Nontuberculous Mycobacteria Patients Research Articles

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.

Accuracy of QuantiFERON in active tuberculosis suspects with comorbidities and nontuberculous mycobacterial infection in Northern California.

The QuantiFERON-TB Gold (QFT) is routinely utilized in North American health systems to detect a cellular immune response to Mycobacterium tuberculosis antigens in symptomatic and asymptomatic patients. The sensitivity of QFT in tuberculosis (TB) patients with comorbidities is not well established and the specificity of QFT in patients with nontuberculous mycobacteria (NTM) infections is incompletely understood. Between 2012 and 2023, all patients with culture-positive TB and patients with NTM infection per the expert diagnostic guidelines or biopsy-proven NTM infection who had a concurrent QFT test were included in this study. The sensitivity and specificity of QFT were measured in TB and NTM patients, respectively. In 109 patients with active TB, the overall sensitivity of QFT was 78.0% (85/109; 95% CI: 70.1, 85.7). The sensitivity was 86.0% (49/57; 95% CI: 76.6, 94.8) and 69.2% (36/52; 95% CI: 56.7, 81.8) in immunocompetent and immunocompromised patients, respectively. The overall specificity of QFT in 88 patients with NTM infection was 76.1% (67/88; 95% CI: 67.2, 85.0). After the exclusion of 17 NTM patients with risk factors for latent TB infection, the specificity was 94.4% (67/71; 95% CI: 89.1, 99.7). Two patients had NTM species known to cross-react with QFT. In two NTM patients infected with species (Mycobacterium intracellulare subsp. intracellulare and Mycobacterium intracellulare subsp. chimaera) not known to cross-react, whole genome sequencing did not detect ESAT-6 or CFP-10. In Northern California, the QFT assay demonstrated moderately low to moderately high sensitivity in TB patients and very high specificity in NTM patients, thus ruling out concerns for cross-reactivity with NTM.

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

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. We retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years. 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. 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.

Hematological profiles of patients with tuberculosis and nontuberculous mycobacteria infections in Bamako, Mali.

Pulmonary tuberculosis (TB) remains one of the main causes of morbidity and mortality in Mali. Nontuberculous mycobacteria (NTM) infections are very common but are often cofounded with TB because of the similarity of symptoms, which makes the diagnosis difficult. Hematological abnormalities associated with TB have been described, but not with NTM. Therefore, the goal of this study was to compare the hematological parameters of patients infected with TB and NTM infections. A cross-sectional study enrolling TB and NTM participants was conducted in 2018-2020. Five milliliters of venous blood and sputum samples were collected from each participant to determine the hematological parameters using the RUBY CELL-DYN Ruby Version 2.2 ML. A BACTEC MGIT 960 and multiplex reverse transcription-polymerase chain reaction were used to distinguish Mycobacterium tuberculosis from NTM, respectively. Of the total 90 patients enrolled, there was a decrease in hemoglobin and hematocrit levels in both the groups (P = 0.05). In addition, we found that the percentages of basophil cells (P = 0.01) and mean values of platelets (P = 0.04) were significantly higher in TB patients than those of NTMs. Moreover, the mean of absolute values of eosinophil cells of TB patients was significantly lower than those of NTMs (P = 0.03). We found significant statistical differences in basophils, platelets, and eosinophils in differentiating TB and NTM in this pilot study. Future studies with patients at different clinical stages are needed to confirm the hematological profiles of TB and NTM patients.

Screening and Drug Resistance Analysis of Non-Tuberculous Mycobacteria in Patients with Suspected Pulmonary Tuberculosis on the Hainan Island, China

