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Microbiology Spectrum Apr 2017Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some... (Review)
Review
Despite the ubiqitous nature of Mycobacterium avium complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient. Successful treatment requires a multipronged approach that includes antibiotics, aggressive pulmonary hygiene, and sometimes resection of the diseased lung. A combination of azithromycin, rifampin, and ethambutol administered three times weekly is recommend for nodular bronchiectatic disease, whereas the same regimen may be used for cavitary disease but administered daily and often with inclusion of a parenteral aminoglycoside. Disseminated MAC (DMAC) is almost exclusively seen in patients with late-stage AIDS and can be treated with a macrolide in combination with ethambutol, with or without rifabutin: the most important intervention in this setting is to gain HIV control with the use of potent antiretroviral therapy. Treatment outcomes for many patients with MAC disease remain suboptimal, so new drugs and treatment regimens are greatly needed. Given the high rate of reinfection after cure, one of the greatest needs is a better understanding of where infection occurs and how this can be prevented.
Topics: Anti-Bacterial Agents; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Treatment Outcome
PubMed: 28429679
DOI: 10.1128/microbiolspec.TNMI7-0045-2017 -
Journal of Korean Medical Science May 2016Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung... (Review)
Review
Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Sputum
PubMed: 27134484
DOI: 10.3346/jkms.2016.31.5.649 -
Clinical Microbiology Reviews Jul 1993Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency... (Review)
Review
Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.
Topics: AIDS-Related Opportunistic Infections; Animals; Humans; Immunity, Cellular; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection
PubMed: 8358707
DOI: 10.1128/CMR.6.3.266 -
The European Respiratory Journal Sep 2017
Topics: Humans; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phenotype
PubMed: 28954776
DOI: 10.1183/13993003.01380-2017 -
Frontiers in Immunology 2020complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and... (Review)
Review
complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
Topics: Anti-Bacterial Agents; Humans; Immunologic Factors; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Precision Medicine
PubMed: 33552087
DOI: 10.3389/fimmu.2020.623119 -
Journal of Global Antimicrobial... Sep 2021The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The incidence of infections due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MABS) is increasing worldwide. Current antimycobacterial agents are not sufficiently effective against nontuberculous mycobacteria (NTM) and there is a need for new drugs. This study aimed to estimate the overall in vitro activity of clofazimine (CFZ) against MAC and MABS clinical isolates.
METHODS
We systematically searched four databases up to 1 March 2020 to identify relevant studies. Studies were included if they used the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). We assessed the pooled in vitro CFZ resistance rate in MAC and MABS clinical isolates using a random- effects model. Sources of heterogeneity were evaluated using Cochran's Q and the I statistic. Potential for publication bias was explored using Begg's and Egger's tests. All analyses were conducted using Stata 14.0.
RESULTS
A total of 20 publications (11 reports for MAC and 15 for MABS) were included. The pooled rates of in vitro resistance to CFZ in clinical isolates of MAC and MABS were 9.0% [95% confidence interval (CI) 3.0-17.0%] and 16.0% (95% CI 4.0-34.0%), respectively. There was no evidence of publication bias.
CONCLUSION
This study reports the frequency of CFZ resistance in clinical isolates of MAC and MABS. According to the results, establishing accurate DST methods for detecting CFZ resistance, performing DST for all NTM isolates to provide effective treatment, and continuous monitoring of drug resistance are suggested for the prevention and control of CFZ-resistant NTM.
Topics: Clofazimine; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis
PubMed: 34153525
DOI: 10.1016/j.jgar.2021.06.002 -
Seminars in Respiratory and Critical... Apr 2015Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two... (Review)
Review
Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines. While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease. Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene. Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to nonmodifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection.
Topics: Anti-Bacterial Agents; Bronchiectasis; Cystic Fibrosis; Humans; Macrolides; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 25826589
DOI: 10.1055/s-0035-1546751 -
International Archives of Allergy and... 2023Cervical scrofulous lymphadenitis due to Mycobacterium avium complex (MAC) in immunocompetent adults is a rare disease. The presence of MAC infections demands meticulous...
INTRODUCTION
Cervical scrofulous lymphadenitis due to Mycobacterium avium complex (MAC) in immunocompetent adults is a rare disease. The presence of MAC infections demands meticulous clinical evaluation of patients along with detailed phenotypic and functional evaluation of their immune system including next-generation sequencing (NGS) analyses of target genes.
