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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 -
Journal of Infection in Developing... Jul 2023Although non-tuberculous mycobacterium (NTM) infection accounts for only a small proportion of fever of unknown origin (FUO) cases, it has become a more common etiology... (Review)
Review
INTRODUCTION
Although non-tuberculous mycobacterium (NTM) infection accounts for only a small proportion of fever of unknown origin (FUO) cases, it has become a more common etiology in recent years. Therefore, we reviewed FUO patients with underlying NTM infection to better understand its clinical features.
METHODOLOGY
The medical records of patients presenting with FUO and diagnosed with NTM infection admitted to Peking Union Medical College Hospital between January 2016 and June 2021 were reviewed. The clinical information of patients whose follow-up data were available were summarized. Specimens submitted for pathogenic identification were processed by mycobacterial culture, acid-fast staining, and mycobacterial nucleic acid detection. IBM SPSS Statistics v22.0 (SPSS, Inc., Chicago, IL, USA) was used for data analysis.
RESULTS
Fifty-five FUO patients were diagnosed with NTM infection (55/785; 7.0% of FUO cases). Patients were mostly middle-aged men and had a relatively long disease course. Seven, 29, and 54 patients had previously no respondence to glucocorticoids, immunosuppressants, and multiple antibiotics, respectively; their inflammatory indexes were significantly increased; and there was no obvious risk of immunosuppression in this group, who were likely to be T.SPOT-TB negative (33/41; 80.5%). The most commonly identified NTM was Mycobacterium intracellulare followed by Mycobacterium chelonae/abscessus, Mycobacterium kansasii, and Mycobacterium avium.
CONCLUSIONS
Microbiological investigations including culture, acid-fast staining, NTM nucleic acid examination, and next-generation sequencing were performed to confirm the diagnosis of NTM in FUO patients. FUO patients should screen for NTM infections so that this important etiology can be recognized, targeted treatments administered early, and outcomes improved.
Topics: Male; Middle Aged; Humans; Mycobacterium Infections, Nontuberculous; Fever of Unknown Origin; Mycobacterium avium Complex; Mycobacterium; Tuberculosis; Nontuberculous Mycobacteria; Retrospective Studies
PubMed: 37515806
DOI: 10.3855/jidc.17610 -
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 -
Antimicrobial Agents and Chemotherapy Sep 2021Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. We recently reported that the antitubercular 4-halogenated benzoxaboroles are active against...
Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. We recently reported that the antitubercular 4-halogenated benzoxaboroles are active against Mycobacterium abscessus. Here, we find that the nonhalogenated benzoxaborole epetraborole, a clinical candidate developed for Gram-negative infections, is also active against M. abscessus and in a mouse model of infection. This expands the repertoire of advanced lead compounds for the discovery of a benzoxaborole-based candidate to treat M. abscessus lung disease.
Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Lung Diseases; Mice; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Nontuberculous Mycobacteria
PubMed: 34280020
DOI: 10.1128/AAC.01156-21 -
Medical Principles and Practice :... 2022Immunocompromised patients are a high-risk group for developing mycobacterial infections with either pulmonary and/or extrapulmonary diseases. Low-cost/density...
BACKGROUND AND OBJECTIVES
Immunocompromised patients are a high-risk group for developing mycobacterial infections with either pulmonary and/or extrapulmonary diseases. Low-cost/density DNA-microarray is considered an easy and efficient method for the detection of typical and atypical mycobacterial species.
MATERIALS AND METHODS
Thirty immunocompromised patients were recruited to provide their clinical specimens (sputum, serum, urine, and lymph node aspirates). Real-time polymerase chain reaction (PCR) and DNA-microarray techniques were performed and compared to the conventional methods of Ziehl-Neelsen staining and Lowenstein Jensen culturing.
