Pulmonary Nontuberculous Mycobacteria Research Articles

Non-tuberculous mycobacterial bone and joint infections - a case series from a tertiary referral centre in Australia.

Non-tuberculous mycobacteria (NTM) are rare causes of bone and joint infection (BJI) and there is limited evidence on which to base management decisions. This study describes 1 year of experience from a multi-disciplinary BJI team which collects data on all cases reviewed at a tertiary referral centre in Queensland, Australia. The database was interrogated for all cases in which NTM were recovered from operative samples. Individual chart review was performed to collect the details of each case. A total of seven cases were managed between 1st February 2021 and 28th February 2022, comprising one patient with chronic osteomyelitis, three with fracture-related infections, two with prosthetic joint infections, and one with infection of a synthetic ligament graft. In contrast to pulmonary NTM infections, most patients were clinically well and immunocompetent, and most infections were propagated by direct inoculation. Time to diagnosis was unknown in three patients, with 1, 2, 2, and 5 months for the remaining four. Rapid growing NTM were diagnosed on routine cultures and specific mycobacterial cultures were confirmatory. Management was characterized by multiple stage surgical procedures and prolonged antimicrobial regimens. Antimicrobial complications were common; however, all patients were infection free at their latest follow up. Despite the inherent limitations, these results suggest that routinely ordering mycobacterial culture is of low yield. There is potential for shorter-term oral antimicrobial treatments. Prospective research is required to optimize treatment regimens and durations.

Assays for Assessing Mycobacterium avium Immunity and Evaluating the Effects of Therapeutics.

In Europe and North America, the prevalence of pulmonary nontuberculous mycobacteria (NTM) is increasing. Most pulmonary NTM infections are caused by the Mycobacterium avium complex (MAC). Sadly, the treatment of pulmonary MAC is suboptimal with failure rates ranging from 37% to 58%. Therefore, there is a need to develop new therapeutics. Developing new immunotherapies and studying their interaction with standard or new drugs requires reliable assays. Four different assays including CFSE-based flow cytometry, in vitro protection assays, IFN-γ ELISPOT, and murine infection models were optimized using a reference strain of MAC (ATCC 700898) to help with the development of immunotherapies for MAC. Expansion of proliferating and IFN-γ producing human T cells is optimal after 7 days of stimulation with MAC at a multiplicity of infection (MOI) of 0.1, achieving a stimulation index of 26.5 ± 11.6 (mean ± SE). The in vitro protection assay for MAC works best by co-culturing T cells expanded for 7 days with MAC (MOI 1)-infected autologous macrophages. Aerosol MAC infection of mice allows measurement of the effects of the BCG vaccine and clarithromycin. IFN-γ ELISPOT assays with live MAC (MOI 3) stimulation of splenocytes from mice immunized with BCG help identify differences between unimmunized mice and mice immunized with BCG. In conclusion, multiple assays are available for use to identify MAC-specific effector T cells, which will help in the development of new therapeutics or vaccines against pulmonary MAC.

Double Trouble: Pulmonary Nontuberculous Mycobacteria (Mycobacterium fortuitum) Unveiled in a Successfully Treated Tuberculosis Survivor: A Case Report

Double Trouble: Pulmonary Nontuberculous Mycobacteria (Mycobacterium fortuitum) Unveiled in a Successfully Treated Tuberculosis Survivor: A Case Report

Evaluation of the GenoType NTM-DR line probe assay for nontuberculous mycobacteria using whole genome sequences as reference standard

Pulmonary nontuberculous mycobacteria (NTM) disease is an emerging public health challenge that is especially problematic in people with cystic fibrosis (CF). Effective treatment depends on accurate species and subspecies identification and antimicrobial susceptibility status. We evaluated the GenoType NTM-DR VER 1.0 assay using biobanked NTM isolates with whole genome sequence (WGS) data and control isolates (total n=285). Species and subspecies detection sensitivity and specificity were 100 % for all species and subspecies except for two subspecies of M. intracellulare, that demonstrated a small degree of discrepant identification between M. intracellulare subspecies intracellulare and subspecies chimaera. All antimicrobial resistance markers were identified with 100 % sensitivity and specificity.We conclude that the GenoType NTM-DR assay offers a rapid and accurate option for identifying the most frequently encountered pathogenic NTM taxa and drug resistance markers.SUPPORT: Colorado CF Research Development Program and Colorado CF National Resource Centers funded by the Cystic Fibrosis Foundation, NJH Advanced Diagnostics Laboratories, Colorado Advanced Industries Accelerator Grant

Clinical Significance, Species Distribution, and Temporal Trends of Nontuberculous Mycobacteria, Denmark, 1991-2022.

Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity.

Successful Removal of a Boiled Soybean Using Flexible Bronchoscopy

Background: In developed countries, the number of patients experiencing aspiration for foreign bodies is increasing due to the aging population. Most cases are managed with flexible bronchoscopy; however, training is challenging for many bronchoscopists because of the limited number of available facilities and the few opportunities to perform the procedure. Case Presentation: An 87-year-old patient with a history of pulmonary non-tuberculous mycobacteria was admitted to our hospital for bacterial pneumonia. The day after admission, the patient reported aspirating a boiled soybean during breakfast. A chest computed tomography revealed an oval shadow, approximately 10 mm in size, in the bronchus of the right lower lobe, suspected to be the aspirated soybean. Using a flexible bronchoscope, we successfully removed the boiled soybean with a brush, curettage, and basket forceps without complications. Conclusions: There is no standardized method for removing foreign bodies; the procedure should be adapted according to the type of foreign body, the site of obstruction, cost, and the medical resources available in the hospital.

Micobacterias no tuberculosas: cuando categorizarlas en pediatría

Background: The term "nontuberculous mycobacteria" refers to more than 170 different species of bacteria that are not Mycobacterium tuberculosis or M. leprae. These bacteria can cause a variety of infections in children. Accurate diagnosis is crucial, as they can be confused with other diseases. Treatment can be challenging due to antibiotic resistance in some strains. The literature review focuses on improving the diagnosis and treatment of these infections in the pediatric population. The characterization of these bacteria, through methods such as PCR, is essential for effective treatment. Material and methods: A systematic review was performed to determine the need to categorize nontuberculous mycobacteria in pediatrics. Various databases and Boolean operators were used to search for relevant information. Inclusion and exclusion criteria were applied to select documents. The review covered the period from 2012 to 2023. They focused on pediatric studies on nontuberculous mycobacteria. Results: The article "Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis" describes a case of juvenile laryngeal papillomatosis (JLP) that was complicated by idiopathic CD4 lymphocytopenia (ICL). Despite treatments and surgeries, JLP progressed. The patient developed ICL based on the decrease in CD4+ lymphocytes without HIV. After receiving interferon-alpha with partial response, he died. The study "Prevalence and species spectrum of both pulmonary and extrapulmonary nontuberculous mycobacteria isolates" highlights the high prevalence of nontuberculous mycobacteria in India, especially M. abscessus. "Nontuberculous Mycobacteria in Denmark" evaluates the incidence and clinical relevance of NTM in Denmark from 1991 to 2015, finding a stable incidence and differences in age groups and species. These studies enrich the understanding of these medical conditions. Conclusion: The four studies analyzed offer a global vision of the incidence and characteristics of nontuberculous mycobacteria (NTM) in various regions. Although they all address NTM, they reveal geographic variability in their incidence and characteristics. A global increase in the incidence of NTM is observed, raising concerns about its clinical relevance. Furthermore, the study in New York highlights the increase in NTM in densely populated urban environments. Botswana underlines the importance of accurate diagnosis, especially in areas with high prevalence of tuberculosis and HIV. In Denmark, no significant increase in the incidence of NTM is observed, suggesting regional variability. Together, these findings emphasize the need to understand the local epidemiology of NTM and the importance of its prevention and control

Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.

Nationwide Increasing Incidence of Nontuberculous Mycobacterial Diseases Among Adults in Denmark: Eighteen Years of Follow-Up

BackgroundThe epidemiology of nontuberculous mycobacteria (NTM) infections is not well described. In this study, we determined the incidence and prevalence of NTM infections and focused on social risk factors. Additionally, we described persons suffering from pulmonary and extrapulmonary NTM. Research questionWhat is the incidence and prevalence of NTM and what are the characteristics of the affected patients? MethodsThis is a nationwide retrospective register-based cohort study in Denmark. Adult patients with NTM diagnosis in the Danish national registers from 2000-2017 were classified as having either pulmonary or extrapulmonary NTM disease. ResultsWe identified 1,146 adults with an NTM diagnosis. 661 patients had pulmonary NTM of which 50.4% were male, while 485 had extrapulmonary NTM of which 59.6% were male. The median age (Interquartile range), was 66 years (18) and 57 years (32), respectively. The yearly incidence rate per 100,000 increased between 2000 and 2017 for both pulmonary (0.4 to 1.3) and extrapulmonary NTM (0.3 to 0.6). The annual prevalence per 100,000 increased from 0.4 to 3.5 for pulmonary and 0.3 to 1.0 for extrapulmonary NTM. The incidence rate increased with age. The incidence of pulmonary NTM was highest in 70+ year-olds (19.3 per 100,000). Compared to pulmonary NTM patients, extrapulmonary NTM patients were more likely to be employed and had a higher educational level. InterpretationThe prevalence of NTM disease in Denmark increased between 2000 and 2017. Pulmonary and extrapulmonary NTM patients are two distinct groups that differ in age, gender, education, and employment status. Increased suspicion of pulmonary NTM disease is warranted in the elderly after exclusion of more common lung infections.

Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei

The objective of this study was to examine the association between the lung lobe-deposited dose of inhaled fine particulate matter (PM2.5) and chest X-ray abnormalities in different lung lobes of pulmonary tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB), and non-tuberculosis mycobacteria infections (NTM). A cross-sectional study was conducted between 2014 and 2022, comprising 1073 patients who were recruited from chest department clinic in a tertial refer hospital in Taipei City, Taiwan. Ambient 1-, 7-, and 30-day PM2.5 exposure and the deposition of PM2.5 in different lung lobes were estimated in each subject. The β coefficient for PM2.5 and deposited PM2.5 in lungs with the outcome variables (pulmonary TB, MDR-TB, and NTM infection) was derived through regression analysis and adjusted for age, gender, BMI, smoking status, and family income. We observed that a 1 μg/m3 increase in ambient PM2.5 was associated with an increase of MDR-TB infections of 0.004 times (95%CI: 0.001–0.007). A 1 μg/m3 increase in 1-day and 7-day PM2.5 deposition in left upper lobe and left lower lobe was associated with an increase in chest X-ray abnormalities of 9.19 % and 1.18 % (95%CI: 0.87–17.51 and 95%CI: 0.08–2.28), and 4.52 % and 5.20 % (95%CI: 0.66–8.38 and 95%CI: 0.51–9.89) in left lung of TB patients, respectively. A 1 μg/m3 increase in 30-day PM2.5 deposition in alveolar region was associated with an increase in percent abnormality of 2.50 % (95%CI: 0.65–4.35) in left upper lobe and 3.33 % (95%CI: 0.65–6.01) in right middle lobe, while in total lung was 0.63 % (95%CI: 0.01–1.27) in right upper lobe and 0.37 % (95%CI, 0.06–0.81) in right lung of MDR-TB patients. Inhaled PM2.5 deposition in lungs was associated with an exacerbation of the radiographic severity of pulmonary TB, particularly in pulmonary MDR-TB patients in upper and middle lobes. Particulate air pollution may potentially exacerbate the radiographic severity and treatment resistance in individuals with pulmonary TB.

Epidemiological and clinical characteristics of nontuberculous mycobacterial infections: A retrospective female cohort study in an Italian population

ObjectivesThis study aims to assess the characteristics and treatment outcomes of patients diagnosed with non-tuberculous mycobacteria (NTM) diseases at the Infectious Diseases Unit of ARNAS Garibaldi Hospital in Catania, Italy, focusing on demographics, clinical features, and treatment effectiveness. MethodsWe conducted a retrospective observational study of 10 patients diagnosed with NTM diseases between 2019 and 2021. Data was collected from electronic medical records, including demographic information, comorbidities, treatment modalities, and outcomes. The study utilized descriptive statistics to analyze continuous and categorical variables. Treatment regimens were based on individual patient needs, incorporating a combination of antibiotics. ResultsThe median age of the patients was 55.44 years, all female, predominantly suffering from pulmonary NTM diseases. Mycobacterium intracellulare was the most common pathogen. Common comorbidities included COPD, bronchiectasis, GERD, and hypovitaminosis D. Patients showed symptoms like fever, cough, and asthenia. The treatment regimens were diverse, with macrolides, rifampicin, and ethambutol forming the core. Adverse effects were noted in 40 % of patients, including gastrointestinal and neurological disorders. All patients achieved microbiological cure, with 60 % showing clinical improvement and 36 % radiological improvement. ConclusionThe study highlights the complexity of diagnosing and treating NTM diseases, emphasizing the need for personalized treatment plans and vigilant monitoring of adverse effects. Despite achieving microbiological cure, challenges remain in achieving complete clinical and radiological resolution. Further research is needed to enhance the understanding and management of NTM diseases, particularly in diverse populations.

