

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

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UN SDGs

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