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American Journal of Respiratory and... May 2022Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, with...
Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program. To systematically investigate healthcare-associated transmission and/or acquisition of NTM to determine similarity among respiratory and environmental isolates, and to compare home residence watershed mapping among pwCF having genetically similar NTM isolates. Whole-genome sequencing of NTM isolates from 80 pwCF was conducted to identify genetically similar isolate clusters (⩽30 SNP differences). Epidemiology, comparison of respiratory and environmental isolates, and home residence watershed mapping were analyzed. Whole-genome sequencing analysis revealed 11 clusters of NTM [6 subspecies (ssp.) , 1 ssp. , 2 , and 2 ] among pwCF. Epidemiologic investigation demonstrated opportunities for healthcare-associated transmission in two and two clusters. Respiratory and healthcare environmental isolate comparisons revealed no genetic similarity. Individuals comprising one cluster, with no plausible healthcare-associated transmission, resided in the same watershed. This study suggests healthcare-associated transmission of is rare and includes a report of potential healthcare-associated transmission of among pwCF. One cluster possibly had common acquisition arising from residing in the same watershed. The presence of genetically similar isolates is insufficient to demonstrate healthcare-associated NTM transmission. Standardizing epidemiologic investigation, combined with environmental sampling and watershed analysis, will improve understanding of the frequency and nature of healthcare-associated NTM transmission among pwCF.
Topics: Adult; Colorado; Cystic Fibrosis; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Nontuberculous Mycobacteria
PubMed: 35085056
DOI: 10.1164/rccm.202108-1911OC -
Frontiers in Immunology 2022Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms capable of a wide range of infections that primarily involve the lymphatic system and the... (Review)
Review
Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms capable of a wide range of infections that primarily involve the lymphatic system and the lower respiratory tract. In recent years, cases of lung infection sustained by NTM have been steadily increasing, due mainly to the ageing of the population with underlying lung disease, the enlargement of the cohort of patients undergoing immunosuppressive medications and the improvement in microbiologic diagnostic techniques. However, only a small proportion of individuals at risk ultimately develop the disease due to reasons that are not fully understood. A better understanding of the pathophysiology of NTM pulmonary disease is the key to the development of better diagnostic tools and therapeutic targets for anti-mycobacterial therapy. In this review, we cover the various types of interactions between NTM and lymphoid effectors of innate and adaptive immunity. We also give a brief look into the mechanism of immune exhaustion, a phenomenon of immune dysfunction originally reported for chronic viral infections and cancer, but recently also observed in the setting of mycobacterial diseases. We try to set the scene to postulate that a better knowledge of immune exhaustion can play a crucial role in establishing prognostic/predictive factors and enabling a broader investigation of immune-modulatory drugs in the experimental treatment of NTM pulmonary disease.
Topics: Humans; Lung Diseases; Lymphocytes; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Pneumonia, Bacterial
PubMed: 35837393
DOI: 10.3389/fimmu.2022.927049 -
The Cochrane Database of Systematic... Jun 2020Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous...
BACKGROUND
Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.
OBJECTIVES
The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020. We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019.
SELECTION CRITERIA
Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
MAIN RESULTS
One completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
AUTHORS' CONCLUSIONS
This review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.
Topics: Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Nontuberculous Mycobacteria
PubMed: 32521055
DOI: 10.1002/14651858.CD010004.pub5 -
Paediatric Respiratory Reviews Jun 2023Nontuberculous mycobacteria (NTM) can cause severe pulmonary disease in people with cystic fibrosis (pwCF). These infections present unique challenges for diagnosis and... (Review)
Review
Nontuberculous mycobacteria (NTM) can cause severe pulmonary disease in people with cystic fibrosis (pwCF). These infections present unique challenges for diagnosis and treatment, prompting a recent interest in understanding NTM transmission and pathogenesis during chronic infection. Major gaps remain in our knowledge regarding basic pathogenesis, immune evasion strategies, population dynamics, recombination potential, and the evolutionary implications of host and antibiotic pressures of long-term NTM infections in pwCF. Phylogenomic techniques have emerged as an important tool for tracking global patterns of transmission and are beginning to be used to ask fundamental biological questions about adaptation to the host during pathogenesis. In this review, we discuss the burden of NTM lung disease (NTM-LD), highlight the use of phylogenomics in NTM research, and address the clinical implications associated with these studies.
