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

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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Faculty Opinions recommendation of Progression and Treatment Outcomes of Lung Disease Caused by Mycobacterium abscessus and Mycobacterium massiliense.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727254675.793565558 ◽

2019 ◽

Author(s):

Shawn Skerrett

Keyword(s):

Lung Disease ◽

Treatment Outcomes ◽

Mycobacterium Abscessus ◽

Mycobacterium Massiliense

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Impact of susceptibility to injectable antibiotics on the treatment outcomes of Mycobacterium abscessus pulmonary disease

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab215 ◽

2021 ◽

Author(s):

Youngmok Park ◽

Yea Eun Park ◽

Byung Woo Jhun ◽

Jimyung Park ◽

Nakwon Kwak ◽

...

Keyword(s):

Treatment Outcomes ◽

Pulmonary Disease ◽

Drug Susceptibility ◽

Mycobacterium Abscessus ◽

Beta Lactams ◽

In Vitro Susceptibility ◽

Referral Hospitals ◽

Microbiological Cure ◽

Culture Conversion

Abstract Objectives Current guidelines recommend a susceptibility-based regimen for Mycobacterium abscessus subspecies abscessus pulmonary disease (MAB-PD), but the evidence is weak. We aimed to investigate the association between treatment outcomes and in vitro drug susceptibility to injectable antibiotics in MAB-PD patients. Methods We enrolled MAB-PD patients treated with intravenous amikacin and beta-lactams for ≥4 weeks at four referral hospitals in Seoul, South Korea. Culture conversion and microbiological cure at one year were evaluated based on susceptibility to injectable antibiotics among patients treated with those antibiotics for ≥ 2 weeks. Results A total of 82 patients were analysed. The mean age was 58.7 years, and 65.9% were women. Sputum culture conversion and microbiological cure were achieved in 52.4% and 41.5% of patients, respectively. Amikacin was the most common agent to which the M. abscessus subspecies abscessus isolates were susceptible (81.7%); 9.8% and 24.0% of the isolates were resistant to cefoxitin and imipenem, respectively. The clarithromycin-inducible resistance (IR) group (n = 65) had a lower microbiological cure rate than the clarithromycin-susceptible group (35.4% vs. 64.7%). The treatment outcomes appeared to be similar regardless of in vitro susceptibility results with regard to intravenous amikacin, cefoxitin, imipenem, and moxifloxacin. In the subgroup analysis of the clarithromycin-IR group, the treatment outcomes did not differ according to antibiotic susceptibility. Conclusions We did not find evidence supporting the use of susceptibility-based treatment with intravenous amikacin and beta-lactams in patients with MAB-PD. Further research would be required.

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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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Sequential Bilateral Lung Resection in a Patient with Mycobacterium Abscessus Lung Disease Refractory to Medical Treatment

Yonsei Medical Journal ◽

10.3349/ymj.2010.51.1.141 ◽

2010 ◽

Vol 51 (1) ◽

pp. 141 ◽

Cited By ~ 2

Author(s):

Seung Heon Lee ◽

Joo-Won Min ◽

Sang-Won Um ◽

Seon-Sook Han ◽

Sung Koo Han ◽

...

Keyword(s):

Medical Treatment ◽

Lung Disease ◽

Lung Resection ◽

Mycobacterium Abscessus ◽

Bilateral Lung

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02052-16 ◽

2017 ◽

Vol 61 (6) ◽

Cited By ~ 47

Author(s):

Bumhee Yang ◽

Byung Woo Jhun ◽

Seong Mi Moon ◽

Hyun Lee ◽

Hye Yun Park ◽

...

Keyword(s):

Treatment Group ◽

Lung Disease ◽

Treatment Outcomes ◽

Response Rate ◽

Mycobacterium Abscessus ◽

Antibiotic Regimen ◽

Radiographic Findings ◽

Content Type ◽

Poor Treatment ◽

Reported Data

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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Clinical and Microbiological Differences between Mycobacterium abscessus and Mycobacterium massiliense Lung Diseases

Journal of Clinical Microbiology ◽

10.1128/jcm.03072-12 ◽

2013 ◽

Vol 51 (2) ◽

pp. 736-736 ◽

Cited By ~ 1

Author(s):

T. Harada ◽

Y. Akiyama ◽

A. Kurashima ◽

H. Nagai ◽

K. Tsuyuguchi ◽

...

Keyword(s):

Lung Diseases ◽

Mycobacterium Abscessus ◽

Mycobacterium Massiliense

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An Intensified Regimen Containing Linezolid Could Improve Treatment Response in Mycobacterium abscessus Lung Disease

BioMed Research International ◽

10.1155/2019/8631563 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

Hua Li ◽

Li Tong ◽

Jun Wang ◽

Qingtao Liang ◽

Yun Zhang ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Lung Disease ◽

Treatment Response ◽

Conversion Rate ◽

Mycobacterium Abscessus ◽

Sputum Culture Conversion ◽

Conventional Regimen ◽

Sputum Conversion ◽

Culture Conversion

Background. Treatment response for the Mycobacterium abscessus (M. abscessus) lung disease remains far from satisfying. An effective regimen is needed to solve the problem. Methods. We retrospectively reviewed the medical records of all patients with M. abscessus lung disease who received antibiotics regimen at Beijing Chest Hospital Affiliated to Capital Medical University between July 1, 2010, and February 1, 2018. Patients were administered a conventional antibiotics regimen (including macrolide and moxifloxacin, along with an initial 12-week course of low-dose cefoxitin and amikacin) or intensified regimen (including a higher dosage of cefoxitin and linezolid besides conventional drugs), respectively. The time to sputum-culture conversion and proportion of sputum-culture conversion in liquid broth were investigated to evaluate the efficacy and evaluation of safety by performing the classification of adverse events according to the Division of AIDS, National Institute of Allergy and Infectious Disease. Patients were followed for 18 months from baseline. Results. In the conventional regimen group, the sputum conversion rate at 18 months was 29.4% (10/34), and the median time until sputum conversion was 2 months (IQR, 1-2 mo). Furthermore, in the intensified regimen group, the sputum conversion rate was 81.3% (13/16), and the median time until sputum conversion was 1 month (IQR, 1-1 mo). Leukopenia and drug-induced hepatotoxicity occurred more frequently in the intensified regimen group in contrast with the conventional regimen group patients. However, only 1 adverse event in the intensified regimen group was classified as severe adverse event. Conclusions. The intensified regimen could improve sputum conversion of M. abscessus lung disease compared with conventional regimen, but close safety surveillance is necessary to monitor adverse events.

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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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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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