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Journal of Clinical Medicine Aug 2020Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have... (Review)
Review
Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including and . The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of infection. , a slow-growing mycobacterium, is associated with complex (MAC) infections that can cause chronic pulmonary disease, disseminated disease, as well as lymphadenitis. infections are considered one of the most antibiotic-resistant mycobacteria and are associated with pulmonary disease, especially cystic fibrosis, as well as contaminated traumatic skin wounds, postsurgical soft tissue infections, and healthcare-associated infections (HAI). Clinical manifestations of diseases depend on the interaction of the host's immune response and the specific mycobacterial species. This review will give a general overview of the general characteristics, vulnerable populations most at risk, pathogenesis, treatment, and prevention for infections caused by , in the context of MAC, and
PubMed: 32781595
DOI: 10.3390/jcm9082541 -
European Respiratory Review : An... Mar 2022Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently... (Review)
Review
Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently associated with adverse effects and has variable success. In this review, we consider the factors influencing clinicians when treating NTM-PD and discuss outcomes from key studies on the pharmacological management of complex pulmonary disease and pulmonary disease. We highlight issues relating to treatment-related toxicity and provide an overview of repurposed and emerging therapies for NTM-PD.
Topics: Humans; Lung; Lung Diseases; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection
PubMed: 35140106
DOI: 10.1183/16000617.0212-2021 -
The Journal of Infectious Diseases Aug 2020Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of...
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria-which include clinical, radiological, and microbiologic criteria-should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens.
Topics: Administration, Inhalation; Administration, Oral; Aged; Anti-Bacterial Agents; Biomarkers; Bronchoscopy; Disease Progression; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lung; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Professional Practice Gaps; Sputum; Time Factors; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32814943
DOI: 10.1093/infdis/jiaa354 -
Clinical Microbiology and Infection :... Jun 2023For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions of wild-type isolates have not been systematically evaluated despite their...
Towards clinical breakpoints for non-tuberculous mycobacteria - Determination of epidemiological cut off values for the Mycobacterium avium complex and Mycobacterium abscessus using broth microdilution.
OBJECTIVE
For non-tuberculous mycobacteria (NTM), minimum inhibitory concentration (MIC) distributions of wild-type isolates have not been systematically evaluated despite their importance for establishing antimicrobial susceptibility testing (AST) breakpoints.
METHODS
We gathered MIC distributions for drugs used against the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) obtained by commercial broth microdilution (SLOMYCOI and RAPMYCOI) from 12 laboratories. Epidemiological cut-off values (ECOFFs) and tentative ECOFFs (TECOFFs) were determined by EUCAST methodology including quality control (QC) strains.
RESULTS
The clarithromycin ECOFF was 16 mg/L for M. avium (n = 1271) whereas TECOFFs were 8 mg/L for M. intracellulare (n = 415) and 1 mg/L for MAB (n = 1014) confirmed by analysing MAB subspecies without inducible macrolide resistance (n = 235). For amikacin, the ECOFFs were 64 mg/L for MAC and MAB. For moxifloxacin, the WT spanned >8 mg/L for both MAC and MAB. For linezolid, the ECOFF and TECOFF were 64 mg/L for M. avium and M. intracellulare, respectively. Current CLSI breakpoints for amikacin (16 mg/L), moxifloxacin (1 mg/L) and linezolid (8 mg/L) divided the corresponding WT distributions. For QC M. avium and M. peregrinum, ≥95% of MIC values were well within recommended QC ranges.
CONCLUSION
As a first step towards clinical breakpoints for NTM, (T)ECOFFs were defined for several antimicrobials against MAC and MAB. Broad wild-type MIC distributions indicate a need for further method refinement which is now under development within the EUCAST subcommittee for anti-mycobacterial drug susceptibility testing. In addition, we showed that several CLSI NTM breakpoints are not consistent in relation to the (T)ECOFFs.
Topics: Humans; Mycobacterium avium Complex; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Amikacin; Mycobacterium abscessus; Moxifloxacin; Linezolid; Mycobacterium avium-intracellulare Infection; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Macrolides; Mycobacterium tuberculosis; Mycobacterium Infections, Nontuberculous; Mycobacterium avium
PubMed: 36813087
DOI: 10.1016/j.cmi.2023.02.007 -
BMJ Case Reports Mar 2022SummaryHabitual cough suppression leading to non-tuberculous mycobacteria infections and bronchiectasis has been reported. We present a case of a 55-year-old woman with...
SummaryHabitual cough suppression leading to non-tuberculous mycobacteria infections and bronchiectasis has been reported. We present a case of a 55-year-old woman with a chronic history of cough with mild expectoration and frequent lower respiratory tract infections, remitting with antibiotic therapy and other supportive measures. She also reported habitual cough suppression for several years. She was eventually diagnosed with Mycobacterium avium complex (MAC) positive right middle lobe bronchiectasis-Lady Windermere syndrome and obstructive sleep apnoea (OSA), causing disabling symptoms limiting her daily activities. We aim to highlight two key issues-diagnosing MAC infections in a tuberculosis endemic country, and OSA and its long-term clinical implications.
