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Journal of Cystic Fibrosis : Official... Mar 2020The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data...
BACKGROUND
The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking.
METHODS
This was a single center, retrospective study. MAC isolates had species identification with MLSA of rpoB and the 16S23S ITS region. Clinical data were compared between species.
RESULTS
Twenty-three people with CF and 57 MAC isolates were included. Infection with M. avium was the most common (65.2%). M. intracellulare was associated with higher rates of NTM disease, younger age, and steeper decline in lung function prior to infection.
CONCLUSIONS
We observed worse clinical outcomes in people with M. intracellulare infection relative to other MAC species. Further investigation of clinical outcomes of MAC infection among CF patients is warranted to better define the utility of species-level identification of MAC isolates in CF.
Topics: Adult; Anti-Bacterial Agents; Cystic Fibrosis; Female; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Outcome Assessment, Health Care; Prognosis; Respiratory Function Tests; Retrospective Studies; United States
PubMed: 31399327
DOI: 10.1016/j.jcf.2019.07.007 -
Scientific Reports Aug 2021To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) co-infections in HIV-negative patients. A... (Observational Study)
Observational Study
To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4T cells (P < 0.05). Factors including the ratio of the actual values to the cut-off values of AIGAs, WBC, N, HGB, CD4T cells, IgG, IgM, IgA, serum globulin, ESR, and CRP were taken as potential risk factors for TM and NTM co-infection. Most patients with TM and NTM co-infection had a missed diagnosis of one of the TM or NTM pathogens. The levels of AIGAs, WBC, N, ESR, and CRP in TM and NTM co-infections were remarkably higher than in mono-infection. High-titer AIGAs may be a potential risk factor and susceptibility factor for co-infection of TM and NTM in HIV-negative hosts.
Topics: Adult; Aged; Case-Control Studies; China; Coinfection; Cytokines; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prognosis; Retrospective Studies; Risk Factors; Talaromyces
PubMed: 34376749
DOI: 10.1038/s41598-021-95686-0 -
European Respiratory Review : An... Jun 2021Nontuberculous mycobacteria (NTM) are diverse microbial species encompassing commensals and pathogens with the ability to cause pulmonary disease in both immunocompetent... (Review)
Review
Nontuberculous mycobacteria (NTM) are diverse microbial species encompassing commensals and pathogens with the ability to cause pulmonary disease in both immunocompetent and immunocompromised individuals. In contrast to , which has seen a reduction in disease rates in developed countries, the incidence and prevalence of NTM disease is increasing. NTM are difficult to treat with standard antimicrobial regimens and may contain both virulence and antibiotic-resistance genes with potential for pathogenicity. With the advent of molecular techniques, it has been elucidated that these organisms do not reside in isolation and are rather part of a complex milieu of microorganisms within the host lung microbiome. Over the last decade, studies have highlighted the impact of the microbiome on host immunity, metabolism and cell-cell communication. This recognition of a broader community raises the possibility that the microbiome may disrupt the balance between infection and disease. Additionally, NTM disease progression and antimicrobial therapy may affect the healthy steady state of the host and function of the microbiome, contributing to further dysbiosis and clinical deterioration. There have been limited studies assessing how NTM may influence the relationship between microbiome and host. In this review, we highlight available studies about NTM and the microbiome, postulate on virulence mechanisms by which these microorganisms communicate and discuss implications for treatment.
Topics: Humans; Lung Diseases; Microbiota; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 34039671
DOI: 10.1183/16000617.0299-2020 -
Frontiers in Immunology 2021Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria... (Review)
Review
Autophagy is critically involved in host defense pathways through targeting and elimination of numerous pathogens autophagic machinery. Nontuberculous mycobacteria (NTMs) are ubiquitous microbes, have become increasingly prevalent, and are emerging as clinically important strains due to drug-resistant issues. Compared to (Mtb), the causal pathogen for human tuberculosis, the roles of autophagy remain largely uncharacterized in the context of a variety of NTM infections. Compelling evidence suggests that host autophagy activation plays an essential role in the enhancement of antimicrobial immune responses and controlling pathological inflammation against various NTM infections. As similar to Mtb, it is believed that NTM bacteria evolve multiple strategies to manipulate and hijack host autophagy pathways. Despite this, we are just beginning to understand the molecular mechanisms underlying the crosstalk between pathogen and the host autophagy system in a battle with NTM bacteria. In this review, we will explore the function of autophagy, which is involved in shaping host-pathogen interaction and disease outcomes during NTM infections. These efforts will lead to the development of autophagy-based host-directed therapeutics against NTM infection.
Topics: Animals; Anti-Bacterial Agents; Autophagy; Biological Evolution; Drug Resistance, Bacterial; Host-Pathogen Interactions; Humans; Immunity, Innate; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34552591
DOI: 10.3389/fimmu.2021.728742 -
Methods in Molecular Biology (Clifton,... 2023Mycobacterial infections, including tuberculosis, are a major health problem globally. Prevention and treatments of tuberculosis are challenging due to the poor efficacy...