Topics: Humans; Cystic Fibrosis; Phylogeny; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Respiratory Tract Infections
PubMed: 36828670
DOI: 10.1016/j.prrv.2023.02.001 -
Emerging Infectious Diseases Jul 2022Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP...
Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.
Topics: Humans; Lung Diseases; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 35731181
DOI: 10.3201/eid2807.212320 -
The Journal of Antimicrobial... Apr 2024Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant...
BACKGROUND
Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing worldwide, with Mycobacterium avium complex (MAC) and Mycobacterium abscessus as the predominant pathogens. Current treatments are poorly tolerated and modestly effective, highlighting the need for new treatments. SPR719, the active moiety of the benzimidazole prodrug SPR720, inhibits the ATPase subunits of DNA gyrase B, a target not exploited by current antibiotics, and therefore, no cross-resistance is expected with standard-of-care (SOC) agents.
OBJECTIVES
To evaluate the in vitro activity of SPR719 against MAC and M. abscessus clinical isolates, including those resistant to SOC agents, and in vivo efficacy of SPR720 in murine non-tuberculous mycobacteria (NTM) pulmonary infection models.
METHODS
NTM isolates were tested for susceptibility to SPR719. Chronic C3HeB/FeJ and severe combined immunodeficient murine models of pulmonary infection were used to assess efficacy of SPR720 against MAC and M. abscessus, respectively.
RESULTS
SPR719 was active against MAC (MIC90, 2 mg/L) and M. abscessus (MIC90, 4 mg/L) clinical isolates. Efficacy of SPR720 was demonstrated against MAC pulmonary infection, both as a monotherapy and in combination with SOC agents. SPR720 monotherapy exhibited dose-dependent reduction in bacterial burden, with the largest reduction observed when combined with clarithromycin and ethambutol. Efficacy of SPR720 was also demonstrated against M. abscessus pulmonary infection where monotherapy exhibited a dose-dependent reduction in bacterial burden with further reductions detected when combined with SOC agents.
CONCLUSIONS
In vitro activity of SPR720 against common NTM pathogens and efficacy in murine infections warrant the continued clinical evaluation of SPR720 as a new oral option for the treatment of NTM-PD.
Topics: Humans; Animals; Mice; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Disease Models, Animal; Mycobacterium avium Complex; Anti-Bacterial Agents; Lung Diseases; Pneumonia
PubMed: 38394463
DOI: 10.1093/jac/dkae046 -
Journal of Clinical Microbiology Jan 2020infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different....
infection and nontuberculous mycobacteria (NTM) infections exhibit similar clinical symptoms; however, the therapies for these two types of infections are different. Therefore, the rapid and accurate identification of and NTM species is very important for the control of tuberculosis and NTM infections. In the present study, a Cas12a/guide RNA (gRNA)-based platform was developed to identify and most NTM species. By designing species-specific gRNA probes targeting the sequence, a Cas12a/gRNA-based platform successfully identified and six major NTM species (, , , , , and ) without cross-reactivity. In a blind assessment, a total of 72 out of 73 clinical isolates were correctly identified, which is consistent with previous sequencing results. These results suggest that the Cas12a/gRNA-based platform is a promising tool for the rapid, accurate, and cost-effective identification of both and NTM species.
Topics: Bacterial Proteins; CRISPR-Associated Proteins; CRISPR-Cas Systems; Endodeoxyribonucleases; Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; RNA Probes; RNA, Guide, CRISPR-Cas Systems; RNA, Ribosomal, 16S; Sensitivity and Specificity; Tuberculosis
PubMed: 31723010
DOI: 10.1128/JCM.01368-19 -
Microbiology (Reading, England) May 2020is so far the most thermophilic among mycobacteria as it grows optimally at 50 °C and up to 65 °C in a glycerol-based medium, as verified in this study. Since...
is so far the most thermophilic among mycobacteria as it grows optimally at 50 °C and up to 65 °C in a glycerol-based medium, as verified in this study. Since this and other nontuberculous mycobacteria (NTM) thrive in diverse natural and artificial environments, from where they may access and infect humans, we deemed essential to probe resistance to heat, a strategy routinely used to control microbial growth in water-supply systems, as well as in the food and drink industries. In addition to possibly being a threat in its own right in rare occasions, is also a good surrogate for studying other NTM species more often associated with opportunistic infection, namely and as well as their strictly pathogenic counterparts and . In this regard, this thermophilic species is likely to be useful as a source of stable proteins that may provide more detailed structures of potential drug targets. Here, we investigate growth at near-pasteurization temperatures and at different pHs and also characterize its thermostable glucosyl-3-phosphoglycerate synthase (GpgS), an enzyme considered essential for growth and associated with both nitrogen starvation and thermal stress in different NTM species.