Intracellular iron accumulation facilitates mycobacterial infection in old mouse macrophages

Aging has a significant impact on the immune system, leading to a gradual decline in immune function and changes in the body’s ability to respond to bacterial infections. Non-tuberculous mycobacteria (NTM), also known as atypical mycobacteria or environmental mycobacteria, are commonly found in soil, water, and various environmental sources. While many NTM species are considered opportunistic pathogens, some can cause significant infections, particularly in individuals with compromised immune systems, such as older individuals. When mycobacteria enter the body, macrophages are among the first immune cells to encounter them and attempt to engulf mycobacteria through a process called phagocytosis. Some NTM species, including Mycobacterium avium (M. avium) can survive and replicate within macrophages. However, little is known about the interaction between NTM and macrophages in older individuals. In this study, we investigated the response of bone marrow–derived macrophage (BMMs) isolated from young (5 months) and old (25 months) mice to M. avium serotype 4, one of the main NTM species in patients with pulmonary NTM diseases. Our results demonstrated that BMMs from old mice have an increased level of intracellular iron and are more susceptible to M. avium serotype 4 infection compared to BMMs from young mice. The whole-cell proteomic analysis indicated a dysregulated expression of iron homeostasis–associated proteins in old BMMs regardless of mycobacterial infection. Deferoxamine, an iron chelator, significantly rescued mycobacterial killing and phagolysosome maturation in BMMs from old mice. Therefore, our data for the first time indicate that an intracellular iron accumulation improves NTM survival within macrophages from old mice and suggest a potential application of iron-chelating drugs as a host-directed therapy for pulmonary NTM infection in older individuals.

Incorporating direct molecular diagnostics in management algorithms for nontuberculous mycobacteria: Is it high time?

Nontuberculous mycobacteria (NTM) are a group of acid-fast mycobacteria other than Mycobacterium tuberculosis complex (MTBC) that cause pulmonary disease that is similar to the disease caused by MTBC. International guidelines for the diagnosis of pulmonary NTM disease are rigid and have remained unchanged for nearly 2 decades. In this opinion piece, we provide a new perspective on the traditional criteria by suggesting a diagnostic algorithm that incorporates direct molecular identification of NTM performed on raw sputum specimens (using Sanger or targeted deep sequencing approaches, among others) paired with traditional culture methods. Our approach ensures a more rapid diagnosis of pulmonary NTM disease, thus, facilitating timeous clinical diagnosis, and prompt treatment initiation, where indicated, and leverages recent advances in novel molecular techniques into routine NTM identification practice.

Concomitant or sequential pulmonary infection with non-tuberculous mycobacteria and Aspergillus.

Non-tuberculous mycobacteria (NTM) and Aspergillus are ubiquitous organisms that have the potential to cause significant pulmonary disease in certain clinical contexts. An association is known to exist between NTM and Aspergillus lung infections. However, it is unclear if NTM infection predisposes to Aspergillus infection or vice versa. It is also unclear whether treatment for one results in a favourable ecological niche that facilitates the growth of the other and promotes subsequent clinical disease. An improved understanding of the link between these two pulmonary pathogens is critical to guide improvements in clinical practice, and ultimately, enhance outcomes among patients who are at risk of experiencing these infections, either concomitantly or sequentially. Here, we discuss the association between pulmonary NTM and Aspergillus infections. We address the frequency with which coinfection or sequential infections are reported to occur, predisposing risk factors that have been identified and the impact on clinical outcomes. Current data on the mechanistic links between NTM and Aspergillus lung infections are also considered. The potential implications for routine clinical practice are explored.

A Japanese retrospective study of non-tuberculous mycobacterial infection in children, adolescents, and young adult patients with hematologic-oncologic diseases.

Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients were identified: 21 patients with hematopoietic stem cell transplantation (HSCT) and 15 non-transplant patients. Post-transplant patients were infected with NTM at 24 sites, including the lungs (N=12), skin and soft tissues (N=6), bloodstream (N=4), and others (N=2). Nine of 12 patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GvHD), and rapid-growing mycobacteria (RGM) were isolated from 5 of them. In non-transplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; N=5), inborn errors of immunity (IEI; N=6), and others (N=4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, 3 typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GvHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GvHD, who may require active screening for NTM.