China has seen a drastic increase in the incidence of non-tuberculous mycobacteria (NTM) infection, which is a notable public health issue. Due to a lack of reliable epidemiological surveillance information, there is a need to gather accurate epidemiological and surveillance data, which can help clinicians effectively treat NTM patients. Moreover, drug susceptibility testing for NTM is not frequently performed in China. This retrospective study, therefore, determined the prevalence and resistance characteristics of NTM to provide a reference to control the NTM epidemic. Sputum, alveolar lavage fluid, and other respiratory specimens were collected from 3025 patients with suspected pulmonary tuberculosis attending The Second Affiliated Hospital of Hainan Medical University from January 2014 to December 2021. Strain identification and species distribution of NTM were performed by DNA chip technology and gene sequencing, and the drug resistance of NTM isolates was evaluated by calculating the minimum inhibitory concentration through antimicrobial susceptibility testing for NTM. From 2014 to 2021, 373 strains of NTM were isolated and identified from respiratory specimens of 3025 suspected tuberculosis patients. Except in 2014, NTM-infected patients accounted for more than 10% of suspected tuberculosis patients in other years. The median age of patients with NTM infection was 62.0 years (53.0, 71.0), and the male-to-female ratio among these patients was 0.79:1. Among culture-positive strains, 12.3% (373/3040; 95% CI 11.1-13.4%) were identified as NTM comprising forty species of NTM. The forty species of NTM included 23 slow-growing mycobacteria (SGM) and 17 rapidly-growing mycobacteria (RGM). Among the NTM isolates, 58.7% (219/373; 95% CI 53.7-63.7%) were SGM and 41.3% (154/373; 95% CI 36.3-46.3%) were RGM. M.avium complex(MAC)(41.3%; 95% CI 36.3-46.3%) and M.abscessus complex (MABC)(33.2%; 95% CI 28.4-38.0%) were the most frequently detected species, followed by M.simiae Complex (11.8%; 95% CI 8.5-15.1%), M.fortuitum group (5.1%; 95% CI 2.9-7.3%), and others. Drug sensitivity test results showed that most of the NTM isolates were susceptible to amikacin and clarithromycin with a drug resistance rate of less than 10%. However, clarithromycin could induce drug resistance, followed by linezolid and moxifloxacin, and their drug resistance rate was less than 50%. During 2014-2021, the number of NTM isolates detected in the respiratory specimens of the study patients in The Second Affiliated Hospital of Hainan Medical University increased year by year. M. intracellulare is the most common pathogenic NTM species, and there is a high incidence of NTM infection on Hainan Island. Our findings might be of great importance for diagnosing and treating this patient population in Hainan.

A glimpse into the genotype and clinical importance of non tuberculous mycobacteria among pulmonary tuberculosis patients: The case of Ethiopia.

Laboratory identification of nontuberculous mycobacteria (NTM) species is not regularly performed while, they have a public health importance with a prevalence of more than 5% among pulmonary tuberculosis (PTB) patients in Ethiopia. Hence, this study aimed to identify the NTM species and their clinical significance among PTB patients. A retrospective study was conducted at the Ethiopian Public Health Institution’s (EPHI’s) national TB referral laboratory. Stored NTM isolates were genotyped using GenoType Mycobacterium CM/AS kit (Hain Life science, Germany). Data pertinent to the study was extracted from the EPHI’s database and patients’ medical records. Between January 2 & December 28 of 2017, a total of 3,834 samples were processed from 698 TB patients of whom 50% were female. Among 3,317 samples with mycobacterial culture results 7.3% were NTM and majority of them were identified from smear negative TB patients. M. simiae was the /predominant NTM among the genotyped isolates. All the studied NTM species were not clinically important however, considering the similarity of clinical and radiologic findings between NTM and MTBC infected patients, integrating NTM species identification in the routine TB laboratory diagnosis may augment clinicians’ decision particularly in DR-TB patients. Additional similar prospective study with a larger sample size is recommended. Moreover, urgent improvements on patients’ record keeping practice are required in the studied hospitals.

Clinical Characteristics and Mortality of Non-tuberculous Mycobacterial Infection in Immunocompromised vs. Immunocompetent Hosts.

Immunosuppression and host vulnerability play a key role in non-tuberculous mycobacteria (NTM) pathogenesis. The objective of this study was to compare the clinical characteristics and mortality of NTM infections in immunocompromised and immunocompetent patients. We used a retrospective dataset obtained from our large, tertiary, urban, teaching hospital which is the medical records of hospitalized patients with NTM infections between January 1, 2013 to December 31, 2020. The information including clinical manifestations, imaging, and NTM etiological data were obtained from the hospital's clinical data system. A total of 480 patients with NTM infections completed species identification. 118 hospitalized NTM patients who met ATS/IDSA NTM diagnostic criteria and had complete medical records were included in the study. The average age was 49.4 years, 57 (48.3%) were female, and 64 (54.2%) were immunosuppressed hosts. In our study, the most common species in order of frequency were: M. intracellulare, M. abscessus, M. avium, and M. kansasii among NTM patients. The most common comorbidity was history of previous tuberculosis (30.5%). Besides malignancy, the most common immunodeficiencies were adult-onset immunodeficiency induced by anti-interferon-gamma autoantibody, SLE, and vasculitis. The immunocompromised patients with NTM had more clinical symptoms, comorbidities and lower lymphocyte counts compared to immunocompetent patients. The mortality we observed in immunocompromised patients of NTM disease was significantly higher than that of immunocompetent patients (HR 3.537, 95% CI 1.526–8.362). Immunosuppressed NTM patients with lower B and CD4+ T lymphocyte counts may more frequently present with disseminated NTM infections, clinical exacerbations, and higher mortality than immunocompetent patients.

