European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights

Chalmers, James D.; Balavoine, C.; Castellotti, Paola; Hügel, Christian; Payet, A.; Wat, Dennis; Rohde, Gernot

doi:10.1183/23120541.00317-2020

Cited by 10 publications

(4 citation statements)

References 57 publications

(65 reference statements)

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“…In contrast to other studies that have identified MAC as the dominant NTM species [34,35], our study did not isolate any MAC species from the specimens. Instead, we observed a prevalence of species such as M. abscessus, M. chelonae, M. fortuitum, M. mucogenicum, M. gordonae, M. kansasii, and M. simiae in East Azerbaijan, Iran.…”

Section: Discussioncontrasting

confidence: 99%

Species and Genetic Diversity of Nontuberculous Mycobacteria (NTM) in Suspected Tuberculosis Cases in East Azerbaijan, Iran: A Cross-sectional Analysis

Roshdi Maleki

2024

Preprint

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IntroductionThe outbreak of nontuberculous mycobacterial (NTM) infections has increased worldwide, attracting attention in routine diagnostic settings, particularly among patients with suspected tuberculosis. This study aimed to acquire knowledge of NTM infections in patients with suspected tuberculosis and to evaluate the genetic diversity of the strains.MethodsIn this study, 230 clinical specimens were collected from suspected tuberculosis patients. Following decontamination with N-Acetyl-L-cysteine–sodium hydroxide (NALC-NaOH), the sediments of specimens were inoculated onto Löwenstein–Jensen medium and then incubated at 30°C for 8 weeks. The samples that yielded positive cultures underwent evaluation through sequencing conserved fragments ofIS6110andhsp65. For those samples that were not identified as part of theM. tuberculosiscomplex (MTC) byIS6110PCR, further analysis was conducted using PCR to detect fragments of thehsp65gene.ResultsTwenty-one NTM species were isolated from 230 clinical specimens (14 NTM from pulmonary specimens and 7 from extrapulmonary specimens). Among these, 12 (57.14%) were rapid-growing mycobacteria (RGM) and 9 (42.85%) were slow-growing mycobacteria (SGM). NoM. aviumcomplex (MAC) was identified in any of the specimens. Notably,M. kansasii, M. gordonae, andM. abscessusstrains exhibited significant genetic diversity.ConclusionsThe prevalence of infections attributed to nontuberculous species surpasses that of tuberculosis. These findings underscore the importance of exploring NTM species in individuals suspected of having TB.

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Section: Discussioncontrasting

confidence: 99%

Species and Genetic Diversity of Nontuberculous Mycobacteria (NTM) in Suspected Tuberculosis Cases in East Azerbaijan, Iran: A Cross-sectional Analysis

Roshdi Maleki

2024

Preprint

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“…A Phase II proof-of-concept study of inhaled NO in patients with NTM-PD has also been completed (trial registration: NCT03748992) and an open-label study of the at-home NO generator LungFit® GO is currently taking place (trial registration: NCT04685720). In vitro studies have shown potent antibacterial activity against M. abscessus following perfusion with NO in combination with clofazimine and amikacin [ 100 ]. Further studies are needed to assess the efficacy of NO against M. abscessus infection as part of combination therapy, and also its ability to reach bacteria sequestered in biofilms and macrophages.…”

Section: Methodsmentioning

confidence: 99%

Meeting the challenges of NTM-PD from the perspective of the organism and the disease process: innovations in drug development and delivery

