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Biofouling Apr 2021The role of biofilms in pathogenicity and treatment strategies is often neglected in mycobacterial infections. In recent years, the emergence of nontuberculous... (Review)
Review
The role of biofilms in pathogenicity and treatment strategies is often neglected in mycobacterial infections. In recent years, the emergence of nontuberculous mycobacterial infections has necessitated the development of novel prophylactic strategies and elucidation of the mechanisms underlying the establishment of chronic infections. More importantly, the question arises whether members of the complex can form biofilms and contribute to latent tuberculosis and drug resistance because of the long-lasting and recalcitrant nature of its infections. This review discusses some of the molecular mechanisms by which biofilms could play a role in infection or pathological events in humans.
Topics: Biofilms; Humans; Mycobacterium; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 34024206
DOI: 10.1080/08927014.2021.1925886 -
BMC Infectious Diseases Mar 2024Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been...
BACKGROUND
Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs.
METHODS
We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae.
RESULTS
Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast.
CONCLUSIONS
The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas.
Topics: United States; Humans; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Mycobacterium abscessus; Laboratories; Mycobacterium bovis; Opportunistic Infections
PubMed: 38448840
DOI: 10.1186/s12879-024-09059-9 -
Frontiers in Immunology 2022complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental... (Review)
Review
complex (MAC) is the main causative agent of infectious diseases in humans among nontuberculous mycobacteria (NTM) that are ubiquitous organisms found in environmental media such as soil as well as in domestic and natural waters. MAC is a primary causative agent of NTM-lung disease that threaten immunocompromised or structural lung disease patients. The incidence and the prevalence of infection have been reduced, while MAC infections and mortality rates have increased, making it a cause of global health concern. The emergence of drug resistance and the side effects of long-term drug use have led to a poor outcome of treatment regimens against MAC infections. Therefore, the development of host-directed therapy (HDT) has recently gained interest, aiming to accelerate mycobacterial clearance and reversing lung damage by employing the immune system using a novel adjuvant strategy to improve the clinical outcome of MAC infection. Therefore, in this review, we discuss the innate immune responses that contribute to MAC infection focusing on macrophages, chief innate immune cells, and host susceptibility factors in patients. We also discuss potential HDTs that can act on the signaling pathway of macrophages, thereby contributing to antimycobacterial activity as a part of the innate immune response during MAC infection. Furthermore, this review provides new insights into MAC infection control that modulates and enhances macrophage function, promoting host antimicrobial activity in response to potential HDTs and thus presenting a deeper understanding of the interactions between macrophages and MACs during infection.
Topics: Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Macrophages; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Lung Diseases
PubMed: 36505429
DOI: 10.3389/fimmu.2022.931876 -
Tuberculosis (Edinburgh, Scotland) Sep 2022Non-tuberculous mycobacteria are a heterogeneous group of environmental bacteria and other than the well-known Mycobacterium tuberculosis complex and Mycobacterium...
Non-tuberculous mycobacteria are a heterogeneous group of environmental bacteria and other than the well-known Mycobacterium tuberculosis complex and Mycobacterium leprae. They could cause localized or disseminated infections. Mycobacterium chelonae and Mycobacterium fortuitum are among the most clinically relevant non-tuberculous mycobacteria species. The infections treatment is complex since they are resistant to antituberculosis drugs and the biofilm formation makes them impermeable to several antibiotics. Antimicrobial photodynamic therapy (aPDT) constitutes an alternative to eliminate pathogens, principally those antimicrobials resistant. Among explored photosensitizers, phthalocyanines are considered excellent, but with a disadvantage: a lack solubility in aqueous media. Consequently, several nanocarriers have been studied in the last years. In this work, a Zn-phthalocyanine into liposomes was evaluated to photoinactivate M. fortuitum and M. chelonae. The results show a higher photodynamic activity of ZnPc into liposomes respect to solution. Furthermore, M. fortuitum was more sensible to aPDT than M. chelonae.
Topics: Antitubercular Agents; Humans; Isoindoles; Liposomes; Mycobacterium Infections, Nontuberculous; Mycobacterium chelonae; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Organometallic Compounds; Photosensitizing Agents; Zinc Compounds
PubMed: 35977438
DOI: 10.1016/j.tube.2022.102247 -
Annali Dell'Istituto Superiore Di Sanita 2023Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to...
INTRODUCTION
Nontuberculous mycobacteria (NTM) are environmental mycobacteria which may cause pulmonary and extrapulmonary diseases. These organisms are difficult to treat due to their intrinsic drug-resistance. In Italy, no major nationwide study on NTM epidemiology and drug susceptibility was performed.
METHODS
Data on the epidemiology of 7,469 NTM clinical isolates identified in Italy in 2016-2020 and on the minimum inhibitory concentrations (MICs) of 1,506 of these strains were analysed.
RESULTS
Overall, 63 species were identified in 42 hospital laboratories located in 16 out of 20 regions, with Mycobacterium avium complex (MAC) being the most frequently isolated, followed by M. gordonae, M. xenopi, M. abscessus. The MICs of 12 drugs for MAC, M. xenopi, M. kansasii, M. abscessus, M. fortuitum and M. chelonae were interpreted for clinical significance (susceptible, intermediate, resistant) based on the guidelines published by the Clinical and Laboratory Standards Institute in November 2018.
CONCLUSIONS
Our data are in line with other nationwide studies and may be of value for further update of microbiological and clinical guidelines.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests; Italy
PubMed: 37337988
DOI: 10.4415/ANN_23_02_06 -
Antimicrobial Agents and Chemotherapy Oct 2023Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an...
Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.
Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).
Topics: Humans; Female; Male; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Cystic Fibrosis; Mycobacterium abscessus; Anti-Bacterial Agents; Outcome Assessment, Health Care
PubMed: 37768312
DOI: 10.1128/aac.00824-23 -
Annals of Clinical Microbiology and... Feb 2023Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important... (Review)
Review
Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is an increasingly recognised global health issue. Studies have suggested that neutrophils may play an important role in controlling NTM infection and contribute to protective immune responses within the early phase of infection. However, these cells are also adversely associated with disease progression and exacerbation and can contribute to pathology, for example in the development of bronchiectasis. In this review, we discuss the key findings and latest evidence regarding the diverse functions of neutrophils in NTM infection. First, we focus on studies that implicate neutrophils in the early response to NTM infection and the evidence reporting neutrophils' capability to kill NTM. Next, we present an overview of the positive and negative effects that characterise the bidirectional relationship between neutrophils and adaptive immunity. We consider the pathological role of neutrophils in driving the clinical phenotype of NTM-PD including bronchiectasis. Finally, we highlight the current promising treatments in development targeting neutrophils in airways diseases. Clearly, more insights on the roles of neutrophils in NTM-PD are needed in order to inform both preventative strategies and host-directed therapy for these important infections.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Neutrophils; Lung Diseases; Bronchiectasis
PubMed: 36800956
DOI: 10.1186/s12941-023-00562-6 -
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 -
Chest May 2022
Topics: Biomarkers; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 35526881
DOI: 10.1016/j.chest.2021.12.646 -
Respiratory Research Dec 2022Non-tuberculous mycobacterial pulmonary disease (NTM-PD) poses a substantial patient, healthcare, and economic burden. Managing NTM-PD remains challenging, and factors... (Review)
Review
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.
Topics: Humans; Nontuberculous Mycobacteria; Lung Diseases; Mycobacterium avium Complex; Anti-Bacterial Agents; Drug Development; Mycobacterium Infections, Nontuberculous
PubMed: 36566170
DOI: 10.1186/s12931-022-02299-w