In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-c...

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Main Authors: Dae Hun Kim, Bo-Guen Kim, Su-Young Kim, Hee Jae Huh, Nam Yong Lee, Won-Jung Koh, Hojoong Kim, O Jung Kwon, Byung Woo Jhun
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/10/19/4581
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author Dae Hun Kim
Bo-Guen Kim
Su-Young Kim
Hee Jae Huh
Nam Yong Lee
Won-Jung Koh
Hojoong Kim
O Jung Kwon
Byung Woo Jhun
author_facet Dae Hun Kim
Bo-Guen Kim
Su-Young Kim
Hee Jae Huh
Nam Yong Lee
Won-Jung Koh
Hojoong Kim
O Jung Kwon
Byung Woo Jhun
author_sort Dae Hun Kim
collection DOAJ
description Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 <i>Mycobacterium avium</i>, 53/57 <i>M. intracellulare</i>, 49/52 <i>M. kansasii</i>, 22/64 <i>M. abscessus</i>, and 57/67 <i>M. massiliense</i>). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 <i>M. abscessus</i>, 9/9 <i>M. massiliense</i>, 0/1 <i>M. avium</i>, and 1/1 <i>M. intracellulare</i>). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, <i>p</i> = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.
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spelling doaj.art-bf921f14f23a4355af2229ef6b65b34c2023-11-22T16:21:35ZengMDPI AGJournal of Clinical Medicine2077-03832021-10-011019458110.3390/jcm10194581In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary DiseaseDae Hun Kim0Bo-Guen Kim1Su-Young Kim2Hee Jae Huh3Nam Yong Lee4Won-Jung Koh5Hojoong Kim6O Jung Kwon7Byung Woo Jhun8Samsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaSamsung Medical Center, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaLimited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 <i>Mycobacterium avium</i>, 53/57 <i>M. intracellulare</i>, 49/52 <i>M. kansasii</i>, 22/64 <i>M. abscessus</i>, and 57/67 <i>M. massiliense</i>). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 <i>M. abscessus</i>, 9/9 <i>M. massiliense</i>, 0/1 <i>M. avium</i>, and 1/1 <i>M. intracellulare</i>). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, <i>p</i> = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.https://www.mdpi.com/2077-0383/10/19/4581nontuberculous mycobacteriaclofaziminein vitrominimum inhibitory concentrationminimum bactericidal concentration
spellingShingle Dae Hun Kim
Bo-Guen Kim
Su-Young Kim
Hee Jae Huh
Nam Yong Lee
Won-Jung Koh
Hojoong Kim
O Jung Kwon
Byung Woo Jhun
In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
Journal of Clinical Medicine
nontuberculous mycobacteria
clofazimine
in vitro
minimum inhibitory concentration
minimum bactericidal concentration
title In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
title_full In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
title_fullStr In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
title_full_unstemmed In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
title_short In Vitro Activity and Clinical Outcomes of Clofazimine for Nontuberculous Mycobacteria Pulmonary Disease
title_sort in vitro activity and clinical outcomes of clofazimine for nontuberculous mycobacteria pulmonary disease
topic nontuberculous mycobacteria
clofazimine
in vitro
minimum inhibitory concentration
minimum bactericidal concentration
url https://www.mdpi.com/2077-0383/10/19/4581
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