Mycobacterial infections, including tuberculosis, are a major health problem globally. Prevention and treatments of tuberculosis are challenging due to the poor efficacy of the current vaccine and the emergence of drug-resistant strains. Therefore, it is critical to increase our basic understanding of mycobacterial virulence strategies as well as the host immune response during infection in the complex in vivo setting. While existing infection models provide valuable tools for investigating mycobacterial pathogenesis, they also exhibit limitations that can be addressed by the development of complementary models. Here we describe recent advances to the murine Mycobacterium marinum infection model, in which the bacteria produce a local infection restricted to the tail tissue. The M. marinum model has the advantage of mimicking some of the key hallmarks of human tuberculosis not replicated in the conventional murine Mycobacterium tuberculosis model, such as the formation of granulomas with central caseating necrosis and the spontaneous development of a latency-like stage. Moreover, the model is non-lethal and enables longitudinal analysis of disease development in live animals. In this chapter, we report protocols to prepare infected tissue samples for detailed and quantitative analysis of the immune response by flow cytometry, immunofluorescence microscopy, RT-qPCR, ELISA, and Western blot, as well as for the analysis of bacterial load and localization.
Topics: Animals; Mice; Humans; Mycobacterium Infections, Nontuberculous; Tuberculosis; Mycobacterium tuberculosis; Virulence; Mycobacterium marinum; Zebrafish
PubMed: 37258977
DOI: 10.1007/978-1-0716-3243-7_21 -
Stem Cell Reports Sep 2022Human macrophages are a natural host of many mycobacterium species, including Mycobacterium abscessus (M. abscessus), an emerging pathogen affecting immunocompromised...
Human macrophages are a natural host of many mycobacterium species, including Mycobacterium abscessus (M. abscessus), an emerging pathogen affecting immunocompromised and cystic fibrosis patients with few available treatments. The search for an effective treatment is hindered by the lack of a tractable in vitro intracellular infection model. Here, we established a reliable model for M. abscessus infection using human pluripotent stem cell-derived macrophages (hPSC-macrophages). hPSC differentiation permitted reproducible generation of functional macrophages that were highly susceptible to M. abscessus infection. Electron microscopy demonstrated that M. abscessus was present in the hPSC-macrophage vacuoles. RNA sequencing analysis revealed a time-dependent host cell response, with differing gene and protein expression patterns post-infection. Engineered tdTOMATO-expressing hPSC-macrophages with GFP-expressing mycobacteria enabled rapid image-based high-throughput analysis of intracellular infection and quantitative assessment of antibiotic efficacy. Our study describes the first to our knowledge hPSC-based model for M. abscessus infection, representing a novel and accessible system for studying pathogen-host interaction and drug discovery.
Topics: Humans; Macrophages; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Pluripotent Stem Cells
PubMed: 35985333
DOI: 10.1016/j.stemcr.2022.07.013 -
Lung Feb 2021E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well...
INTRODUCTION
E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well understood. However, it is speculated that certain substances such as Vitamin E Acetate (VEA), particularly in marijuana containing vape cartridges may result in lung injury and lead to respiratory dysfunction. EVALI is often seen in the absence of infections, but it has been found to be associated with both fungal and bacterial infections. Like EVALI, nontuberculous mycobacteria (NTM) pulmonary disease is also on the rise, but is primarily reported in immunocompromised individuals. Here, we present three immunocompetent individuals wherein pulmonary NTM infection co-occurred with vaping.
METHODS
Medical information including patient history, laboratory, and radiograph reports were abstracted from electronic medical records from participating institutions located in the Bronx, NY, Philadelphia, PA, and Lexington, KY.
RESULTS
All three cases were otherwise immunocompetent individuals with a significant history of vaping either nicotine and/or marijuana containing products. The pathogens isolated include Mycobacterium avium complex, M. xenopi, and M. gordonae. All three patients were treated for NTM.
CONCLUSION
There is little reported on the association between vaping and NTM. It is possible that vaping may have rendered these individuals to be more susceptible to NTM colonization and infection. The possible mechanisms of vaping lung injury and pulmonary NTM are discussed.
Topics: Adolescent; Adult; Antitubercular Agents; Asthma; Electronic Nicotine Delivery Systems; Female; Humans; Immunocompetence; Lung; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Retrospective Studies; Tomography, X-Ray Computed; Vaping; Young Adult
PubMed: 33423072
DOI: 10.1007/s00408-020-00414-6 -
BMJ Case Reports Nov 2021A gentleman in his 60s with end-stage kidney disease status post kidney transplantation on prednisone and tacrolimus presented with generalised weakness for 7 days,...
