Abstract
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.
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
complex,
, and
among the slowly growing NTM and
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.
Abstract
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.
Highlights • Non-tuberculous mycobacteria (NTM) are an emerging cause of pulmonary infection among apparently immunocompetent persons worldwide. • NTM pulmonary disease afflicts persons with ...pre-existing structural pulmonary diseases (e.g. prior tuberculosis, chronic obstructive pulmonary disease, cystic fibrosis), but emerging data suggest that many persons without such diseases are genetically susceptible to pulmonary infection with NTM. • The diagnosis of NTM pulmonary infection relies on a combination of symptoms (which may be subtle), imaging (primarily high-resolution computed tomography), and microbiological findings (increasingly supplemented by molecular testing). • The treatment of NTM pulmonary disease is challenging and should be tailored to the particular patient, based on knowledge of the infecting species and appropriate antimicrobial susceptibility testing.
Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and ...uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures. We identified fundamental macrophage reprogramming events that parallel E-cadherin-dependent mesenchymal-epithelial transitions. Macrophage-specific disruption of E-cadherin function resulted in disordered granuloma formation, enhanced immune cell access, decreased bacterial burden, and increased host survival, suggesting that the granuloma can also serve a bacteria-protective role. Granuloma macrophages in humans with tuberculosis were similarly transformed. Thus, during mycobacterial infection, granuloma macrophages are broadly reprogrammed by epithelial modules, and this reprogramming alters the trajectory of infection and the associated immune response.
Display omitted
•Macrophages mobilize classical epithelial modules during granuloma formation•Macrophage reprogramming shares features of mesenchymal-epithelial transitions•Inhibition of macrophage epithelialization leads to disordered granulomas•Granuloma disruption increases immune access and promotes host survival
A hallmark of tuberculosis is aggregation of macrophages into a structure termed the granuloma. Cronan et al. show that macrophages deploy classical epithelialization pathways to construct mycobacterial granulomas. This reprogramming is host detrimental, as macrophage-specific inhibition of the process enhances host survival and immune cell access and reduces bacterial burden.
Purpose
Invasive
Mycobacterium marinum
disease (tenosynovitis and osteomyelitis) may be an increasingly common manifestation of
M. marinum
infection that presents unique diagnostic and therapeutic ...challenges. We conducted a retrospective case series and literature review of
M. marinum
infection to better understand the clinical spectrum of invasive versus cutaneous disease.
Methods
We reviewed electronic medical records for all
M. marinum
infections at Duke University Medical Center from January 1, 1996 to April 30, 2014. Published case series of
M. marinum
infection since 1990 reporting >5 cases were systematically ascertained and reviewed.
Results
Twenty-eight cases of
M. marinum
infection were identified from our institution. Twenty cases (87 %) involved aquatic exposure, and 26 (93 %) involved finger and/or hand lesions. Median time to diagnosis was 3.5 months. Nineteen (68 %) cases had invasive infection, and 9 (32 %) were cutaneous; invasive infection was more common with older age. Granulomatous inflammation and acid-fast bacilli were noted on pathologic examination in 11 (58 %) and 3 (16 %) cases, respectively. Primarily monotherapy was used in 2 (12 %) cases, dual therapy in 8 (47 %) cases, and three-drug therapy in 7 (41 %) cases; three-drug therapy was more common with invasive infection. Median duration of treatment was 5 months. Adjunctive surgery was performed for 18 (95 %) cases of invasive infection and 4 (44 %) of cutaneous infection. Twenty-one (75 %) cases improved, while 7 (25 %) were lost to follow-up.
Conclusions
Distinguishing between invasive and cutaneous
M. marinum
infection may have important consequences in terms of antibiotic choice and need for adjunctive surgery.
Nontuberculous mycobacteria (NTM) are opportunistically pathogenic bacteria that are found abundantly in the soil and water. Susceptible individuals exposed to NTM-containing aerosols from ...environmental sources may develop NTM pulmonary disease (NTM-PD). Reported survival after NTM-PD diagnosis varies widely among existing studies. Prior work has suggested that mortality among persons with NTM-PD is primarily driven by comorbidities rather than NTM-PD.
We retrospectively identified a cohort of patients in the Duke University Health System who were diagnosed with NTM-PD between 1996 and 2015. Hospitalizations and survival were compared among patients with NTM-PD with and without other comorbidities. Additionally, survival among patients with NTM-PD was compared with standardized mortality data for a similar cohort of the general population.
Patients with NTM-PD without other comorbidities had 0.65 hospitalizations/1000 patient-days compared with 1.37 hospitalizations/1000 patient-days for patients with other comorbidities. Compared with a cohort of the general population, expected survival decreased by approximately 4 years for a diagnosis of NTM-PD without comorbidities and 8.6 years for a diagnosis of NTM-PD with comorbidities. Mortality 5 years after diagnosis was 25.0% and 44.9% among NTM patients without and with comorbidities, respectively, compared with 5.7% in the general-population cohort.
NTM-PD was associated with significant morbidity that was worse in patients with comorbidities. Patients with NTM-PD, even without comorbidities, had worse survival than expected.
Resistance to antimycobacterial drugs is a major barrier to effective treatment of
Mycobacterium tuberculosis
infection. Molecular diagnostic techniques based on the association between specific gene ...mutations and phenotypic resistance to certain drugs offer the opportunity to rapidly ascertain whether drug resistance is present and to alter treatment before further resistance develops. Current barriers to successful implementation of rapid diagnostics include imperfect knowledge regarding the full spectrum of mutations associated with resistance, limited utilization of molecular diagnostics where they are most needed, and the requirement for specialized laboratory facilities to perform molecular testing. Further understanding of genotypic-phenotypic correlates of resistance and streamlined implementation platforms will be necessary to optimize the public health impact of molecular resistance testing for
M. tuberculosis
.
PDF
