Employing Multicolor Melting Curve Analysis to Rapidly Identify Non-Tuberculous Mycobacteria in Patients with Bronchiectasis: A Study from a Pulmonary Hospital in the Fuzhou District of China, 2018-2022.

Non-tuberculous mycobacteria (NTM) infection is common in bronchiectasis, with rising incidence globally. However, investigation into NTM in bronchiectasis patients in China remains relatively limited. This work aimed to identify and understand the features of NTM in bronchiectasis patient in Fuzhou district of China. The pulmonary samples were collected from 281 bronchiectasis patients with suspected NTM infection in Fuzhou, 2018-2022. MPB64 antigen detection was employed for the preliminary evaluation of NTM. Further NTM identification was realized using gene chip and gene sequencing. Among 281 patients, 172 (61.21%) patients were NTM-positive (58.72%) according to MPB64 antigen detection, with females (58.72%) outnumbering males (41.28%) and the highest prevalence in the age group of 46-65 years. In total, 47 NTM single infections and 3 mixed infections (1 Mycobacterium tuberculosis complex-M. intracellulare, 1 M. avium-M. intracellulare, and 1 M. abscessus-M. intracellulare) were identified through multicolor melting curve analysis (MMCA), which was compared with gene sequencing results. Both methods suggested Mycobacterium (M.) intracellulare, M. abscessus, and M. avium as the primary NTM species affecting bronchiectasis patients. M. intracellulare and M. abscessus were more frequent in females than males with the highest prevalence in the age group of 46-65 years according to MMCA. This research provides novel insights into the epidemiological and clinical features of NTM in bronchiectasis patients in Southeastern China. Significantly, M. intracellulare, M. abscessus, and M. avium were identified as the major NTM species, contributing to a better understanding and management of bronchiectasis accompanied by NTM infection.

Shower dehumidification to reduce nontuberculous mycobacteria aerosolization.

OBJECTIVE: Nontuberculous mycobacteria (NTM) are environmentally acquired opportunistic pathogens that can cause recalcitrant lung disease. Prior reports have demonstrated links between shower use and infections, yet the aerosolization of NTM from showerheads, as well as the humidity levels that may modulate NTM aerosolization from showerheads is less studied. The objective of the current study was to investigate the role of humidity in NTM aerosolization among showers in homes located in a geographic area with high lung disease incidence, Hawai'i, and test whether deployment of a dehumidifier in well-ventilated bathrooms reduce NTM exposure. RESULTS: Across two sampling events and five showers, existing NTM showerhead biofilms along with shower air were sampled at three points: pre-shower, post-shower, and post-dehumidification. In each of the sampling events, respiratory relevant NTM species were identified from shower biofilms, which were also detected in aerosolized shower air after showering events, but not after the shower was dehumidified and bathrooms vented. While sample size was small, these data suggest running a shower is a possible source of NTM aerosolization and using a commercial household dehumidifier in conjunction with opening bathroom doors and windows may be simple, cost-effective interventions to reduce environmental NTM exposures.

Non-Tuberculous Mycobacterial isolates from Panama: A retrospective 5-year analysis (2017-2021).

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.

Prevalence and Clinical Implications of Nontuberculous Mycobacteria Isolation and Infection among Patients with Bronchiectasis in the Jerusalem Area.

BACKGROUND: Bronchiectasis is an obstructive chronic lung disease characterized by structural changes in large and small airways, namely permanent widening of bronchial lumen resulting in chronic inflammation and infection. Nontuberculous mycobacteria (NTM) are environmental mycobacteria that may cause human infection or colonization with over 150 species identified to date. Bronchiectasis with NTM colonization or infection is often encountered but with varying prevalence and unknown clinical or prognostic significance. OBJECTIVES: To find the prevalence of NTM among patients with bronchiectasis in the Jerusalem district. To assess whether there were clinical differences between patients with bronchiectasis who were isolated with NTM and those without. METHODS: In this retrospective observational research study, we reviewed all computerized medical charts of patients over 18 years of age, who were diagnosed with bronchiectasis at Hadassah Medical Centers in Jerusalem between 2012 and 2017. We assessed the prevalence of NTM pulmonary disease. To compare patients with and without NTM, we reviewed and analyzed clinical, radiological, and microbiological data of all NTM patients and a group of controls in a 4:1 ratio. RESULTS: Prevalence of NTM among bronchiectasis patients was 5.1%, slightly lower than previously reported in Israel. We did not find clinically or radiological significant differences in patients with NTM disease compared to controls. This result included a similar number of exacerbations, hospitalization rates, number of lobes involved, and pulmonary function tests. CONCLUSIONS: Bronchiectasis patients with isolation of Pseudomonas aeruginosa experienced more exacerbations than patients with other isolates, consistent with previous studies.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study.