Topics: Bacterial Proteins; DNA, Bacterial; Glucosyltransferases; Hydrogen-Ion Concentration; Mycobacteriaceae; Nontuberculous Mycobacteria; Pasteurization; Temperature
PubMed: 32100712
DOI: 10.1099/mic.0.000898 -
International Journal of... 2023Nontuberculous mycobacterial (NTM) pulmonary disease (PD) has rapidly increased globally. The characteristics and comparison of rapidly growing mycobacteria PD (RGM-PD)...
BACKGROUND
Nontuberculous mycobacterial (NTM) pulmonary disease (PD) has rapidly increased globally. The characteristics and comparison of rapidly growing mycobacteria PD (RGM-PD) and slowly growing mycobacteria PD (SGM-PD) are still unclear.
METHODS
Our study enrolled 31 NTM-PD patients. Clinical data, including baseline, symptoms, underlying disease, laboratory tests, metagenomic next-generation sequencing (mNGS) results, radiological images, treatment, and outcome were recorded and analyzed.
RESULTS
Of the 31 patients with NTM-PD, 22 patients were female and 9 were male. It included 11 RGM-PD and 20 SGM-PD. There was no difference in age (P = 0.425) and body mass index (P = 0.152) between the two groups. The common respiratory diseases in prevalence included bronchiectasis and chronic obstructive pulmonary disease. Three patients had positive results of T-SPOT tuberculosis (TB), and none had positive Xpert-Mycobacterium tuberculosis/rifampin results. On admission, patients were symptomatic and included cough/sputum production, fever, weight loss, fatigue, and hemoptysis. In comparison to RGM-PD, patients with SGM-PD had a greater chance of experiencing fatigue (P = 0.012). No significance was found in serum biomarkers between RGM and SGM-PD, including CD4/CD8 ratio, white blood cells, neutrophils, lymphocytes, procalcitonin, ferritin, C-reactive protein, and erythrocyte sedimentation rate. No liver or kidney impairment was found. Patients with RGM-PD were more likely to have right lower lobe (RLL) impairment (P = 0.021) and a cavity characteristic (P = 0.012). All 31 cases had positive mNGS results. The duration of mNGS was shorter than conventional methods (3.4 ± 0.7 vs. 26.4 ± 20.9, P < 0.001).
CONCLUSIONS
Patients with SGM-PD were more likely to experience fatigue. The cavity and RLL involvement were more frequent in the RGM-PD. mNGS increases the identification of NTM specimens and complements the capabilities of conventional methods.
Topics: Humans; Male; Female; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Bronchiectasis; Hemoptysis; Mycobacterium tuberculosis
PubMed: 37721240
DOI: 10.4103/ijmy.ijmy_145_23 -
The Journal of Medical Investigation :... 2021The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical... (Review)
Review
The incidence rate of pulmonary nontuberculous mycobacterial disease (PNTMD) in Japan is the highest among major industrialized nations. Although the typical clinical course and radiological manifestations of PNTMD are different from those of pulmonary tuberculosis (TB), confusion about these mycobacterial diseases leads to a diagnostic pitfall. Diagnostic challenges include the coexistence of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM), false positives for NTM in MTB nucleic acid amplification tests, microbial substitution, and abnormal radiological manifestations caused by NTM. Features of extrapulmonary NTM diseases, such as pleurisy, vertebral osteomyelitis, and disseminated disease, are different from the corresponding tuberculous diseases. Moreover, the immunological background of the patient (status of human immunodeficiency virus infection with or without antiviral therapy, continuation or discontinuation of immunosuppressive therapy, use of immune checkpoint inhibitor, pregnancy and delivery, etc.) influences the pathophysiology of mycobacterial diseases. This review describes the varying clinical presentations of NTM disease with emphasis on the differences from TB. J. Med. Invest. 68 : 220-227, August, 2021.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 34759134
DOI: 10.2152/jmi.68.220