METHODS
Exact clinical histories of the index patients both suffering from retromandibular/cervical scrofulous lymphadenitis were obtained along with phenotypic and functional immunological evaluations of leukocyte populations followed by targeted NGS-based sequencing of candidate genes.
RESULTS
Immunological investigations showed normal serum immunoglobulin and complement levels, but lymphopenia, which was caused by significantly reduced CD3+CD4+CD45RO+ memory T-cell and CD19+ B-cell numbers. Despite normal T-cell proliferation to a number of accessory cell-dependent and -independent stimuli, the PBMC of both patients elaborated clearly reduced levels of a number of cytokines, including IFN-γ, IL-10, IL-12p70, IL-1α, IL-1β, and TNF-α upon TCR-dependent T-cell stimulation with CD3-coated beads but also superantigens. The IFN-γ production deficiency was confirmed for CD3+CD4+ helper and CD4+CD8+ cytotoxic T cells on the single-cell level by multiparametric flow cytometry irrespective of whether PMA/ionomycin-stimulated whole blood cells or gradient-purified PBMC was analyzed. In the female patient L1, targeted NGS-based sequencing revealed a homozygous c.110T>C mutation in the interferon-γ receptor type 1 (IFNGR1) leading to significantly reduced receptor expression on both CD14+ monocytes and CD3+ T cells. Patient S2 presented with normal IFNGR1 expression on CD14+ monocytes but significantly reduced IFNGR1 expression on CD3+ T cells, despite the absence of detectable homozygous mutations in the IFNGR1 itself or disease-related target genes. Exogenous addition of increasing doses of IFN-γ resulted in proper upregulation of high-affinity FcγRI (CD64) on monocytes from patient S2, whereas monocytes from patient L1 showed only partial induction of CD64 expression after incubation with high doses of IFN-γ.
CONCLUSION
A detailed phenotypic and functional immunological examination is urgently required to determine the cause of a clinically relevant immunodeficiency, despite detailed genetic analyses.
Topics: Adult; Humans; Female; Mycobacterium avium Complex; Leukocytes, Mononuclear; Mycobacterium avium-intracellulare Infection; Cytokines; Lymphadenitis
PubMed: 37279717
DOI: 10.1159/000530844 -
Journal of Applied Microbiology Aug 2012Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major public health concern. It is responsible for a wide spectrum of disease dependent on... (Review)
Review
Mycobacterium avium complex (MAC) is a group of opportunistic pathogens of major public health concern. It is responsible for a wide spectrum of disease dependent on subspecies, route of infection and patients pre-existing conditions. Presently, there is limited research on the incidence of MAC infection that considers both pulmonary and other clinical manifestations. MAC has been isolated from various terrestrial and aquatic environments including natural waters, engineered water systems and soils. Identifying the specific environmental sources responsible for human infection is essential in minimizing disease prevalence. This paper reviews current literature and case studies regarding the wide spectrum of disease caused by MAC and the role of potable water in disease transmission. Potable water was recognized as a putative pathway for MAC infection. Contaminated potable water sources associated with human infection included warm water distribution systems, showers, faucets, household drinking water, swimming pools and hot tub spas. MAC can maintain long-term contamination of potable water sources through its high resistance to disinfectants, association with biofilms and intracellular parasitism of free-living protozoa. Further research is required to investigate the efficiency of water treatment processes against MAC and into construction and maintenance of warm water distribution systems and the role they play in MAC proliferation.
Topics: Biofilms; Drinking Water; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Water Microbiology; Water Supply
PubMed: 22471411
DOI: 10.1111/j.1365-2672.2012.05298.x -
BioMed Research International 2016The nontuberculous mycobacteria are typically environmental organisms residing in soil and water. These microorganisms can cause a wide range of clinical diseases;... (Review)
Review
The nontuberculous mycobacteria are typically environmental organisms residing in soil and water. These microorganisms can cause a wide range of clinical diseases; pulmonary disease is most frequent, followed by lymphadenitis in children, skin and soft tissue disease, and rare extra pulmonary or disseminated infections. Mycobacterium avium complex is the second most common cause of pulmonary mycobacterioses after M. tuberculosis. This review covers the clinical and laboratory diagnosis of infection caused by the members of this complex and particularities for the treatment of different disease types and patient populations.
Topics: Animals; Disease Reservoirs; Environmental Microbiology; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Risk Factors
PubMed: 27556033
DOI: 10.1155/2016/4387461