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Clinical Infectious Diseases : An... Aug 2020Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and...
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
Topics: Adult; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium kansasii; Nontuberculous Mycobacteria
PubMed: 32628747
DOI: 10.1093/cid/ciaa241 -
Clinical Microbiology Reviews Jan 2018Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our... (Review)
Review
Humans encounter mycobacterial species due to their ubiquity in different environmental niches. In many individuals, pathogenic mycobacterial species may breach our first-line barrier defenses of the innate immune system and modulate the activation of phagocytes to cause disease of the respiratory tract or the skin and soft tissues, sometimes resulting in disseminated infection. Cutaneous mycobacterial infections may cause a wide range of clinical manifestations, which are divided into four main disease categories: (i) cutaneous manifestations of infection, (ii) Buruli ulcer caused by and other related slowly growing mycobacteria, (iii) leprosy caused by and , and (iv) cutaneous infections caused by rapidly growing mycobacteria. Clinically, cutaneous mycobacterial infections present with widely different clinical presentations, including cellulitis, nonhealing ulcers, subacute or chronic nodular lesions, abscesses, superficial lymphadenitis, verrucous lesions, and other types of findings. Mycobacterial infections of the skin and subcutaneous tissue are associated with important stigma, deformity, and disability. Geography-based environmental exposures influence the epidemiology of cutaneous mycobacterial infections. Cutaneous tuberculosis exhibits different clinical phenotypes acquired through different routes, including via extrinsic inoculation of the tuberculous bacilli and dissemination to the skin from other sites, or represents hypersensitivity reactions to infection. In many settings, leprosy remains an important cause of neurological impairment, deformity, limb loss, and stigma. , a mycobacterial species related to , is linked to diffuse lepromatous leprosy of Lucio and Latapí. produces a mycolactone toxin that leads to subcutaneous tissue destruction and immunosuppression, resulting in deep ulcerations that often produce substantial disfigurement and disability. , a close relative of , is an important cause of cutaneous sporotrichoid nodular lymphangitic lesions. Among patients with advanced immunosuppression, , the complex, and may cause cutaneous or disseminated disease. Rapidly growing mycobacteria, including the group, , and , are increasingly recognized pathogens in cutaneous infections associated particularly with plastic surgery and cosmetic procedures. Skin biopsies of cutaneous lesions to identify acid-fast staining bacilli and cultures represent the cornerstone of diagnosis. Additionally, histopathological evaluation of skin biopsy specimens may be useful in identifying leprosy, Buruli ulcer, and cutaneous tuberculosis. Molecular assays are useful in some cases. The treatment for cutaneous mycobacterial infections depends on the specific pathogen and therefore requires a careful consideration of antimicrobial choices based on official treatment guidelines.
Topics: Animals; Dermatitis; Humans; Mycobacterium; Mycobacterium Infections
PubMed: 30429139
DOI: 10.1128/CMR.00069-18 -
The Indian Journal of Medical Research Sep 2020Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent... (Review)
Review
Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.
Topics: Diagnostic Tests, Routine; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria
PubMed: 33107481
DOI: 10.4103/ijmr.IJMR_902_20 -
Journal of Biomedical Science Jun 2020Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis... (Review)
Review
Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drug-sensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first- and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely successful. In general, the treatment duration is much longer for NTM diseases, compared to TB, and resection surgery of affected organ(s) is part of treatment for patients with NTM diseases that do not respond to the antibiotics treatment. Here, we discuss the epidemiology, diagnosis, and treatment modalities available for TB and NTM diseases of humans.
Topics: Female; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Tuberculosis
PubMed: 32552732
DOI: 10.1186/s12929-020-00667-6 -
International Journal of Infectious... Dec 2022To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. (Review)
Review
OBJECTIVES
To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.
METHODS
A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.
RESULTS
Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).
