Clofazimine-Containing Regimen for the Treatment of Mycobacterium abscessus Lung Disease

ABSTRACT Patients with lung disease caused by Mycobacterium abscessus subsp. abscessus (here M. abscessus) typically have poor treatment outcomes. Although clofazimine (CFZ) has been increasingly used in the treatment of M. abscessus lung disease in clinical practice, there are no reported data on its effectiveness for this disease. This study sought to evaluate the clinical efficacy of a CFZ-containing regimen for the treatment of M. abscessus lung disease. We performed a retrospective review of the medical records of 42 patients with M. abscessus lung disease who were treated with CFZ-containing regimens between November 2013 and January 2015. CFZ was administered in combination with other antibiotics as an initial antibiotic regimen in 15 (36%) patients (initial treatment group), and it was added to an existing antibiotic regimen for refractory M. abscessus lung disease in 27 (64%) patients (salvage treatment group). Overall, there was an 81% treatment response rate based on symptoms and a 31% response rate based on radiographic findings. Conversion to culture-negative sputum samples was achieved in 10 (24%) patients after CFZ-containing antibiotic treatment, and during treatment, there were significant decreases in the positivity of semiquantitative sputum cultures for acid-fast bacilli in both the initial (P = 0.018) and salvage (P = 0.001) treatment groups. Our study suggests that CFZ-containing regimens may improve treatment outcomes in patients with M. abscessus lung disease and that a prospective evaluation of CFZ in M. abscessus lung disease is warranted.

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Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with Mycobacterium avium Complex and Mycobacterium abscessus Complex

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01105-18 ◽

2018 ◽

Vol 62 (10) ◽

Cited By ~ 4

Author(s):

Sun Hye Shin ◽

Byung Woo Jhun ◽

Su-Young Kim ◽

Junsu Choe ◽

Kyeongman Jeon ◽

...

Keyword(s):

Lung Disease ◽

Treatment Outcomes ◽

Mycobacterium Avium ◽

Mixed Infection ◽

Mycobacterium Abscessus ◽

Limited Data ◽

Content Type ◽

Nontuberculous Mycobacterial Lung Disease ◽

Conversion Rates ◽

Ntm Lung Disease

ABSTRACT Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus (25% [3/12]) than in patients infected with MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.

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Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01146-17 ◽

2017 ◽

Vol 61 (10) ◽

Cited By ~ 16

Author(s):

Hayoung Choi ◽

Su-Young Kim ◽

Dae Hun Kim ◽

Hee Jae Huh ◽

Chang-Seok Ki ◽

...

Keyword(s):

Lung Disease ◽

Treatment Outcomes ◽

Point Mutations ◽

Mycobacterium Abscessus ◽

Macrolide Resistance ◽

Clinical Isolates ◽

23S Rrna ◽

Molecular Characteristics ◽

Rrna Gene ◽

Content Type

ABSTRACT Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant Mycobacterium abscessus subsp. abscessus. This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.

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The Clarithromycin Susceptibility Genotype Affects the Treatment Outcome of Patients withMycobacterium abscessusLung Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02360-17 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 7

Author(s):

Qi Guo ◽

Haiqing Chu ◽

Meiping Ye ◽

Zhemin Zhang ◽

Bing Li ◽

...

Keyword(s):

Treatment Outcome ◽

Lung Disease ◽

Treatment Outcomes ◽

Mycobacterium Abscessus ◽

Response To Treatment ◽

Resistant Genotype ◽

Content Type ◽

Therapeutic Outcomes ◽

Microbiological Characteristics ◽

Negative Conversion

ABSTRACTMycobacterium abscessusaccounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria. The association between clarithromycin sensitivity and treatment outcome is clear. However,M. abscessusculture and antibiotic susceptibility testing are time-consuming. Clarithromycin susceptibility genotyping offers an alternate, rapid approach to predicting the efficacy of clarithromycin-based antibiotic therapy.M. abscessuslung disease patients were divided into two groups based upon the clarithromycin susceptibility genotype of the organism isolated. A retrospective analysis was conducted to compare the clinical features, microbiological characteristics, and treatment outcomes of the two groups. Several other potential predictors of the response to treatment were also assessed. Sixty-nine patients were enrolled in the clarithromycin-resistant genotype group, which included 5 infected withrrl2058-2059 mutants and 64 infected witherm(41)T28-typeM. abscessus; 31 were in the clarithromycin-sensitive group, i.e., 6 and 25 patients infected with genotypeserm(41)C28 anderm(41) M type, respectively. The results showed that lung disease patients infected with clarithromycin-sensitive and -resistantM. abscessusgenotypes differed significantly in clarithromycin-based combination treatment outcomes. Patients infected with the clarithromycin-sensitive genotype exhibited higher initial and final sputum-negative conversion and radiological improvement rates and better therapeutic outcomes. Multivariate analysis demonstrated that genotyping was a reliable and, more importantly, rapid means of predicting the efficacy of clarithromycin-based antibiotic treatment forM. abscessuslung disease.