Evaluating Diagnostic Utility of geneXpert Ultra (Mycobacterium tuberculosis/Rifampicin), Microscopy and Liquid Culture to Isolate Mycobacterium tuberculosis and Nontuberculous Mycobacteria among Pulmonary Tuberculosis Suspects

CONTEXT: Nontuberculous mycobacteria (NTM) are posing major public health problems and have recently gained importance as they are being isolated from patients with pulmonary disorders. Most of the time, NTM are misinterpreted as tuberculosis (TB) and this misdiagnosis leads to treatment failure. Hence, this study aimed to identify NTMs isolated from suspected cases of pulmonary TB cases and was aimed to distinguish Mycobacterium TB (MTB) from NTM infections. AIMS: Our study aimed to compare microscopy grading of respiratory samples with the Ct values of GeneXpert Ultra (MTB/rifampicin [RIF]), to assess the diagnostic accuracy of microscopy, GeneXpert ultra (MTB/RIF), liquid culture, to compare GeneXpert ultra (MTB/RIF) results with microscopy with culture and clinical implications, importance of performing a rapid test for pulmonary TB and pulmonary NTM infections in suspected cases of adults. SETTINGS AND DESIGN: The study was conducted in the Mycobacteriology laboratory, Department of Microbiology, in Kasturba Hospital, Manipal. The study was a prospective, cross-sectional study, single center. SUBJECTS AND METHODS: A total of 452 respiratory samples obtained from April to July 2023 were included in the study. Smearpositive pulmonary TB cases were identified and subjected to amplification by GeneXpert ultra (MTB/RIF) and 84 samples were GeneXpert ultra (MTB/RIF) positive and RIF sensitive. Liquid culture by mycobacteria growth indicator tube (MGIT) 960 was performed and for positive tubes, TB Ag MPT64 was performed. The results were compared and analyzed with patients’ demographic information. Clinical and radiological data from the requisition forms were assessed. STATISTICAL ANALYSIS USED: IBM SPSS statistics software version 22 was used. Correlations between GeneXpert ultra (MTB/RIF) Ct values and smear status were calculated by polychoric correlation. Extended McNemar’s test was used to find the association between the variables. RESULTS: GeneXpert ultra (MTB/RIF) yielded a positivity rate of 22.2% compared to smear microscopy 17.2%. Liquid culture yielded a positivity rate of 20.3%. Ct value and smear grading yielded a positive correlation (ρ = 0.8681; P < 0.05). Undetected cases of TB by GeneXpert ultra (MTB/RIF) were identified as positive under liquid culture by MGIT 960. TB Ag MPT64 was performed and yielded NTM and speciated as Mycobacterium abscessus complex by line probe assay. CONCLUSIONS: Our study states the need for identification and differentiation of MTB from NTM.

Long-term evaluation of clinical success and safety of omadacycline in nontuberculous mycobacteria infections: a retrospective, multicenter cohort of real-world health outcomes.

Infections due to nontuberculous mycobacteria (NTM) continue to increase in prevalence, leading to problematic clinical outcomes. Omadacycline (OMC) is an aminomethylcycline antibiotic with FDA orphan drug and fast-track designations for pulmonary NTM infections, including Mycobacteroides abscessus (MAB). This multicenter retrospective study across 16 U.S. medical institutions from January 2020 to March 2023 examined the long-term clinical success, safety, and tolerability of OMC for NTM infections. The cohort included patients aged ≥18 yr, who were clinically evaluable, and` had been treated with OMC for ≥3 mo without a previous diagnosis of cystic fibrosis. The primary outcome was 3 mo clinical success, with secondary outcomes including clinical improvement and mortality at 6- and 12 mo, persistence or reemergence of infection, adverse effects, and reasons for OMC utilization. Seventy-five patients were included in this analysis. Most patients were female (48/75, 64.0%) or Caucasian (58/75, 77.3%), with a median (IQR) age of 59 yr (49-67). Most had NTM pulmonary disease (33/75, 44.0%), skin and soft tissue disease (19/75, 25.3%), or osteomyelitis (10/75, 13.3%), and Mycobacterium abscessus (60/75, 80%) was the most commonly isolated NTM pathogen. The median (IQR) treatment duration was 6 mo (4 - 14), and the most commonly co-administered antibiotic was azithromycin (33/70, 47.1%). Three-month clinical success was observed in 80.0% (60/75) of patients, and AEs attributable to OMC occurred in 32.0% (24/75) of patients, leading to drug discontinuation in 9.3% (7/75).