A gentleman in his 60s with end-stage kidney disease status post kidney transplantation on prednisone and tacrolimus presented with generalised weakness for 7 days, associated with altered mental status. Investigations revealed pancytopenia, acute kidney injury, hypercalcaemia, decreased parathyroid hormone (PTH) and normal calcitriol levels. CT of the chest showed multifocal lung opacities suspicious for malignancy. Bronchoscopy with biopsy yielded no malignant cells, and bronchoalveolar lavage specimens grew The patient was treated with bisphosphonates, calcitonin and antibiotics for non-tuberculous mycobacteria pulmonary infection, with improvement in serum calcium levels, and was discharged after 5 weeks of hospitalisation.The work-up for hypercalcaemia begins with PTH measurement, and low PTH levels are consistent with malignancy, immobilisation and granulomatous diseases. Hypercalcaemia in the lattermost is classically caused by overproduction of calcitriol by activated macrophages. However, there are case reports of mycobacterial infections with hypercalcaemia despite normal calcitriol levels, supporting the existence of an additional mechanism of hypercalcaemia in granulomatous infections.
Topics: Aged; Calcium; Humans; Hypercalcemia; Lung; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Parathyroid Hormone
PubMed: 34848413
DOI: 10.1136/bcr-2021-245800 -
Frontiers in Cellular and Infection... 2022To evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the...
OBJECTIVE
To evaluate the performance and validate the diagnostic value of a nucleotide matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) with the analysis process optimized in identification of mycobacterium species.
METHODS
The optimized analysis process was used for mycobacterial identification in the nucleic MALDI-TOF-MS. 108 samples were used for assessing the performance of nucleic MALDI-TOF-MS, including 25 reference standards, 37 clinical isolates, 37 BALF, and 9 plasmids. The BALF of 38 patients suspected of pulmonary mycobacterial infection was collected for validation. Clinical etiological diagnosis was used as the gold standard to evaluate the diagnostic value of nucleotide MALDI-TOF-MS.
RESULTS
The sensitivity, specificity, and accuracy of the nucleotide MALDI-TOF-MS in mycobacterial identification were 96.91%, 100% and 97.22%, respectively, and the limit of detection for mycobacterium tuberculosis (MTB) was 50 bacteria/mL. Among 38 patients suspected of pulmonary mycobacterial infection, 33 were diagnosed with pulmonary tuberculosis infection, and 5 with non-mycobacterial infection. In clinical validation, the positive rates of MALDI-TOF-MS, Xpert MTB/RIF, culture and AFS in BALF of patients diagnosed with tuberculosis infection were 72.7%, 63.6%, 54.5% and 27.3%, respectively. The sensitivity/specificity of MALDI-TOF-MS, Xpert, culture and AFS in diagnosing MTB were 72.7%/100%, 63.6%/100%, 54.5%/100%, 27.3%/100%, with the areas under the curve of 0.864, 0.818, 0.773, and 0.636, respectively.
CONCLUSION
Optimized nucleotide MALDI-TOF-MS has satisfactory sensitivity, specificity and low LOD in the identification of mycobacteria, which may serve as a potential assay for mycobacterial identification.
Topics: Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Nucleotides; Mycobacterium tuberculosis; Tuberculosis; Mycobacterium Infections, Nontuberculous
PubMed: 36530426
DOI: 10.3389/fcimb.2022.1079184 -
International Journal of... 2022Nontuberculosis mycobacterium (NTM) is the emerging group of organisms being recognized as etiological agents for diverse clinical conditions such as lymphadenitis,...
BACKGROUND
Nontuberculosis mycobacterium (NTM) is the emerging group of organisms being recognized as etiological agents for diverse clinical conditions such as lymphadenitis, cutaneous, and pulmonary or disseminated lesions. Diverse background patients can acquire these infections such as immunocompetent, immunocompromised patients, or postoperative settings. Rapid addition of newer strains to this group necessitates heightened suspicion in the clinical settings. Specific requirements for cultures, biochemical testing, and molecular methods are needed to diagnose these organisms.
METHODS
The prospective study conducted at Nizam's Institute of Medical Sciences from January 2019 to December 2021 using various clinical samples using molecular techniques such as line probe assay and hsp-65 gene sequencing to discover new NTM species. The management is challenging since it requires prolonged treatment, multiple drugs, drug resistance, and individualization of treatment in the combination of surgery if needed. In this article, we describe three different NTM species which were not reported in India and highlight to consider these organisms in adequate clinical situation.
RESULTS
Mycobacterium iranicum is a rare strain with quick growth and scotochromogenic colonies that are orange-colored. Eight distinct strains were discovered in clinical samples from six different countries: Two each from Iran, Italy, Greece, the Netherlands, Sweden, and the United States. Two of the strains were recovered from cerebrospinal fluid, which is unusual. Mycobacterium species AW6 is an unidentified and unclassified Mycobacterium according to NCBI taxonomy. Mycobacteria malmoense has been linked to lymphadenitis, notably cervical adenitis in children, and pulmonary infection in the majority of cases. Using Line Probe Assay and hsp-65 gene sequencing, novel and uncommon species of NTM were detected from a clinical samples, including sputum and tissue.
CONCLUSION
We report three unusual species of NTMs: M. iranicum, M. species-AW6, and M. malmoense for the first time in India. Novel and rare emerging species of NTMs need to be considered in diverse clinical situations for appropriate therapy and good clinical outcomes.
Topics: Child; Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Prospective Studies; Sputum; Lymphadenitis
PubMed: 36510929
DOI: 10.4103/ijmy.ijmy_175_22