-
Mayo Clinic Proceedings Feb 2024
Topics: Humans; Mycobacterium marinum; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis
PubMed: 38309933
DOI: 10.1016/j.mayocp.2023.08.005 -
Clinical Microbiology and Infection :... Jun 2024Mycobacterium abscessus (Mab) is considered as the most pathogenic rapid-growing mycobacteria in humans, causing pulmonary and extra-pulmonary diseases, especially in... (Review)
Review
BACKGROUND
Mycobacterium abscessus (Mab) is considered as the most pathogenic rapid-growing mycobacteria in humans, causing pulmonary and extra-pulmonary diseases, especially in patients with cystic fibrosis. Mab shows intrinsic and acquired resistance to many drugs, leaving limited treatment options that lead to a generally poor prognosis. The standard therapeutic regimen last for more than 6 months and consists of a drug cocktail that ideally includes a macrolide and amikacin. Yet, toxicity and efficacy are suboptimal due also to the high toxicity. There is a need to introduce innovative and out-of-the-box approaches to improve treatments.
OBJECTIVES
In this narrative review, we summarize the recent research on the alternative strategies proposed and discuss the importance of using appropriate experimental assays to assess their activity.
SOURCES
Included articles were identified by searching PubMed and MEDLINE until June 2023. The search terms were 'Mycobacterium abscessus', 'antimicrobial', and 'alternative therapies'. Additional relevant references were obtained from articles retrieved from the primary search.
CONTENT
Therapies against Mab including host directed therapies, repurposed drugs, phage therapy, anti-virulence strategies, essential oils, and inhalation therapies.
IMPLICATIONS
Alternative treatments may represent a valid tool to cope the burden of antimicrobial resistance in Mab-caused diseases.
Topics: Mycobacterium abscessus; Humans; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Complementary Therapies; Drug Repositioning; Phage Therapy
PubMed: 37820951
DOI: 10.1016/j.cmi.2023.10.001 -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacteria (NTM) pulmonary disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The existence of host... (Review)
Review
Nontuberculous mycobacteria (NTM) pulmonary disease is a chronic progressive pulmonary infectious disease caused by low virulence pathogens. The existence of host susceptibility to NTM infection has been recognized from a high incidence among Asians compared to other populations in the United States, a high incidence among slender, middle-aged women, and the presence of familial clusters. Recent whole exome sequencing and genome-wide association studies have identified immune, CFTR, cilia, connective tissue and ion homeostasis genes as host susceptibility genes. Large-scale international collaborative studies and functional analyses are expected to elucidate host susceptibility in the future.
Topics: Middle Aged; Humans; Female; United States; Genome-Wide Association Study; Mycobacterium Infections, Nontuberculous; Lung Diseases; Lung; Nontuberculous Mycobacteria
PubMed: 37890911
DOI: 10.1016/j.ccm.2023.07.002 -
PLoS Pathogens Aug 2023Mycobacterium abscessus (Mabs) drives life-shortening mortality in cystic fibrosis (CF) patients, primarily because of its resistance to chemotherapeutic agents. To...
Mycobacterium abscessus (Mabs) drives life-shortening mortality in cystic fibrosis (CF) patients, primarily because of its resistance to chemotherapeutic agents. To date, our knowledge on the host and bacterial determinants driving Mabs pathology in CF patient lung remains rudimentary. Here, we used human airway organoids (AOs) microinjected with smooth (S) or rough (R-)Mabs to evaluate bacteria fitness, host responses to infection, and new treatment efficacy. We show that S Mabs formed biofilm, and R Mabs formed cord serpentines and displayed a higher virulence. While Mabs infection triggers enhanced oxidative stress, pharmacological activation of antioxidant pathways resulted in better control of Mabs growth and reduced virulence. Genetic and pharmacological inhibition of the CFTR is associated with better growth and higher virulence of S and R Mabs. Finally, pharmacological activation of antioxidant pathways inhibited Mabs growth, at least in part through the quinone oxidoreductase NQO1, and improved efficacy in combination with cefoxitin, a first line antibiotic. In conclusion, we have established AOs as a suitable human system to decipher mechanisms of CF-driven respiratory infection by Mabs and propose boosting of the NRF2-NQO1 axis as a potential host-directed strategy to improve Mabs infection control.