Topics: Bronchiectasis; Cough; Female; Humans; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Nontuberculous Mycobacteria
PubMed: 35256362
DOI: 10.1136/bcr-2021-246285 -
IDCases 2023Synchronous opportunistic infections are luckily rare in people living with HIV (PLWH) in the era of highly effective antiretroviral medications. We describe the case of...
Synchronous opportunistic infections are luckily rare in people living with HIV (PLWH) in the era of highly effective antiretroviral medications. We describe the case of a middle-aged man who presented with diarrhea and shortness of breath and was found to have pneumocystis pneumonia, disseminated histoplasmosis and disseminated mycobacterium avium complex infection along with a new diagnosis of human immunodeficiency virus (HIV) infection. This case highlights that individuals who remain undiagnosed with HIV infection for a long time can still present with concurrent infections and clinicians should remain aware of this.
PubMed: 37207173
DOI: 10.1016/j.idcr.2023.e01786 -
Tuberculosis (Edinburgh, Scotland) Jan 2023Prophylactic efficacy of two different delivery platforms for vaccination against Mycobacterium avium (M. avium) were tested in this study; a subunit and an RNA-based...
Prophylactic efficacy of two different delivery platforms for vaccination against Mycobacterium avium (M. avium) were tested in this study; a subunit and an RNA-based vaccine. The vaccine antigen, ID91, includes four mycobacterial antigens: Rv3619, Rv2389, Rv3478, and Rv1886. We have shown that ID91+GLA-SE is effective against a clinical NTM isolate, M. avium 2-151 smt. Here, we extend these results and show that a heterologous prime/boost strategy with a repRNA-ID91 (replicon RNA) followed by protein ID91+GLA-SE boost is superior to the subunit protein vaccine given as a homologous prime/boost regimen. The repRNA-ID91/ID91+GLA-SE heterologous regimen elicited a higher polyfunctional CD4 T1 immune response when compared to the homologous protein prime/boost regimen. More significantly, among all the vaccine regimens tested only repRNA-ID91/ID91+GLA-SE induced IFN-γ and TNF-secreting CD8 T cells. Furthermore, the repRNA-ID91/ID91+GLA-SE vaccine strategy elicited high systemic proinflammatory cytokine responses and induced strong ID91 and an Ag85B-specific humoral antibody response a pre- and post-challenge with M. avium 2-151 smt. Finally, while all prophylactic prime/boost vaccine regimens elicited a degree of protection in beige mice, the heterologous repRNA-ID91/ID91+GLA-SE vaccine regimen provided greater pulmonary protection than the homologous protein prime/boost regimen. These data indicate that a prophylactic heterologous repRNA-ID91/ID91+GLA-SE vaccine regimen augments immunogenicity and confers protection against M. avium.
Topics: Animals; Mice; CD8-Positive T-Lymphocytes; Mycobacterium avium; Mycobacterium tuberculosis; Vaccination; Cytokines; Vaccines, DNA; Immunization, Secondary
PubMed: 36586154
DOI: 10.1016/j.tube.2022.102302 -
Annals of Agricultural and... Mar 2022The complex (MAC) is a group of acid-resistant bacteria within the Mycobacteriaceae. Their cell walls have a specific structure impervious to many disinfectants.... (Review)
Review
INTRODUCTION AND OBJECTIVE
The complex (MAC) is a group of acid-resistant bacteria within the Mycobacteriaceae. Their cell walls have a specific structure impervious to many disinfectants. Mycobacteria are widespread in the environment and can also be found in food. This aim of the article is to review the current state of knowledge about the sources of infection, symptoms and treatment of MAC diseases in humans and animals, and summarizes the available methods for identifying the bacteria. It pays a special attention to the zoonotic potential of MAC bacteria and possible routes of transmission between humans and animals, including possible food-borne routes.
BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE.
MAC bacterial infections occur both in immunocompetent people and those with functional predispositions and compromised immunity, particularly during HIV infection or immunosuppressive treatment. The incidence of MAC infections in humans is growing, with the most common form of infection being pulmonary disease (MTC-PD); however, there are conflicting reports on the role of paratuberculosis (MAP) in the development of Crohn's disease. MAC bacteria can also attack livestock, household pets, and wild animals. Unfortunately, treatment is lengthy and often fails due to microbiological relapse; there is also increasing evidence of MAC bacteria are developing multi-drug resistance.
CONCLUSIONS
Although new antibiotics are being created to inhibit the growth and division of , there is clearly a need for further research into the virulence factors associated with MAC bacteria. Further studies should also examine the role of MAP in the etiopathogenesis of Crohn's disease.
Topics: Animals; Crohn Disease; HIV Infections; Humans; Mycobacterium avium Complex; Mycobacterium avium subsp. paratuberculosis; Mycobacterium avium-intracellulare Infection
PubMed: 35352901
DOI: 10.26444/aaem/136398