Clinical characteristics of extrapulmonary nontuberculous mycobacteria infections in comparison with pulmonary infections: A single-center, retrospective study in Japan

IntroductionThe prevalence of nontuberculous mycobacteria (NTM) infections is increasing worldwide. Although NTM can affect extrapulmonary organs, studies on the clinical characteristics of extrapulmonary NTM are rare. MethodsWe retrospectively analyzed patients who were newly diagnosed with NTM infections at Hiroshima University Hospital between 2001 and 2021 to investigate species distribution, infected sites, and risk factors of extrapulmonary NTM compared to pulmonary NTM. ResultsOf the 261 NTM infections, 9.6% and 90.4% had extrapulmonary and pulmonary NTM, respectively. The mean ages of patients with extrapulmonary and pulmonary NTM were 53.4 and 69.3 years, 64.0% and 42.8% were male, 36.0% and 9.3% received corticosteroids, 20.0% and 0% had acquired immune deficiency syndrome (AIDS), and 56.0% and 16.1% had any immunosuppressive conditions, respectively. Younger age, corticosteroid use, and AIDS were associated with extrapulmonary NTM. In pulmonary NTM, Mycobacterium avium complex (MAC) accounted for 86.4% of NTM species, followed by M. abscessus complex (4.2%), whereas in extrapulmonary NTM, M. abscessus complex, MAC, M. chelonae, and M. fortuitum accounted for 36.0%, 28.0%, 12.0%, and 8.0%, respectively. Compared to pulmonary NTM, extrapulmonary NTM were significantly more likely to be rapid-growing mycobacteria (RGM) (56.0% vs. 5.5%). The most common sites of infection were the skin and soft tissues (44.0%), followed by the blood (20.0%), tenosynovium, and lymph nodes (12.0%). ConclusionYounger age and immunosuppressive conditions are associated with extrapulmonary NTM, with a higher prevalence of RGM in extrapulmonary NTM than in pulmonary NTM. These results provide a better understanding of extrapulmonary NTM.

Rifaximin potentiates clarithromycin against Mycobacterium abscessus in vitro and in zebrafish.

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) that causes chronic pulmonary infections. Because of its extensive innate resistance to numerous antibiotics, treatment options are limited, often resulting in poor clinical outcomes. Current treatment regimens usually involve a combination of antibiotics, with clarithromycin being the cornerstone of NTM treatments. To identify drug candidates that exhibit synergistic activity with clarithromycin against M. abscessus. We performed cell-based phenotypic screening of a compound library against M. abscessus induced to become resistant to clarithromycin. Furthermore, we evaluated the toxicity and efficacy of the top compound in a zebrafish embryo infection model. The screen revealed rifaximin as a clarithromycin potentiator. The combination of rifaximin and clarithromycin was synergistic and bactericidal in vitro and potent in the zebrafish model. The data indicate that the rifaximin/clarithromycin combination is promising to effectively treat pulmonary NTM infections.

Association of pulmonary nontuberculous mycobacteria with the outcomes of patients with lung cancer: A retrospective matched cohort study with a special emphasis on the impact of chemotherapy.

Nontuberculous mycobacteria (NTM) may be present in the respiratory tract of patients with lung cancer. We investigated the association of pulmonary NTM with the clinical features and outcomes of patients with lung cancer. Between 2015 and 2019, the data of patients diagnosed with lung cancer at a medical center in northern Taiwan were analyzed. Patients whose respiratory specimens were culture-positive for NTM were identified (NTM group). For each patient in the NTM group, a matched control was selected (control group). The survival of the two groups was compared using the Kaplan-Meier method and Cox proportional hazards regression analysis. Among 8718 patients with lung cancer, 5418 (62.1%) underwent a sputum mycobacterial culture. At least one NTM species was isolated from 138 (2.5%) patients. The median age was 72 years (range: 64-80). In the NTM group, 19.8% fulfilled both the microbiological and radiographic criteria for the diagnosis of NTM lung disease. Compared with the control group, the NTM group exhibited a lower body mass index (22.4 vs. 23.6, p=0.025) and a higher prevalence of structural lung disease (38.9% vs. 22.2%, p=0.004). The two-year survival was not significantly different between the two groups (hazard ratio [HR]: 1.110; 95% confidence interval [CI]: 0.702-1.754, p=0.656). In patients receiving chemotherapy, pulmonary NTM was associated with worse survival (HR: 2.497, 95% CI: 1.262-4.943, p=0.009). Except in patients receiving chemotherapy, pulmonary NTM may not be clinically relevant in patients with lung cancer.