CONCLUSION
Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium abscessus; Lung Diseases; Pneumonia
PubMed: 36244600
DOI: 10.1016/j.ijid.2022.10.013 -
Microbiology Spectrum Aug 2016The immunocompromised host is at increased risk of Mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. Although Mycobacterium tuberculosis...
The immunocompromised host is at increased risk of Mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. Although Mycobacterium tuberculosis complex is a significant mycobacterial pathogen, nontuberculous mycobacteria causes substantial disease in those with suppressed immune responses. Mycobacterial infections can cause significant morbidity and mortality in this patient population, and rapid identification and susceptibility testing of the mycobacterial species is paramount to patient management and outcomes. Mycobacterial diagnostics has undergone some significant advances in the last two decades with immunodiagnostics (interferon gamma release assay), microscopy (light-emitting diode), culture (automated broth-based systems), identification (direct PCR, sequencing and matrix-assisted laser-desorption ionization-time of flight mass spectrometry) and susceptibility testing (molecular detection of drug resistance from direct specimens or positive cultures). Employing the most rapid and sensitive methods in the mycobacterial laboratory will have a tremendous impact on patient care and, in the case of Mycobacterium tuberculosis complex, in the control of tuberculosis.
Topics: Bacteriological Techniques; Diagnostic Tests, Routine; Disease Susceptibility; Humans; Immunocompromised Host; Mycobacterium Infections
PubMed: 27726808
DOI: 10.1128/microbiolspec.DMIH2-0016-2015 -
Microbiology Spectrum Jan 2017The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of... (Review)
Review
The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. In contrast to other common nontuberculous mycobacteria, M. kansasii is infrequently isolated from natural water sources or soil. The major reservoir appears to be tap water. Infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. Human-to-human transmission is thought not to occur. Clinical syndromes and radiological findings of M. kansasii infection are mostly indistinguishable from that of Mycobacterium tuberculosis, thus requiring microbiological confirmation. Disseminated disease is uncommon in HIV-negative patients and usually associated with severe immunosuppression. The majority of patients with M. kansasii pulmonary disease have underlying pulmonary comorbidities, such as smoking, chronic obstructive pulmonary disease, bronchiectasis, and prior or concurrent M. tuberculosis infection. Surveys in Great Britain, however, noted higher rates, with 8 to 9% of M. kansasii infections presenting with extrapulmonary disease. Common sites of extrapulmonary disease include the lymph nodes, skin, and musculoskeletal and genitourinary systems. The specificity of gamma interferon release assays (IGRAs) for M. tuberculosis may be reduced by M. kansasii infection, as M. kansasii encodes CFP-10 and ESAT-6, two antigens targeted by IGRAs. A study conducted to evaluate the therapy in rifampin-resistant disease found that patients with acquired rifampin resistance were treated with daily high-dose ethambutol, isoniazid, sulfamethoxazole, and pyridoxine combined with aminoglycoside therapy. Given the potential toxicities, particularly with aminoglycoside therapy, clarithromycin and/or moxifloxacin therapy could be considered as alternatives.
Topics: Antitubercular Agents; Environmental Exposure; Global Health; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Water Microbiology
PubMed: 28185617
DOI: 10.1128/microbiolspec.TNMI7-0011-2016 -
Current Opinion in Infectious Diseases Apr 2022The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021. (Review)
Review
PURPOSE OF REVIEW
The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021.
RECENT FINDINGS
Mycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned.
SUMMARY
Mycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.
Topics: Animals; Buruli Ulcer; Drug Therapy, Combination; Humans; Leprostatic Agents; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
PubMed: 35067521
DOI: 10.1097/QCO.0000000000000820 -
International Journal of Molecular... Jan 2022Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of... (Review)
Review
Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection.
Topics: Adaptive Immunity; Animals; Cytokines; Humans; Immunity, Innate; Mutation; Mycobacterium Infections; Receptors, Cytokine; Signal Transduction
PubMed: 35163035
DOI: 10.3390/ijms23031112 -
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