Prevalence, Strains, and Drug Susceptibility of Nontuberculous Mycobacteria Isolates from Tuberculous Suspects

Background: The prevalence of nontuberculous mycobacteria (NTM) infection has been increasing globally. Many cases of NTM infection are misdiagnosed as Mycobacterium tuberculous (MTB) because of similar clinicoradiological features. Objectives: To determine the burden and characteristics of NTM infection, this study was done to evaluate clinical isolates collected from tuberculous (TB) suspects in a population from Northwest China. Methods: From January to December 2020, the clinical samples of 9,142 TB suspects were collected for the PCR-fluorescent probe and mycobacterial culture. The PCR-fluorescent probe-positive nucleic acid samples were further subjected to a DNA microarray for confirmation and species identification. Drug susceptibility testing (DST) was also carried out using the micropore plate method (MicroDSTTM) on isolates from NTM patients. Results: Of 9,412 TB suspects, 85 cases (0.9%) were clinically diagnosed with NTM infection according to the American Thoracic Society (ATS) guidelines. For the laboratory samples, a total of 169 NTM strains, identified by molecular biology methods, were classified into 10 species. The most common species were M. chelonae/ M. abscessus (64/169, 37.7%) and M. intracellulare (40/169, 23.7%). All strains showed the highest resistance to imipenem/cilastatin (85/85, 100%) and the highest susceptibility to linezolid (4/85, 4.7%). In comparison with the rapidly growing mycobacteria (RGM) group, the slowly growing mycobacteria (SGM) group showed a lower resistance and a shorter hospital inpatient stay (t = 6.66, P < 0.001 and t = 2.40, P = 0.020, respectively). Conclusions: Mycobacterium chelonae/M. abscessus and M. intracellulare were the most frequently detected NTM pathogens in Northwest China. The differences in drug sensitivity and clinical characteristics were giant for different strains. Timely identification and accurate DST play important roles in NTM management.

Analysis of the clinical characteristics and species distribution of non-tuberculous mycobacteria in a general hospital

Objective: To summarize the clinical characteristics and species distribution of nontuberculous mycobacteria(NTM). Methods: We conducted a retrospectively chart review of 453 adult patients with 532 positive cultures with NTM diagnosed and treated in Peking Union Medical College Hospital from January 2014 to December 2018. The information including clinical findings, imaging and etiological data were obtained from clinical examination system. Among these 453 patients, 75 cases met the diagnostic criteria for NTM, with detailed clinical data, culture results and radiological images. Of these patients, 38 were males and 37 were females, with an average age of (50.8±16.2) years. Clinical manifestations, imaging features, NTM species and treatment were analyzed. Results: Among 75 NTM patients, 43 cases (57.3%, 43/75) were infected with Mycobacterium avium Complex (MAC)/intracellular, 18 cases (24.0%, 18/75) with Mycobacterium turtle/abscess, and 7 cases (9.3%, 7/75) with Mycobacterium kansasii. Comorbidities existed in 64.0% patients (48/75). The top two common comorbidities were previous tuberculosis (25.3%, 19/75) infection and clinical bronchiectasis (18.7%, 14/75). After the respiratory disease (82.7%, 62/75), we identified bloodstream as the most frequent manifestation of NTM infection (25.3%, 19/75). MAC was often associated with infection in respiratory system and bloodstream, while rapidly growing mycobacteria (RGM) was more commonly detected in lymph nodes and skin and soft tissues. Cough/expectoration (77.4%, 48/62) was the most common clinical symptom of NTM disease, followed by fever and dyspnea. The frequent imaging findings were nodules (41.9%, 26/62), bronchiectasis (37.1%, 23/62), and fibrous cavities (24.2%, 15/62). In disseminated NTM disease, 94.7% (18/19) patients had underlying diseases and 89.5% (17/19) patients had long-term immunosuppression. Conclusion: The most common NTM species was Mycobacterium avium/intracellular in our series. The predominant infected organ was the respiratory system. Previous tuberculosis history likely increased the risk of infection.