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Long-term clinical course and outcomes of immunoglobulin G4-related lung disease

Respiratory Research ◽

10.1186/s12931-020-01542-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Jieun Kang ◽

Shinhee Park ◽

Eun Jin Chae ◽

Joon Seon Song ◽

Hee Sang Hwang ◽

...

Keyword(s):

Lung Function ◽

Partial Response ◽

Pulmonary Function ◽

Lung Disease ◽

Treatment Outcomes ◽

Response Rate ◽

Clinical Course ◽

Complete Response ◽

Immunoglobulin G4

Abstract Background Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. Methods Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. Results The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. Conclusions Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

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Rifabutin Is Active against Mycobacterium abscessus in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01943-19 ◽

2019 ◽

Vol 64 (2) ◽

Cited By ~ 8

Author(s):

Thomas Dick ◽

Sung Jae Shin ◽

Won-Jung Koh ◽

Véronique Dartois ◽

Martin Gengenbacher

Keyword(s):

Lung Disease ◽

Mycobacterium Abscessus ◽

Content Type

ABSTRACT There is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus. Here, we report that rifabutin is as active as clarithromycin against M. abscessus K21 in NOD.CB17-Prkdcscid/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with M. abscessus disease.

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Clinical Characteristics and Treatment Outcomes of Patients with Macrolide-Resistant Mycobacterium massiliense Lung Disease

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02189-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 9

Author(s):

Hayoung Choi ◽

Su-Young Kim ◽

Hyun Lee ◽

Byung Woo Jhun ◽

Hye Yun Park ◽

...

Keyword(s):

Antibiotic Therapy ◽

Lung Disease ◽

Treatment Outcomes ◽

Mortality Rates ◽

Macrolide Resistance ◽

Clinical Isolates ◽

23S Rrna ◽

Rrna Gene ◽

Content Type ◽

Mycobacterium Massiliense

ABSTRACT Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M. massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M. massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M. massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M. massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M. massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.

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Progression and Treatment Outcomes of Lung Disease Caused by Mycobacterium abscessus and Mycobacterium massiliense

Clinical Infectious Diseases ◽

10.1093/cid/ciw723 ◽

2016 ◽

Vol 64 (3) ◽

pp. 301-308 ◽

Cited By ~ 62

Author(s):

Jimyung Park ◽

Jaeyoung Cho ◽

Chang-Hoon Lee ◽

Sung Koo Han ◽

Jae-Joon Yim

Keyword(s):

Lung Disease ◽

Treatment Outcomes ◽

Lung Diseases ◽

Mycobacterium Abscessus ◽

Progression Rate ◽

Time To Progression ◽

Mycobacterium Massiliense ◽

The Difference ◽

Bilateral Lung ◽

Culture Conversion

Abstract Background Mycobacterium abscessus and Mycobacterium massiliense are grouped as the Mycobacterium abscessus complex. The aim of this study was to elucidate the differences between M. abscessus and M. massiliense lung diseases in terms of progression rate, treatment outcome, and the predictors thereof. Methods Between 1 January 2006 and 30 June 2015, 56 patients and 54 patients were diagnosed with M. abscessus and M. massiliense lung diseases, respectively. The time to progression requiring treatment and treatment outcomes were compared between the 2 groups of patients, and predictors of progression and sustained culture conversion with treatment were analyzed. In addition, mediation analysis was performed to evaluate the effect of susceptibility to clarithromycin on treatment outcomes. Results During follow-up, 21 of 56 patients with M. abscessus lung diseases and 21 of 54 patients with M. massiliense lung diseases progressed, requiring treatment. No difference was detected in the time to progression between the 2 patient groups. Lower body mass index, bilateral lung involvement, and fibrocavitary-type disease were identified as predictors of disease progression. Among the patients who began treatment, infection with M. massiliense rather than M. abscessus and the use of azithromycin rather than clarithromycin were associated with sustained culture conversion. The difference in treatment outcomes was partly mediated by the organism’s susceptibility to clarithromycin. Conclusions Progression rates were similar but treatment outcomes differed significantly between patients with lung disease caused by M. abscessus and M. massiliense. This difference in treatment outcomes was partly explained by the susceptibility of these organisms to clarithromycin.

