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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 -
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 -
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 -
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 -
Infection Jun 2023
Topics: Humans; Abscess; Mycobacterium; Muscles; Nontuberculous Mycobacteria
PubMed: 36472781
DOI: 10.1007/s15010-022-01961-1 -
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