Nontuberculous Mycobacteria in the Biofilm Microbiome of Private Well and Premise Plumbing

Household plumbing biofilms can harbor and transmit bacterial pathogens. Pulmonary infections by nontuberculous mycobacteria (NTM) can occur from this transmission route. NTM infections are increasing around the world and in New Jersey (NJ), where this field study was performed. Plumbing biofilm samples were collected from sinks and showerheads in homes using private wells (n = 19) and in homes of NTM patients (n = 5). DNA extracts were analyzed by quantitative polymerase chain reaction (qPCR) to quantify mycobacterial marker genes and by amplicon sequencing to describe the microbiomes where NTM were observed. Water samples were analyzed for basic water quality parameters and fecal indicator organisms. Participants completed surveys about their wells and home water systems to enable testing of potential relationships between these environmental factors and the microbial communities. NTM were observed in more than half of private well biofilm samples using qPCR and in all of the selected samples analyzed by amplicon sequencing (n = 29/70), even when below detection by qPCR. Samples from patient homes, most of whom used public water supply, had similar abundances of NTM as samples from private wells. Physiography and within-home location (e.g., kitchen sink) explained some variation in concentrations of mycobacteria genes. One microbial family with no known human pathogens, Rikenellaceae, was identified as a potential antagonist to mycobacteria using linear discriminant analysis effect size (LEfSe). This study illuminates the widespread nature of NTM in private well water systems without disinfection selection pressures, and works toward understanding ecological interactions that may aid or slow the growth of NTM toward ecological engineering of healthy plumbing microbiomes.

Genetic Analysis of Korean Adult Patients with Nontuberculous Mycobacteria Suspected of Primary Ciliary Dyskinesia Using Whole Exome Sequencing.

PurposeNontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD.Materials and MethodsWES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCD-candidate genes, and 990 ciliome genes were analyzed.ResultsFour patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114, DNAH5, HYDIN, and NME5. In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants.ConclusionAt least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD.

Evaluation of plasma anti-GPL-core IgA and IgG for diagnosis of disseminated non-tuberculous mycobacteria infection.

Detection of IgA antibody against Mycobacterium avium complex (MAC) glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC pulmonary disease but has yet to be tested in disseminated Non-tuberculous mycobacteria (NTM) infection. In this study, we address the diagnostic efficacies of an anti-GPL-core ELISA kit in disseminated lymphadenopathy patients positive for NTM culture and anti-IFN-γ autoantibodies. The study was conducted in a tertiary referral center in northeastern Thailand and patients with NTM, tuberculosis, melioidosis, and control subjects were enrolled. Plasma immunoglobulin A (IgA) and G (IgG) antibodies against GPL-core were detected in the subjects and the specificity and sensitivity of the assay was assessed. Anti-GPL-core IgA and IgG levels were significantly higher in NTM patients than other groups (p < 0.0001). Diagnostic efficacy for NTM patients using anti-GPL-core IgA cut-off value of 0.352 U/ml showed good sensitivity (91.18%) and intermediate specificity (70.15%). Using a cut-off value of 4.140 AU/ml for anti-GPL-core IgG showed the same sensitivity (91.18%) with increased specificity (89.55%) and an 81.58% positive predictive value. Most patients with moderate levels (4.140-7.955 AU/ml) of anti-GPL-core IgG had rapidly growing mycobacteria (RGM) infection. Taken together, the detection of anti-GPL-core antibodies could provide a novel option for the diagnosis and management of disseminated NTM infected patients.

Reduction in Expected Survival Associated With Nontuberculous Mycobacterial Pulmonary Disease.

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.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

Outcomes of HIV-positive patients with non-tuberculous mycobacteria positive culture who received anti-tuberculous treatment in Botswana: Implications of using diagnostic algorithms without non-tuberculous mycobacteria.