Topics: Humans; Cystic Fibrosis; Mycobacterium abscessus; Antioxidants; Oxidation-Reduction; Oxidative Stress
PubMed: 37619220
DOI: 10.1371/journal.ppat.1011559 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic... (Review)
Review
Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic evaluation follows the established criteria for all nontuberculous mycobacteria, but with certain qualifications given species-specific and regional differences in pathogenicity. Clinicians should first institute nonpharmacologic management and evaluate clinical, radiologic, and microbiologic factors in the decision regarding antimycobacterial therapy. Treatment is challenging, and evidence-based recommendations are limited for most species. Drug susceptibility testing is used to help with regimen selection; however, this approach is imperfect given the uncertain correlation between in vitro activity and clinical response for most drugs.
Topics: Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Lung Diseases
PubMed: 37890917
DOI: 10.1016/j.ccm.2023.06.011 -
Clinical and Experimental Pharmacology... Jul 2023Non-tuberculous mycobacterial infections are gradually increasing worldwide, with slow-growing mycobacteria such as Mycobacterium avium, Mycobacterium intracellulare and...
Non-tuberculous mycobacterial infections are gradually increasing worldwide, with slow-growing mycobacteria such as Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium kansasii accounting for the majority of cases. The use of tetracyclines has received renewed attention in recent years, and this study was designed to investigate the antibacterial activity of omadacycline, eravacycline, tigecycline, sarecycline, minocycline and doxycycline against M. avium, M. intracellulare and M. kansasii. Susceptibility testing of six tetracyclines was conducted against M. avium, M. intracellulare and M. kansasii isolates, and all the clinical isolates were collected from January 2012 to December 2018. All six agents exhibited poor antibacterial activity against slowly growing mycobacteria (SGM) isolates of three subspecies with MIC and MIC ≥8 μg/mL. M. intracellulare and M. kansasii had lower resistance rates to omadacycline than the other five drugs. The severe resistance of SGM to tetracycline suggests that developing tetracycline-class antibiotics needs to overcome existing resistance mechanisms.
Topics: Nontuberculous Mycobacteria; Tetracycline; Anti-Bacterial Agents; Minocycline
PubMed: 37086075
DOI: 10.1111/1440-1681.13777 -
Radiologia 2023To describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment.
OBJECTIVE
To describe the epidemiology and CT findings for nontuberculous mycobacterial lung infections and outcomes depending on the treatment.
MATERIAL AND METHODS
We retrospectively studied 131 consecutive patients with positive cultures for nontuberculous mycobacteria between 2005 and 2016. We selected those who met the criteria for nontuberculous mycobacterial lung infection. We analysed the epidemiologic data; clinical, microbiological, and radiological findings; treatment; and outcome according to treatment.
RESULTS
We included 34 patients (mean age, 55 y; 67.6% men); 50% were immunodepressed (58.8% of these were HIV+), 20.6% had COPD, 5.9% had known tumors, 5.9% had cystic fibrosis, and 29.4% had no comorbidities. We found that 20.6% had a history of tuberculosis and 20.6% were also infected with other microorganisms. Mycobacterium avium complex was the most frequently isolated germ (52.9%); 7 (20.6%) were also infected with other organisms. The most common CT findings were nodules (64.7%), tree-in-bud pattern (61.8%), centrilobular nodules (44.1 %), consolidations (41.2%), bronchiectasis (35.3%), and cavities (32.4%). We compared findings between men and women and between immunodepressed and immunocompetent patients. Treatment was antituberculosis drugs in 67.6% of patients (72% of whom showed improvement) and conventional antibiotics in 20.6% (all of whom showed radiologic improvement).
CONCLUSION
The diagnosis of nontuberculous mycobacterial lung infections is complex. The clinical and radiologic findings are nonspecific and a significant percentage of pateints can have other, concomitant infections.