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

Five-year species distribution and antimicrobial susceptibility of non-tuberculous mycobacteria in Malaysia, 2018-2022.

Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy.

IMPORTANCE: Mycobacterial infection is a major threat to public health worldwide. Accurate identification of infected species and drug resistance detection are critical factors in treatment. We focused on shortening the turn-around time of identifying mycobacteria species and antibiotic resistance tests.

Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

A cluster of three extrapulmonary Mycobacterium abscessus infections linked to well-maintained water-based heater-cooler devices.

BACKGROUND: Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery. METHODS: Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission. RESULTS: Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected. CONCLUSIONS: Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.

Trend of nontuberculous mycobacteria species and minimal inhibitory concentration in a referral laboratory in Korea from 2013 to 2019.

BACKGROUND: This study investigated the trends of nontuberculous mycobacterial (NTM) isolates and the minimal inhibitory concentrations (MIC) of antimicrobial agents in Korea. METHODS: Data from 2013 to 2019 were collected from 69 medical institutions through 12 branches of the Korean Institute of Tuberculosis. NTM identification was conducted using the Advansure Mycobacteria Genoblot assay. The MIC of antibiotics against NTM species were measured using the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: Over seven years, 86,194 NTM identifications were requested, with an annual increase from 8034 in 2013-17,229 in 2019. The most frequently identified NTM species were M. intracellulare (33,467; 47.3%) and M. avium (19,818; 27.2%), followed by M. abscessus (6858; 9.4%) and M. massiliense (3156; 4.3%). Regarding the antimicrobial agents, imipenem exhibited the greatest difference in MIC between M. intracellulare and M. avium, whereas clarithromycin showed the most significant difference between M. abscessus and M. massiliense. No notable changes were observed in the annual MIC distribution of most antibacterial agents, except for clarithromycin in M. abscessus. CONCLUSIONS: The prevalence of NTM in Korea is gradually increasing, and follow-up studies on NTM isolates identified as the causative agents of infection are needed.

Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis.

INTRODUCTION: Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619-623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce. MAIN BODY: This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies. CONCLUSIONS: The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.

Latest status of non-tuberculous mycobacteria prevalence in Türkiye and the world: Systematic review.

Non-tuberculous mycobacteria (NTM) can cause diseases not only in individuals with compromised immune systems but also in those with normal immune function. This study aimed to compare the prevalence of NTM in Türkiye and worldwide between 2012 and 2022. This study was designed following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure. A systematic search was conducted between January 2012 and September 2022 using different electronic databases, including Pubmed, Medline, Embase, Web of Science, Ebsco, Scopus, Türk Medline, and Google Scholar. During the literature review process, titles and abstracts were examined and the full texts of the studies were accessed. In 13 research articles from Türkiye included in the study, a total of 17.293 samples were studied and a total of 1304 NTM (7.54%) strains were isolated from these samples. Among the 1304 NTM strains reported from Türkiye, the top three most frequently isolated species were M. abscessus (29.83%), M. lentiflavum (14.97%), M. fortuitum (14.38%). In 35 studies included from around the world, a total of 512.626 samples were studied and a total of 12.631 NTM (2.46%) strains were isolated from these samples. Among the 12631 NTM strains isolated, the top three most frequently isolated species were M. intracellulare (28.13%), M. avium (17.70%) and M. abscessus (14.88%). This study unveiled the global prevalence of NTM-infected patients, detailing species distribution and microbiological diagnostic methods. Variations in NTM spread were observed, influenced by diverse factors.

A narrative review of nontuberculous mycobacterial pulmonary disease: microbiology, epidemiology, diagnosis, and management challenges.

INTRODUCTION: Nontuberculous mycobacteria (NTM) are a diverse group of mycobacterial species that are ubiquitous in the environment. They are opportunistic pathogens that can cause a range of diseases, especially in individuals with underlying structural lung disease or compromised immune systems. AREAS COVERED: This paper provides an in-depth analysis of NTM infections, including microbiology, environmental sources and transmission pathways, risk factors for disease, epidemiology, clinical manifestations and diagnostic approaches, guideline-based treatment recommendations, drugs under development, and management challenges. EXPERT OPINION: Future approaches to the management of NTM pulmonary disease will require therapies that are well tolerated, can be taken for a shorter time period and perhaps less frequently, have few drug-drug interactions, and are active against the various strains of pathogens. As the numbers of infections increase, such therapies will be welcomed by clinicians and patients.