BackgroundPatients with non-tuberculous mycobacteria (NTM) or Mycobacterium tuberculosis (MTB) pulmonary disease may have similar clinical presentation. The potential for misdiagnosis and inappropriate treatment exists in settings with limited testing capacity for Xpert® MTB/RIF (Xpert), phenotypic culture and NTM speciation. We describe treatment outcomes among people living with HIV (PLHIV) who received anti-tuberculosis treatment and were found to have NTM or MTB positive sputum cultures.MethodsPLHIV attending one of the 22 participating HIV clinics, who screened positive for ≥1 tuberculosis (TB) symptoms (cough, fever, night sweats, or weight loss) were asked to submit sputa for culture and speciation from August 2012 to November 2014. The national intensified TB case finding algorithms were followed: initially symptomatic patients were evaluated by testing sputum samples using a smear (smear-based TB diagnostic algorithm) and, after GeneXpert instruments were installed, by testing with Xpert (Xpert-based TB diagnostic algorithm). Within the study period, TB diagnostic algorithms used for MTB did not include screening, diagnosis, and management of NTM. Despite MTB negative culture, some symptomatic patients, including those with NTM positive culture, received empirical anti-TB treatment at the discretion of treating clinicians. Per the World Health Organization treatment outcomes classification: died, treatment failure or loss-to-follow-up were classified as unfavorable (unsuccessful) outcome; cured and treatment completed were classified as favorable (successful) outcome. Empiric treatment was defined as initiating treatment without or before receiving a test result indicating MTB. We compare treatment outcomes and characteristics among patients with NTM or MTB positive culture who received anti-TB treatment.ResultsAmong 314 PLHIV, who were found co-infected with TB, 146 cases had microbiological evidence; and for 131/146 MTB positive cultures were reported. One-hundred fifty-two of the 314 were clinically diagnosed with TB and treated empirically. Among those empirically treated for TB, 36/152 had culture results positive for NTM, and another 43/152 had culture results positive for MTB, reported after patients received empirical anti-TB treatment. Overall, MTB positive culture results were reported for 174 (131 plus 43) patients. Treatment outcomes were available for 32/36 NTM and 139/174 MTB; unfavorable outcomes were 12.5% and 8.7% for NTM and MTB, respectively, p = 0.514, respectively. For 34/36 tested NTM patients, all Xpert results indicated ‘no MTB’. Among patients who initially received empiric anti-TB treatment and ultimately were found to have MTB positive culture, the unfavorable outcome was 11.8% (4/34), compared to 12.5% (4/32) of patients with NTM positive culture, Fisher’s exact test p = 1.00.ConclusionsWhile the higher unfavorable outcome was non statistically significant, the impact of inappropriate treatment among NTM patients should not be overlooked. Our findings suggest that Xpert has the potential to rapidly rule-out NTM and avoid sub-optimal treatment; further research is needed to evaluate such potential.

4224 Development of a Patient Registry and Biospecimen Repository to Identify Biomarkers in Nontuberculous Mycobacteria Lung Disease

OBJECTIVES/GOALS: Non-tuberculous mycobacteria (NTM) is an emerging infection in the United States. Therapeutic development is impaired in NTM due to lack of biomarkers associated with disease activity and treatment response. To address this, we established a cross-sectional patient registry and biorepository from NTM patients. METHODS/STUDY POPULATION: Beginning August 2019 patients were recruited in a cross-sectional format from the bronchiectasis and NTM clinics at our institution. All patients provided at least one sputum sample in the six months prior to inclusion. Clinical and epidemiologically relevant data was obtained, patient reported outcome measures including the SGRQ were provided, and blood specimens were processed and preserved. Patients were grouped based on clinical phenotype and descriptive statistics were reported as means and standard deviations. Serum inflammatory profiles will be analyzed using standard Luminex assays. RESULTS/ANTICIPATED RESULTS: 72 patients with prior NTM isolation from sputum have been recruited including 28 patients that do not meet ATS guidelines for NTM treatment (colonized), 29 patients are currently receiving treatment, and 15 patients that have a history of completing therapy. Among all NTM patients, the mean age was 59.5 ±17.6 years and 80.8% were female. The mean FEV1 percent predicted among these patients was 68.0 ±21.5% and mean BMI was 22.35 ±4.1. The most common mycobacterial species isolated was Mycobacterium Avium Complex (47%). The mean SGRQ total score was 40.2 ±20.3 among all NTM patients. We plan to perform standard Luminex assays to identify inflammatory profiles associated with disease phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: We developed a cross sectional cohort of NTM patients including a registry of clinically relevant data for phenotyping and an accompanying biospecimen repository. Our long-term goal is to identify biomarkers indicative of disease activity and treatment response using these components.