Topics: Male; Humans; Female; Middle Aged; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Cystic Fibrosis; Pneumonia; Antitubercular Agents; Lung
PubMed: 37758330
DOI: 10.1016/j.rxeng.2023.09.001 -
International Journal of Molecular... Jul 2023, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with...
, a species of nontuberculous mycobacteria (NTM), is an opportunistic pathogen that is readily cleared by healthy lungs but can cause pulmonary infections in people with chronic airway diseases. Although knowledge pertaining to molecular mechanisms of host defense against NTM is increasing, macrophage receptors that recognize remain poorly defined. Dectin-1, a C-type lectin receptor identified as a fungal receptor, has been shown to be a pathogen recognition receptor (PRR) for both and NTM. To better understand the role of Dectin-1 in host defense against , we tested whether blocking Dectin-1 impaired the uptake of by human macrophages, and we compared pulmonary infection in Dectin-1-deficient and wild-type mice. Blocking antibody for Dectin-1 did not reduce macrophage phagocytosis of , but did reduce the ingestion of the fungal antigen zymosan. Laminarin, a glucan that blocks Dectin-1 and other PRRs, caused decreased phagocytosis of both and zymosan. Dectin-1-/- mice exhibited no defects in the control of infection, and no differences were detected in immune cell populations between wild type and Dectin-1-/- mice. These data demonstrate that murine defense against pulmonary infection, as well as ingestion of by human macrophages, can occur independent of Dectin-1. Thus, additional PRR(s) recognized by laminarin participate in macrophage phagocytosis of
Topics: Humans; Animals; Mice; Mycobacterium abscessus; Zymosan; Macrophages; Phagocytosis; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous
PubMed: 37446240
DOI: 10.3390/ijms241311062 -
Clinical Microbiology and Infection :... Jun 2024Mycobacterium abscessus (MAB) is the mycobacterial species least susceptible to antimicrobials. Infections are difficult to treat, and cure rates are below 50% even... (Review)
Review
BACKGROUND
Mycobacterium abscessus (MAB) is the mycobacterial species least susceptible to antimicrobials. Infections are difficult to treat, and cure rates are below 50% even after a combination of 4-5 drugs for many months.
OBJECTIVES
To examine antimicrobial susceptibilities and treatment recommendations in light of what is known about mechanisms of resistance and pharmacodynamics/pharmacokinetics (PK/PD) interactions.
SOURCES
Original papers on the topics of 'antimicrobials', 'susceptibility', 'treatment', and 'outcome' from 2019 onwards, in the context of the evidence brought by the guidelines published in 2020 for pulmonary infections.
CONTENT
MAB is susceptible in vitro to only a few antimicrobials. Breakpoints were set by the Clinical and Laboratory Standards Institute and are revised by the European Committee on Antimicrobial Susceptibility Testing for epidemiological cut-off values. Innate resistance is due to multiple resistance mechanisms involving efflux pumps, inactivating enzymes, and low drug-target affinity. In addition, MAB may display acquired resistance to macrolides and amikacin through mutations in drug binding sites. Treatment outcomes are better for macrolide-based combinations and MAB subspecies massiliense. New compounds in the family of cyclines, oxazolidinones, and penem-β-lactamase inhibitor combinations (described in another paper), as well as bedaquiline, a new antituberculous agent, are promising, but their efficacy remains to be proven. PK/PD studies, which are critical for establishing optimal dosing regimens, were mainly done for monotherapy and healthy individuals.
IMPLICATIONS
Medical evidence is poor, and randomized clinical trials or standardized cohorts are needed to compare outcomes of patients with similar underlying disease, clinical characteristics, and identified MAB subspecies/sequevar. Microbiological diagnosis and susceptibility testing need to be harmonized to enable the comparison of agents and the testing of new compounds. Testing antimicrobial combinations requires new methods, especially for PK/PD parameters. Molecular testing may help in assessing MAB resistance prior to treatment. New antimicrobials need to be systematically tested against MAB to find an effective antimicrobial regimen.
Topics: Mycobacterium abscessus; Humans; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests; Anti-Bacterial Agents; Drug Resistance, Bacterial; Respiratory Tract Infections
PubMed: 37797824
DOI: 10.1016/j.cmi.2023.09.019