Non‐tuberculous mycobacterial infection among lung transplant recipients: a 15‐year cohort study

Knoll, Bettina M.; Kappagoda, Shanthi; Gill, Ritu R.; Goldberg, Hilary J.; Boyle, K.; Baden, Lindsey R.; Fuhlbrigge, Anne L.; Marty, Francisco M.

doi:10.1111/j.1399-3062.2012.00753.x

Cited by 118 publications

(92 citation statements)

References 23 publications

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“…Lung transplant, although still somewhat of a contraindication, may be one potential treatment for lung NTM infection (24). Indeed, lung transplantation has been performed in patients with cystic fibrosis who carried MAC (25,26). Although it should be noted that posttransplant immunosuppressive management together with antimycobacterials lacking competent macrolide ability raises the possibility of reemergence of resistant MAC infections in the donor lung.…”

Section: Discussionmentioning

confidence: 99%

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

et al. 2016

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The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated. The nontuberculous mycobacteria (NTM) are ubiquitous microorganisms found in various environments. They are capable of causing miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. It is noteworthy that the prevalence of lung NTM is increasing throughout the world (1, 2). Whereas NTM diversity in clinical manifestations and geographic distribution has been well documented, Mycobacterium avium and Mycobacterium intracellulare, collectively referred to as the Mycobacterium avium-intracellulare complex (MAC), are frequently isolated from such patients in most countries (3).To date, knowledge of the pathogenic role of MAC strains in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. Clarithromycin is a ribosome-targeting macrolide antibiotic that interacts with a bacterial 23S rRNA hairpin-like structure in domain II and the peptidyl transferase loop in domain V (4, 5). Additionally, clarithromycin is the only agent for which susceptibility testing has high clinical efficacy. Therefore, management of clarithromycin-resistant MAC isolates from advanced lung NTM is an emerging concern. It is worth noting that multidrug therapy containing clarithromycin as the key drug is now a mandatory implementation to prevent resistance.Other s...

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Section: Discussionmentioning

confidence: 99%

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

et al. 2016

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“…In a single-centre cohort study of 237 lung transplant recipients, 53 (22%) isolated NTM 328. The the most common organism was MAC (70%), followed by M. abscessus (9%) and M. gordonae (8%).…”

Section: Section 12d: What Antibiotic Regimen Should Be Used To Treatmentioning

confidence: 99%

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

Haworth

Banks

Capstick

et al. 2017

Thorax

592

679

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“…Some of them are potential pathogens causing infections not only in immunocompromised patients but also in normal hosts (1,2). In general, a number of NTM are slowly growing organisms, and laboratory diagnosis usually takes Ͼ5 days.…”

mentioning

confidence: 99%

Advantages of Using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry as a Rapid Diagnostic Tool for Identification of Yeasts and Mycobacteria in the Clinical Microbiological Laboratory

et al. 2013

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Non‐tuberculous mycobacterial infection among lung transplant recipients: a 15‐year cohort study

Cited by 118 publications

References 23 publications

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

PCR-Based Rapid Identification System Using Bridged Nucleic Acids for Detection of Clarithromycin-Resistant Mycobacterium avium-M. intracellulare Complex Isolates

British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

Advantages of Using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry as a Rapid Diagnostic Tool for Identification of Yeasts and Mycobacteria in the Clinical Microbiological Laboratory

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