Shifting Paradigms Regarding the Role of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis Advanced Lung Disease

Nontuberculous mycobacteria (NTM) are challenging pathogens in cystic fibrosis (CF). The best approach is unknown, in particular, in patients in need of a lung transplant (LTX). NTM sputum-positive patients were identified from all CF patients treated at the University Hospital of Zurich Adult CF Center. Course of disease and resistance to macrolide therapy was recorded. Of 6 patients who received a LTX, NTM patients were compared with patients without NTM for survival and development of chronic lung allograft dysfunction (CLAD). Of 111 CF patients, 43 (38.7%) patients grew at least one NTM culture of which 28 (25.2%) reached the stringent criteria for NTM positivity defined by three NTM positive cultures. With 32 (74.4%) isolates, M. abcessus spp. (MABSC) were the most frequent and acquired at an earlier age as compared to other NTM species (20 y [17-8] vs. 27 y [24-33]). NTM patients tended to be male and homozygous for PheF508del mutation, in particular, patients with MABSC, and more likely to require a LTX than patients without NTM (14.3% vs. 2.4%, p = 0.035). Of 28 MABSC patients with susceptibility testing, only three out of 16 (18.8%.) patients receiving treatment achieved long-term culture negativity. Treated patients were more likely to develop clarithromycin resistance than patients without treatment (68.8% vs. 16.7%, p = 0.019) with no difference in developing advanced lung disease (ALD), receiving a LTPL or death. 2 of the 6 patients undergoing LTX suffered from infection with MABSC, both of them being NTM positive before LTX. No difference in long-term survival nor in developing CLAD was observed. Two patients developed pulmonary and one extra-pulmonary infection. NTM patients are at greater risk of ALD and requiring LTX, with MABSC infection acquired at an earlier age and being more common in patients with PheF508del homozygous genotype. It is unclear whether this reflects a more rapid underlying course of CF. In MABSC patients, response to chemotherapy was poor and development of resistance common. NTM infection after LTX did not result in increased mortality or development of CLAD and BOS, but was associated with infection. Our experience supports that NTM infection should not generally be regarded as an absolute contraindication for LTX, but NTM eradication prior to LTX should be attempted.

Morbid Anatomy of Patients with Mycobacterial Infections, a Cross Sectional Autopsy Study at a Tertiary Hospital in a High Disease Burden Setting

Background: Tuberculosis is a major cause of morbidity and mortality globally. Infections caused by different mycobacteria can be clinically indistinguishable but the differences in their pathological features and mortality are unclear. Methods: To evaluate the contribution of different mycobacterial pathogens to lethal mycobacterial disease and assess subsequent pathological features, we performed autopsies of 49 patients with suspected TB. Autopsy specimens were examined histologically and cultured for mycobacteria. We identified Mycobacterium tuberculosis ( Mtb ) isolates and non-tuberculous mycobacteria (NTM), and further genotyped the Mtb isolates. Results: Mtb isolates were found in 37 patients and NTM in 12 patients. All patients had signs of caseous pneumonia and 42 patients (86%) had disease involving more than half of the lungs. Two-thirds of the patients with TB or NTM had extrapulmonary engagement in addition to pulmonary pathology. Gross pathology and histopathology were similar in TB patients and patients with NTM, except that patients with NTM had a significantly reduced tendency to cause pleural effusions. Of the Mtb isolates 55% were of the Uganda genotype, which is the predominant Mtb genotype in Uganda. This genotype was significantly more frequent in the younger patients. Conclusion: In this autopsy study of patients with presumptive TB a majority of culture positive cases were caused by Mtb. In 25% of patients NTM were identified, and histopathology was similar in TB and NTM patients, although NTM patients had significantly less pleural effusions. These results suggest that NTM contribute to mortality, and that their identification is important because of the special clinical and therapeutic implications associated with NTM infections. Funding Statement: The study was supported by funds from the Swedish International Development Cooperation Agency through Makerere University-Karolinska Institutet Research collaboration, and the Swedish Heart-Lung Foundation. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval Statement: The study was approved by the Internal Review Board (IRB) of the Makerere University School of Medicine. Final approval was granted by the Uganda National Council of Science and Technology. (HS 1364).

