Treatment of Mycobacterium avium Complex Pulmonary Disease

권용수,고원중,Charles L. Daley 대한결핵및호흡기학회 2019 Tuberculosis and Respiratory Diseases Vol.82 No.1

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Treatment of Mycobacterium avium Complex Pulmonary Disease

Kwon, Yong-Soo,Koh, Won-Jung,Daley, Charles L. The Korean Academy of Tuberculosis and Respiratory 2019 Tuberculosis and Respiratory Diseases Vol.82 No.1

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

REVIEW : Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians` Perspectives

( Yon Ju Ryu ),( Won Jung Koh ),( Charles L. Daley ) 대한결핵 및 호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.2

Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article.

Treatment of Mycobacterium avium Complex Pulmonary Disease

( Yong-soo Kwon ),( Won-jung Koh ),( Charles L. Daley ) 대한결핵 및 호흡기학회 2019 Tuberculosis and Respiratory Diseases Vol.82 No.1

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

Unresolved issues in treatment outcome definitions for nontuberculous mycobacterial pulmonary disease

Moon, Seong Mi,Jhun, Byung Woo,Daley, Charles L.,Koh, Won-Jung ERS Journals Ltd 2019 The European respiratory journal Vol.53 No.5

<P>The incidence and prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide [1, 2]. NTM-PD treatment is challenging due to long-term, multiple antibiotic therapy and poor treatment outcomes [3, 4]. Standardised treatment outcome definitions for NTM-PD were recently reported in the Nontuberculous Mycobacteria Network European Trials Group (NTM-NET) consensus statement [5], and are an important development for patient management and clinical research [5].</P>

Prognostic factors associated with long-term mortality in 1,445 patients with non-tuberculous mycobacterial pulmonary disease

전병우,문성미,전경만,권오정,유희진,조금희,( Charles L. Daley ),고원중 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

We investigated the prognostic factors associated with long-term mortality in nontuberculous mycobacterial pulmonary disease (NTM-PD) patients with data on radiological type and etiologic organisms. In total, 1,445 patients diagnosed with treatment- naïve NTM-PD between July 1997 and December 2013 were included. The distribution of NTM etiology was as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus subspecies abscessus (M. abcessus, n=129), or M. abscessus subspecies massiliense (M. massiliense, n=174). Factors associated with mortality were analyzed using a multivariable Cox model adjusted for demographic, radiographic, and etiologic data. The overall 5-, 10-, and 15-year cumulative mortality rates of NTM-PD were 12.4%, 24.0%, and 36.4%, respectively. The multivariable analysis showed that old age, male, low body mass index, chronic pulmonary aspergillosis, pulmonary or extra-pulmonary malignancy, and chronic heart or liver disease were significantly and negatively associated with mortality. Causative NTM organism (reference M. avium) was significantly associated with mortality: M. intracellulare (adjusted hazard ratio [aHR]=1.42; 95% confidence interval [CI]=1.04-1.95), M. abscessus (aHR=2.12; 95% CI=1.32-3.41), and M. massiliense (aHR=0.97, 95% CI=0.59-1.6). Mortality was also significantly associated with the radiological type of NTM-PD, especially in cavitary diseases (log-rank test; p<0.0001). In conclusion, NTM organisms and cavitary disease as well as demographic characteristics were associated with long-term mortality in NTM-PD.

Mycobacterium abscessus pulmonary disease : individual patient data meta-analysis

( Nakwon Kwak ),( Margareth Pretti Dalcolmo ),( Charles L. Daley ),( Geoffrey Eather ),( Regina Gayoso ),( Naoki Hasegawa ),( Byung Woo Jhun ),( Won-jung Koh ),( Ho Namkoong ),( Jimyung Park ),( Rache 대한결핵 및 호흡기학회 2018 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.126 No.-

Background: Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), which is caused by subspecies M. abscessus subspecies abscessus (M. abscessus), M. abscessus subspecies massiliense (M. massiliense), or M. abscessus subspecies bolletii, is challenging. Methods: We conducted an individual patient data meta-analysis based on published studies reporting treatment outcomes for MAB-PD to clarify the treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Results: A total of 303 patients with MAB-PD from eight studies were included. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus and 56.7% for M. massiliense pulmonary disease. For MAB-PD, the use of imipenem was associated with treatment success (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.36-5.10). For patients with M. abscessus, the use of azithromycin (aOR, 3.29; 95% CI, 1.26-8.62), amikacin (aOR, 1.44; 95% CI, 1.05-1.99), or imipenem (aOR, 7.96; 95% CI, 1.52-41.6) increased the likelihood of treatment success. For patients with M. massiliense, the choice among these drugs did not affect the treatment outcomes. Conclusion: Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin, or imipenem improves treatment outcomes for patients with M. abscessus pulmonary disease.

Treatment of macrolide-containing regimens for Mycobacterium kansasii pulmonary disease

최준수,문성미,전병우,전경만,권오정,허희재,이남용,( Charles L. Daley ),고원중 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.1

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives

Ryu, Yon Ju,Koh, Won-Jung,Daley, Charles L. The Korean Academy of Tuberculosis and Respiratory 2016 Tuberculosis and Respiratory Diseases Vol.79 No.2

Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article.

F-22 Development of Macrolide Resistance and Reinfection in Patients with Refractory Mycobacterium avium Complex Lung Disease

전병우,문성미,김수영,박혜윤,전경만,권오정,허희재,기창석,이남용,신성재,( Charles L. Daley ),고원중 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Treatment outcomes of Mycobacterium avium complex lung disease (MAC-LD) have occasionally been unsatisfactory despite long-term antibiotic therapy. The aim of this study was to evaluate the incidence of development of macrolide resistance and the proportion of reinfection rate in patients with refractory MAC-LD. Among 566 patients with treatment-naive MAC-LD who started antibiotic treatment betwwen January 2002 and December 2013, we identified 72 refractory MAC-LD patients with persistent sputum culture despite more than 12 months of treatment. Macrolide resistance was developed in only 15 (21%) patients. Median time to occurrence of macrolide resistance from starting treatment was 58.8 months (interquartile range, 42.3-85.9 months). Of the 49 patients who had both pretreatment and more than one on-treatment sputum isolates, bacterial genotyping revealed that reinfection by new MAC strains developed in 36 (73%) patients; the new strains were found in 24 (49%) patients and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had a persistent infection by same MAC strains. Our data suggest that the refractory MAC-LD is commonly caused by frequent reinfection with new strains rather than persistence of original strains, and these may explain the lower incidence of macrolide resistance in refractory MAC-LD despite long-term antibiotic therapy.