Laan¹,

Snabilié²,

Obradović³

2022

Respir Res

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Non-tuberculous mycobacterial pulmonary disease (NTM-PD) poses a substantial patient, healthcare, and economic burden. Managing NTM-PD remains challenging, and factors contributing to this include morphological, species, and patient characteristics as well as the treatment itself. This narrative review focusses on the challenges of NTM-PD from the perspective of the organism and the disease process. Morphological characteristics of non-tuberculous mycobacteria (NTM), antimicrobial resistance mechanisms, and an ability to evade host defences reduce NTM susceptibility to many antibiotics. Resistance to antibiotics, particularly macrolides, is of concern, and is associated with high mortality rates in patients with NTM-PD. New therapies are desperately needed to overcome these hurdles and improve treatment outcomes in NTM-PD. Amikacin liposome inhalation suspension (ALIS) is the first therapy specifically developed to treat refractory NTM-PD caused by Mycobacterium avium complex (MAC) and is approved in the US, EU and Japan. It provides targeted delivery to the lung and effective penetration of macrophages and biofilms and has demonstrated efficacy in treating refractory MAC pulmonary disease (MAC-PD) in the Phase III CONVERT study. Several other therapies are currently being developed including vaccination, bacteriophage therapy, and optimising host defences. Newly developed antibiotics have shown potential activity against NTM-PD and include benzimidazole, delamanid, and pretomanid. Antibiotics commonly used to treat other infections have also been repurposed for NTM-PD, including clofazimine and bedaquiline. Data from larger-scale studies are needed to determine the potential of many of these therapies for treating NTM-PD.

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“…SGM include Mycobacterium avium complex (MAC), Mycobacterium chimaera , Mycobacterium kansasii , Mycobacterium malmoense , and Mycobacterium xenopi , whereas RGM comprise species from the Mycobacterium abscessus and Mycobacterium fortuitum complexes ( Alffenaar et al , 2021 ). In human infections, identifying NTM is crucial for determining clinically relevant species and the best treatment plan ( Chalmers et al , 2019 ; Mwangi et al , 2022a ).…”

Section: Introductionmentioning

confidence: 99%

Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya

et al. 2023

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Background: Non-tuberculous mycobacteria (NTM) treatment constitutes a macrolide-based antibiotic regimen in combination with aminoglycosides for Rapid-Growing Mycobacteria (RGM), and rifampicin for Slow-Growing Mycobacteria (SGM). Mutations in the anti-NTM drug target regions promote NTM evolution to mutant strains that are insusceptible to NTM drugs leading to treatment failure. We, therefore, described the mutation patterns of anti-NTM drug target genes including rrl, rrs, and rpoB in NTM isolates from Kenya. Methods: We carried out a cross-sectional study that included 122 NTM obtained from the sputum of symptomatic tuberculosis-negative patients in Kenya. All 122 NTM underwent targeted sequencing of the rrl gene. The 54 RGM were also sequenced for rrs, and the 68 SGM were sequenced for rpoB genes using ABI 3730XL analyzer. The obtained sequences were aligned to their wild-type reference sequences for each gene using Geneious then mutations were identified. Pearson chi-square at a 95% confidence interval tested the association of NTM to mutation patterns for each gene. Results: NTM harboring mutations associated with resistance to at least one of the antibiotics used in the macrolide-based therapy were 23% (28/122). Of these NTM, 10.4% (12/122) had mutations in the rrl gene with 58.3% (7/12) comprising RGM and 41.7% (5/12) being SGM. Mutation at position 2058 (A2058G, A2058C, A2058T) of the rrl gene was seen for 83.3% (10/12) of NTM, while 16.6% (2/12) harbored a A2059G mutation. Of the 54 RGM included for rrs characterization, 11.1% (6/54) exhibited mutations at position 1408(A1408G), while 14.7% (10/68) of the SGM had mutations in the rpoB gene at positions S531W, S531L, S531Y, F506L, E509H with M.gastri having multiple mutations at positions D516V, H526D and, S531F. Conclusion: We demonstrated a significant level of mutations associated with drug resistance for macrolides, aminoglycosides, and rifampicin in NTM isolated from symptomatic TB negative patients in Kenya.

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European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights

Cited by 10 publications

References 57 publications

Species and Genetic Diversity of Nontuberculous Mycobacteria (NTM) in Suspected Tuberculosis Cases in East Azerbaijan, Iran: A Cross-sectional Analysis

Species and Genetic Diversity of Nontuberculous Mycobacteria (NTM) in Suspected Tuberculosis Cases in East Azerbaijan, Iran: A Cross-sectional Analysis

Meeting the challenges of NTM-PD from the perspective of the organism and the disease process: innovations in drug development and delivery

Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya

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