A case-control study on the risk factors associated with the occurrence of non-tuberculous mycobacteria pulmonary disease in bronchiectasis patients.

OBJECTIVE: The objective of this study is to analyze the risk factors associated with bronchiectasis combined with non-tuberculous mycobacteria pulmonary disease(NTM-PD) and provide a basis for more effective prevention and treatment strategies. METHODS: The study subjects for this manuscript were patients with bronchiectasis who were admitted to the infection department between January 2021 and June 2023.There were 34 patients with NTM-PD in the observation group, and 52 patients with simple bronchiectasis in the control group. Basic information, imaging features, serum albumin levels, and infection indicators were collected from both groups of patients.Univariate and multivariate logistic regression analysis were performed to analyze the risk factors for NTM-PD in patients with bronchiectasis. RESULTS: Multivariate logistic regression analysis revealed that bronchiectasis exacerbation occurring at least twice a year(OR = 3.884, 95% CI: 1.200-12.568), involvement of three or more lung lobes with bronchiectasis (OR = 3.932, 95% CI: 1.208-12.800), hypoalbuminemia (OR = 3.221, 95% CI: 1.015-10.219), and the NLR index (OR = 1.595, 95% CI: 1.200-2.119) were significant risk factors for non-tuberculous mycobacteria pulmonary disease in individuals with bronchiectasis (P < 0.05). CONCLUSION: Patients with bronchiectasis accompanied by NTM-PD present specific risk factors that should be promptly addressed through prevention and treatment.

Epidemiology of Nontuberculous Mycobacteria in Tuberculosis suspects, Southwest of China, 2017-2022.

Objectives: This study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022. Methods: We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. Results: The number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract. Conclusion: The NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.

Alterations in lung and gut microbiota reduce diversity in patients with nontuberculous mycobacterial pulmonary disease.

BACKGROUND/AIMS: Although the incidence of nontuberculous mycobacteria pulmonary disease (NTM-PD), a chronic infectious disease, is increasing, lung and gut microbiota dysbiosis in NTM patients has rarely been studied and was therefore the focus of this study. METHODS: We analyzed the microbiota diversity in sputum and stool samples from 10 healthy subjects and 10 patients with NTM-PD through sequencing of the V3 and V4 regions of the 16S rRNA gene. In NTM-PD patients, we comparatively evaluated the microbiota diversity according to the body mass index (BMI), with BMI ≤ 18.5 kg/m2 defined as "underweight" and BMI > 18.5 kg/m2 as "others." RESULTS: The sputum microbiota from NTM-PD patients tended to have lower index values of amplicon sequence variant richness, Shannon evenness, and beta diversity than those from the control group. Furthermore, NTM-PD patients with a low BMI had a lower microbiota diversity than patients with high BMI. Fecal samples from NTM-PD patients also significantly differed in alpha and beta diversity compared with the control group and exhibited a diversity pattern similar to that found in sputum samples. CONCLUSION: Our results reveal that the lung and gut microbiota of patients with NTM-PD exhibit an altered distribution and reduced richness and diversity.

Environmental Sources and Transmission of Nontuberculous Mycobacteria.

The field of environmental nontuberculous mycobacteria (NTM) is benefiting from a new era of genomics that has catapulted our understanding of preferred niches, transmission, and outbreak investigations. The ability to forecast environmental features that promote or reduce environmental NTM prevalence will greatly improve with coordinated environmental sampling and by elevating the necessity for uniform disease notifications. Studies that synergize environmental biology, isolate notifications, and comparative genomics in prospective, longitudinal studies, particularly during climate changes and weather events, will be useful to solve longstanding NTM public health quandaries.

Global Epidemiology of Nontuberculous Mycobacterial Pulmonary Disease: A Review.

Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium avium. Single-center studies also support increasing trends as well as a persistent burden of undiagnosed NTM among persons suspected of having tuberculosis (TB), in countries with moderate-to-high TB prevalence. Cumulative exposure to water and soil presents an increased risk to susceptible hosts, and trace metals in water supply are recently recognized risk factors. Establishing standard case definitions for subnational and national surveillance systems with mandatory notification of NTM-PD are needed to allow comparisons within and across countries and regions.