RESULTS
Mycobacterium tuberculosis complex was detected in all 30 clinical specimens (100% sensitivity) by real-time PCR and DNA-microarray. Additionally, coinfection with 4 atypical species belonging to nontuberculous mycobacteria was identified in 7 sputum specimens. These atypical mycobacterial species were identified as M. kansasii 10% (n = 3), M. avium complex 6.6% (n = 2), M. gordanae 3.3% (n = 1), and M. peregrinum 3.3% (n = 1).
CONCLUSION
This study documents the presence of certain species of atypical mycobacteria among immunocompromised patients in Egypt.
Topics: DNA; Egypt; Humans; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Sputum; Tuberculosis
PubMed: 35413718
DOI: 10.1159/000524209 -
Emerging Infectious Diseases Jul 2023We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13...
We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.
Topics: Humans; Nontuberculous Mycobacteria; Ontario; Mycobacterium Infections, Nontuberculous; Lung; Lung Diseases
PubMed: 37347810
DOI: 10.3201/eid2907.230216 -
International Journal of... Jun 2015Pulmonary infections with nontuberculous mycobacteria (NTM) are recognized as a problem in immunodeficient individuals and are increasingly common in older people with... (Review)
Review
Pulmonary infections with nontuberculous mycobacteria (NTM) are recognized as a problem in immunodeficient individuals and are increasingly common in older people with no known immune defects. NTM are found in soil and water, but factors influencing transmission from the environment to humans are mostly unknown. Studies of the epidemiology of NTM disease have matched some clinical isolates of NTM with isolates from the patient's local environment. Definitive matching requires strain level differentiation based on molecular analyses, including partial sequencing, PCR-restriction fragment length polymorphism (RFLP) analysis, random amplified polymorphic DNA (RAPD) PCR, repetitive element (rep-) PCR and pulsed field gel electrophoresis (PFGE) of large restriction fragments. These approaches have identified hospital and residential showers and faucets, hot-tubs and garden soil as sources of transmissible pathogenic NTM. However, gaps exist in the literature, with many clinical isolates remaining unidentified within environments that have been tested, and few studies investigating NTM transmission in developing countries. To understand the environmental reservoirs and transmission routes of pathogenic NTM, different environments, countries and climates must be investigated.
Topics: Environmental Microbiology; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 26972876
DOI: 10.1016/j.ijmyco.2015.03.002 -
Journal of Korean Medical Science Aug 2017
Topics: Diagnostic Tests, Routine; Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Republic of Korea; Tertiary Care Centers
PubMed: 28665053
DOI: 10.3346/jkms.2017.32.8.1215 -
Journal of the Formosan Medical... Jun 2020Great progress has recently been made in methodologies for identifying nontuberculous mycobacteria (NTM). Recommendations for drug susceptibility testing (DST) of NTM... (Review)
Review
Great progress has recently been made in methodologies for identifying nontuberculous mycobacteria (NTM). Recommendations for drug susceptibility testing (DST) of NTM have been expanded and updated by the Clinical and Laboratory Standards Institute and are crucial in the management of NTM infections. This article summarizes the clinically relevant molecular methods used to discriminate NTM species and updates the information on DST. Furthermore, recent progress on new antimicrobials against NTM infections is reviewed.
Topics: Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 32423573
DOI: 10.1016/j.jfma.2020.05.002 -
International Journal of Molecular... Jun 2020The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of... (Review)
Review
The incidence and prevalence of non-tuberculous mycobacteria (NTM) infections are steadily increasing worldwide, partially due to the increased incidence of immunocompromised conditions, such as the post-transplantation state. The importance of proper diagnosis and management of NTM infection has been recently recognized. Host immunological responses play integral roles in vulnerability to NTM infections, and may contribute to the onset of specific types of NTM infection. Furthermore, distinct NTM species are known to affect and attenuate these host immune responses in unique manners. Therefore, host immune responses must be understood with respect to each causative NTM species. Here, we review innate, cellular-mediated, and humoral immunity to NTM and provide perspectives on novel diagnostic approaches regarding each NTM species.
Topics: Humans; Immunity; Incidence; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Prevalence
PubMed: 32570978
DOI: 10.3390/ijms21124351