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

2018 ◽  
Vol 62 (10) ◽  
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.

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

2017 ◽  
Vol 61 (6) ◽  
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.

scholarly journals Intermittent Antibiotic Therapy for Recurrent Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Byung Woo Jhun ◽  
Seong Mi Moon ◽  
Su-Young Kim ◽  
Hye Yun Park ◽  
Kyeongman Jeon ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Lung Disease ◽  
Mycobacterium Avium ◽  
Previous Treatment ◽  
Intermittent Therapy ◽  
Oral Antibiotic ◽  
Content Type ◽  
Oral Antibiotic Therapy ◽  
Conversion Rates ◽  
Previously Treated

ABSTRACT Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy (n = 26) or intermittent therapy (n = 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.

scholarly journals Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease

2016 ◽  
Vol 60 (10) ◽  
pp. 6076-6083 ◽  
Author(s):  
Byeong-Ho Jeong ◽  
Kyeongman Jeon ◽  
Hye Yun Park ◽  
Seong Mi Moon ◽  
Su-Young Kim ◽  
...  
Keyword(s):  
Lung Disease ◽  
Mycobacterium Avium ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Mycobacterium Abscessus ◽  
Intermittent Therapy ◽  
Daily Regimen ◽  
Content Type ◽  
Intermittent Regimen

ABSTRACTMacrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment forMycobacterium aviumcomplex 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 AZMCmaxwas 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 forMycobacterium abscessuscomplex LD (MABC-LD) (250 mg of AZM daily,n= 55). The AZMCmaxwas 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, AZMCmaxwas 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 AZMCmaxwas common, whereas a higher AZMCmaxwas associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZMCmax. 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. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.)

scholarly journals Clinical Characteristics, Treatment Outcomes, and Resistance Mutations Associated with Macrolide-Resistant Mycobacterium avium Complex Lung Disease

2016 ◽  
Vol 60 (11) ◽  
pp. 6758-6765 ◽  
Author(s):  
Seong Mi Moon ◽  
Hye Yun Park ◽  
Su-Young Kim ◽  
Byung Woo Jhun ◽  
Hyun Lee ◽  
...  
Keyword(s):  
Lung Disease ◽  
Treatment Outcomes ◽  
Mycobacterium Avium ◽  
Macrolide Resistance ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Molecular Characteristics ◽  
Rrna Gene ◽  
Resistance Mutations ◽  
Content Type

ABSTRACTMacrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due toMycobacterium aviumcomplex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form.M. intracellularewas the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.

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

2017 ◽  
Vol 61 (10) ◽  
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.

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

2018 ◽  
Vol 62 (5) ◽  
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.

scholarly journals Effective Treatment of Mycobacterium avium subsp. hominissuis and Mycobacterium abscessus Species Infections in Macrophages, Biofilm, and Mice by Using Liposomal Ciprofloxacin

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James D. Blanchard ◽  
Valerie Elias ◽  
David Cipolla ◽  
Igor Gonda ◽  
Luiz E. Bermudez
Keyword(s):  
Effective Treatment ◽  
Mouse Models ◽  
Mycobacterium Avium ◽  
Nontuberculous Mycobacteria ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Number Of Individuals ◽  
Intranasal Instillation

ABSTRACT Nontuberculous mycobacteria (NTM) affect an increasing number of individuals worldwide. Infection with these organisms is more common in patients with chronic lung conditions, and treatment is challenging. Quinolones, such as ciprofloxacin, have been used to treat patients, but the results have not been encouraging. In this report, we evaluate novel formulations of liposome-encapsulated ciprofloxacin (liposomal ciprofloxacin) in vitro and in vivo. Its efficacy against Mycobacterium avium and Mycobacterium abscessus was examined in macrophages, in biofilms, and in vivo using intranasal instillation mouse models. Liposomal ciprofloxacin was significantly more active than free ciprofloxacin against both pathogens in macrophages and biofilms. When evaluated in vivo, treatment with the liposomal ciprofloxacin formulations was associated with significant decreases in the bacterial loads in the lungs of animals infected with M. avium and M. abscessus. In summary, topical delivery of liposomal ciprofloxacin in the lung at concentrations greater than those achieved in the serum can be effective in the treatment of NTM, and further evaluation is warranted.

scholarly journals Rifabutin Is Active against Mycobacterium abscessus in Mice

2019 ◽  
Vol 64 (2) ◽  
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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