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Mycobacterium abscessusCells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02488-18 ◽

2019 ◽

Vol 63 (7) ◽

Cited By ~ 7

Author(s):

Augusto Cesar Hunt-Serracin ◽

Brian J. Parks ◽

Joseph Boll ◽

Cara C. Boutte

Keyword(s):

Cystic Fibrosis ◽

Multidrug Resistant ◽

Mycobacterium Abscessus ◽

Cell Physiology ◽

Antibiotic Tolerance ◽

Planktonic Cells ◽

Content Type ◽

Cystic Fibrosis Sputum ◽

Poor Treatment ◽

Nutrient Conditions

ABSTRACTMycobacterium abscessusis a biofilm-forming, multidrug-resistant nontuberculous mycobacterial (NTM) pathogen increasingly found in cystic fibrosis patients. Antibiotic treatment for these infections is often unsuccessful, partly due toM. abscessus’s high intrinsic antibiotic resistance. It is not clear whether antibiotic tolerance caused by biofilm formation also contributes to poor treatment outcomes. We studied the surface glycolipids and antibiotic tolerance ofM. abscessusbiofilms grown in artificial cystic fibrosis sputum (ACFS) medium to determine how they are affected by nutrient conditions that mimic infection. We found thatM. abscessusdisplays more of the virulence lipid trehalose dimycolate when grown in ACFS than when grown in standard lab medium. In ACFS medium, biofilm-associated cells were more antibiotic tolerant than planktonic cells in the same well. This contrasts with standard lab media, where both biofilm and planktonic cells are highly antibiotic tolerant. These results indicate thatM. abscessuscell physiology in biofilms depends on environmental factors and that nutrient conditions found within cystic fibrosis infections could contribute to both increased virulence and antibiotic tolerance.

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Mycobacterial Characteristics and Treatment Outcomes in Mycobacterium abscessus Lung Disease

Clinical Infectious Diseases ◽

10.1093/cid/ciw724 ◽

2016 ◽

Vol 64 (3) ◽

pp. 309-316 ◽

Cited By ~ 91

Author(s):

Won-Jung Koh ◽

Byeong-Ho Jeong ◽

Su-Young Kim ◽

Kyeongman Jeon ◽

Kyoung Un Park ◽

...

Keyword(s):

Lung Disease ◽

Treatment Outcomes ◽

Antibiotic Treatment ◽

Mycobacterium Abscessus ◽

Disease Treatment ◽

Microbial Characteristics ◽

Subspecies Level ◽

Genotypic Analysis ◽

Sputum Conversion ◽

Negative Conversion

Abstract Background Treatment outcomes of patients with Mycobacterium abscessus subspecies abscessus lung disease are poor, and the microbial characteristics associated with treatment outcomes have not been studied systematically. The purpose of this study was to identify associations between microbial characteristics and treatment outcomes in patients with M. abscessus lung disease. Methods Sixty-seven consecutive patients with M. abscessus lung disease undergoing antibiotic treatment for ≥12 months between January 2002 and December 2012 were included. Morphotypic and genetic analyses were performed on isolates from 44 patients. Results Final sputum conversion to culture negative occurred in 34 (51%) patients. Compared to isolates from 24 patients with persistently positive cultures, pretreatment isolates from 20 patients with final negative conversion were more likely to exhibit smooth colonies (9/20, 45% vs 2/24, 8%; P = .020), susceptibility to clarithromycin (7/20, 35% vs 1/24, 4%; P = .015), and be of the C28 sequevar with regard to the erm(41) gene (6/20, 30% vs 1/24, 4%; P = .035). Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Genotypic analysis revealed that most episodes (22/24, 92%) of persistently positive cultures during antibiotic treatment and all cases of microbiologic recurrence after treatment completion were caused by different M. abscessus genotypes within a patient. Conclusions Precise identification to the subspecies level and analysis of mycobacterial characteristics could help predict treatment outcomes in patients with M. abscessus lung disease. Treatment failures and recurrences are frequently associated with multiple genotypes, suggesting reinfection. Clinical Trials Registration NCT00970801.

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