Macrolide-Resistant <i>Mycobacterium avium</i> Complex Lung Disease: Analysis of 102 Consecutive Cases

Morimoto, Kozo; Namkoong, Ho; Hasegawa, Naoki; Nagao, Taku; Morino, Eriko; Shiraishi, Yuji; Ogawa, Kenji; Izumi, Kiyohiko; Jin, Tao; Yoshiyama, Takashi; Hoshino, Yoshihiko; Matsuda, Shinji; Hayashi, Yuta; Sasaki, Yuka; Ishii, Makoto; Kurashima, Atsuyuki; Nishimura, Tomoyasu; Betsuyaku, Tomoko; Goto, Hajime

doi:10.1513/annalsats.201604-246oc

Cited by 113 publications

(90 citation statements)

References 30 publications

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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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“…The NTM species of the Mycobacterium avium complex (MAC ), M. kansasii and M. abscessus have been implicated in pulmonary human disease (McShane & Glassroth, ), with MAC being a principal culprit of clinically diagnosed pulmonary NTM infections (Mirsaeidi, Farshidpour, Ebrahimi, Aliberti, & Falkinham, ; Prevots & Marras, ; Schluger, ). Despite M. avium pathogenesis not being entirely delineated in humans, it is arguably one of the most characterized and studied NTM (Appelberg, ; Appelberg et al, ; Bermudez et al, ; Field, Fisher, & Cowie, ; Johnson & Odell, ; Morimoto et al, ; Stout et al, ). Typical contraction of M. avium stems from the inhalation or ingestion of aerosolized mycobacteria or mycobacterial droplets (Appelberg, ; Appelberg et al, ; Bermudez et al, ).…”

Section: Introductionmentioning

confidence: 99%

Nontuberculous mycobacterium M. avium infection predisposes aged mice to cardiac abnormalities and inflammation

et al. 2019

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Biological aging dynamically alters normal immune and cardiac function, favoring the production of pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α) and increased instances of cardiac distress. Cardiac failure is the primary reason for hospitalization of the elderly (65+ years). The elderly are also increasingly susceptible to developing chronic bacterial infections due to aging associated immune abnormalities. Since bacterial infections compound the rates of cardiac failure in the elderly, and this phenomenon is not entirely understood, the interplay between the immune system and cardiovascular function in the elderly is of great interest. Using Mycobacterium avium, an opportunistic pathogen, we investigated the effect of mycobacteria on cardiac function in aged mice. Young (2–3 months) and old (18–20 months) C57BL/6 mice were intranasally infected with M. avium strain 104, and we compared the bacterial burden, immune status, cardiac electrical activity, pathology, and function of infected mice against uninfected age‐matched controls. Herein, we show that biological aging may predispose old mice infected with M. avium to mycobacterial dissemination into the heart tissue and this leads to cardiac dysfunction. M. avium infected old mice had significant dysrhythmia, cardiac hypertrophy, increased recruitment of CD45+ leukocytes, cardiac fibrosis, and increased expression of inflammatory genes in isolated heart tissue. This is the first study to report the effect of mycobacteria on cardiac function in an aged model. Our findings are critical to understanding how nontuberculous mycobacterium (NTM) and other mycobacterial infections contribute to cardiac dysfunction in the elderly population.

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“…In our study, bacteriostatic activity has been demonstrated against M. tuberculosis strains and slow grower mycobacteria ( M. avium ) showing growth after clearance of the compounds. The activity at very low doses of selected compounds ( PS4 , PS9 , PS14 , and PS18 ) on M. avium could be of potential interest as this mycobacterium infects immunodepressed patients and resistance to macrolides is increasing . Moderate bacteriostatic activity has been previously shown for usnic acid, and some derivatives .…”

Section: Discussionmentioning

confidence: 99%

Synthesis and antimycobacterial activity of (+)‐usnic acid conjugates

Cirillo

Borroni

Festoso

et al. 2018

Archiv der Pharmazie

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New therapeutics are urgently needed to fight tuberculosis and mycobacteria-related diseases that are a major health hazard especially in poor countries. Natural products have been the source of important antitubercular drugs in the past and still need to receive attention as a potent reservoir of chemical structures. Fifteen known and two new (+)-usnic acid (a benzofurandione formerly isolated from lichens) enamines and hydrazones are here described and tested against sensitive and multidrug-resistant strains of mycobacteria. Among several (+)-usnic acid conjugates, PS14 and PS18 showed potent activity against both susceptible and resistant Mycobacterium tuberculosis strains (MIC values of 1-32 and 2-32 mg/L, respectively) comparable with MIC of other antitubercular drugs already in use for tuberculosis treatment.

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Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102 Consecutive Cases

Cited by 113 publications

References 30 publications

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacterium M. avium infection predisposes aged mice to cardiac abnormalities and inflammation

Synthesis and antimycobacterial activity of (+)‐usnic acid conjugates

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