Socio-Economic and Environmental Factors Related to Spatial Differences in Human Non-Tuberculous Mycobacterial Diseases in the Czech Republic

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that can induce pulmonary and non-pulmonary diseases in susceptible persons. It is reported that the prevalence of NTM diseases is increasing in developed countries, but this differs by regions and countries. NTM species distribution and the rate of diseases caused by NTM vary widely in the historical territories of Moravia and Silesia (Czech Republic). This epidemiologic study of NTM diseases covers the period 2012–2018, reviews isolates obtained from patients with clinical disease and investigates correlations with related socio-economic and environmental factors. Individual NTM patients were included only once during the studied period and results were presented as incidence rate per year. The most frequently isolated NTM meeting the microbiological and clinical criteria in the study were the Mycobacterium avium-intracellulare complex, followed by Mycobacterium kansasii and Mycobacterium xenopi. A previously described endemic incidence of M. kansasii in the Karviná district and M. xenopi in the Ostrava district was also observed in this study. The incidence of NTM patients in the whole studied territory was 1.10/100,000 inhabitants (1.33/100,000 in men and 0.88/100,000 in women). The annual incidence of lymphadenitis in children (≤5 years of age) was 2.35/100,000 of the population of children during the 7 year period but increased in the year 2018 to 5.95/100,000. The rate of human tuberculosis in the studied area was 1.97/100,000 inhabitants. The incidence of NTM pulmonary diseases correlated with a lower socio-economic status (r = 0.63) and a higher concentration of benzo[a]pyrene pollution in the air (r = 0.64).

450 Esophageal Motility Disorders and GERD in Patients With Pulmonary Nontuberculous Mycobacterial Infection: A Growing Medical Problem

INTRODUCTION: The prevalence of pulmonary infections by nontuberculous mycobacteria (NTM) is increasing worldwide. The etiology of this increase is unclear. There is evidence that gastroesophageal reflux disease (GERD) is associated with NTM infections and can increase the severity of pulmonary disease. Data regarding esophageal motility in this population is sparse. We aimed to characterize esophageal motility disturbances and GERD in patients with bronchiectatic NTM and explore its associations with pulmonary pathology and lung function. METHODS: We conducted a retrospective review of all patients with a confirmed diagnosis of bronchiectatic NTM at a single center who underwent high resolution esophageal manometry (HRM) between November 2014 and March 2018. Chicago Classification 3.0 was used to characterize HRM findings. Combined multichannel intraluminal impedance-pH (pH-MII) was utilized to assess reflux burden. Statistical relationships between proportions and percentages were evaluated by Fisher’s exact test. Linear regression was utilized to assess associations with pulmonary function testing. RESULTS: A total of 32 patients underwent HRM, of which 27 underwent pH-MII. The mean age of all was 70 (SD 10), mean body mass index was 23.4 (SD 6.1), 78% were female, and 44% had a smoking history. The mean lower esophageal sphincter (LES) resting and residual pressures (mmHg) were 36.12 (SD 17.12) and 11 (SD 8.37), respectively. HRM motility disorders included 38% ineffective esophageal motility, 38% normal esophageal motility, 19% esophagogastric outflow obstruction, and 6% jackhammer esophagus. Significant evidence of GERD on pH testing was seen in 12 patients (44%). pH testing showed similar upright and supine reflux burdens of 7.6% and 7.4% respectively. On endoscopy, 2 patients (6.25%) had Barrett’s esophagus. No statistically-significant correlations were found between BMI, gender, mycobacterial organism, imaging characteristics, pulmonary function, HRM diagnosis or presence of significant reflux. CONCLUSION: Esophageal motility is frequently abnormal among patients with NTM. NTM patients also have a high prevalence of GERD, including supine GERD, and Barrett’s esophagus, which is far greater than the general population. Consideration should be given to screening for BE among patients with NTM related bronchiectasis. Larger studies are warranted to further characterize esophageal physiology in these patients and the potential impact on pulmonary pathology.