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

Moon, Sucbei; Park, Hye Yun; Kim, Su Young; Jhun, Byung Woo; Jeon, Kyeongman; Kim, Dae Hun; Huh, Hee Jae; Ki, Chang Seok; Lee, Nam Yong; Kim, Hong Kwan; Choi, Yong Soo; Kim, Young Tae; Lee, Seung Heon; Kim, Chang Ki; Shin, Sung Jae; Daley, Charles L.; Koh, Won Jung

doi:10.1128/aac.01240-16

Cited by 103 publications

(68 citation statements)

References 48 publications

(76 reference statements)

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“…Macrolides are the cornerstone drugs in the treatment of NTM-LD (4)(5)(6). Therefore, patients with macrolide-resistant MAC-LD (22)(23)(24)(25) or macrolide-resistant MABC-LD, including patients with lung disease caused by both isolates with intrinsic resistance and isolates with acquired resistance (26)(27)(28)(29)(30), have a very poor prognosis. In our study, salvage therapy with AMK inhalation was added to the existing (failing) regimens in all patients.…”

Section: Discussionmentioning

confidence: 99%

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Jhun

Yang

Moon

et al. 2018

Antimicrob Agents Chemother

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Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by complex (MABC) or complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology ( = 48, 62%), followed by MAC ( = 20, 26%) and mixed infections ( = 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) ( = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy ( < 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections ( = 0.009), a forced expiratory volume in 1 s of greater than 60% ( = 0.008), and the absence of macrolide resistance ( = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity ( = 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.

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Section: Discussionmentioning

confidence: 99%

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Jhun

Yang

Moon

et al. 2018

Antimicrob Agents Chemother

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“…8 Patients with macrolide-resistant MAC pulmonary disease have worse outcomes compared with those who have macrolidesusceptible infections. 9 Patient factors that may lead to macrolide resistance include high bacterial burden treated with suboptimal therapies, administration of macrolide monotherapy, and genetic mutations among the MAC strain. 9 It is important to maintain appropriate clinical and close laboratory monitoring while receiving this medication regimen.…”

Section: Discussionmentioning

confidence: 99%

51-Year-Old Man With Fever and Productive Cough

Herberts

Bourne

Escalante

2019

Mayo Clinic Proceedings

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“…effective therapy is essential to treat and prevent macrolide-resistant with MAC lung disease [140]. Antibiotic treatment associated with rifampicin, ethambutol and isoniazid or a quinolone with streptomycin or amikacin and surgical resection of disease can be used in macrolide-resistant MAC diseases [31,101,138,140]. Furthermore, the addition of moxifloxacin can improve the outcomes of patients with macrolide-resistant [141].…”

Section: Mycobacterium -Research and Developmentmentioning

confidence: 99%

Overview of Non Tuberculosis Mycobacterial Lung Diseases

Diseases¹

2018

Mycobacterium - Research and Development

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Nontuberculosis mycobacteria (NTM) are ubiquitous in nature and opportunistically infect different animals, including humans. Currently, NTM is emerging as an important cause of pulmonary infection among both immunocompromised and immunocompetent persons worldwide. The clinical relevance of pulmonary NTM varies among species while showing geographical heterogeneity in distribution as well as pathogenicity. The outcome of the respiratory NTM disease is a consequence of a complex interplay between microbial factors and host susceptibility. Furthermore, HIV infection, cystic fibrosis, cancer, underlying chronic lung disease and history of tuberculosis (TB) may be associated as risk factors for active nontuberculosis pulmonary diseases (NTMPD). The diagnosis of NTMPD requires the presence of symptoms, radiographic evidences, microscopic observations and definitive laboratory diagnostics. Lung infections resulted from a clinically significant NTM species should be treated with appropriate antimicrobial regimen. M. leprae and M. lepraemurium are uncultivable and require the intracellular milieu for survival and propagation [4]. The obligatory causative agents of the genus Mycobacterium, responsible for TB are classified into Mycobacterium tuberculosis complex (MTC). It comprises M. tuberculosis, M.bovis, M. africanum, M. microti [5], M. canettii [6], M. caprae [7], M. pinnipedii [8], M. mungi [9], M. orygis [10] and M. suricattae [11] species. M. tuberculosis, M. africanum, M. canettii and M. orygis cause TB primarily in human [4, 10], whereas M. bovis [12], M. microti [13], M. caprae [7] M. pinnipedii [8], M. mungi [9] and M. suricattae [11] infect cattle, domestic animals, goats, seals, mongooses and meerkats, respectively, and animal tuberculosis can also be zoonotic [14, 15]. However, geographical variation of the MTC species distribution has been identified. As an example, M. africanum is a common cause of human pulmonary TB (39%) as much as M. tuberculosis (55%) in West Africa [16]. In Ghana, 3% of pulmonary TB cases are represented by M. bovis, while 20% are M. africanum and 73% are M. tuberculosis [17].Other medically important mycobacteria such as M. avium, M. intracellulare complex, M. kansasii, M. marinum, M. fortuitum, M. chelonae complex, M. abscessus and M. scrofulaceum are known as nontuberculosis mycobacteria (NTM) species or atypical mycobacteria or mycobacteria other than tuberculosis (MOTT). They are responsible for diseases including lymphadenitis in children, chronic pulmonary diseases, skin and soft-tissue diseases and infections of the skeletal system [18]. NTM are ubiquitous in nature and are widely distributed in water, soil and animals. Among prevailing NTM species, only a few species have a clinical impact on humans as opportunistic pathogens [19]. M. avium complex (MAC), M. abscessus, M. kansasii, M. fortuitum, M. chelonae, M. szulgai, M. triviale and M. scrofulaceum are common NTM species that cause pulmonary diseases in human [20]. Additionally, M. riyadhense was recently proposed as a cau...

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

Cited by 103 publications

References 48 publications

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

51-Year-Old Man With Fever and Productive Cough

Overview of Non Tuberculosis Mycobacterial Lung Diseases

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