Pulmonary Nontuberculous Mycobacteria Research Articles

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.

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.

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.

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 (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. 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 twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant 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, three 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.

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.

A Case Series of Non-Tuberculous Mycobacterial Pulmonary Disease Masquerading as Malignancy From a Community-Based Hospital

Non-tuberculous mycobacteria (NTM) are ubiquitous organisms in the environment that can potentially cause a range of pulmonary and extrapulmonary infections in humans. Epidemiological risk factors and the host’s immune status determine the susceptibility to various clinical syndromes caused by different NTM species. Non-tuberculous mycobacteria pulmonary disease (NTM-PD) is primarily reported in patients with underlying lung disease. These infections often pose a significant disease burden on affected patients as they are often chronic, difficult to treat, and necessitate long-term multi-drug therapy. Mycobacterium avium complex (MAC) is the most common causative pathogen of NTM-PD in the USA, followed by Mycobacterium kansasii ( M. kansasii ). Less common species in the USA include Mycobacterium xenopi ( M. xenopi ), Mycobacterium abscessus , and others, largely depending upon the geographic location and exposure to species-specific predisposing risks. In this case series, the authors report on three elderly patients with chronic lung diseases who had pulmonary NTM disease caused by M. xenopi and MAC. The patients were encountered in both inpatient and outpatient settings from a community-based hospital in the midwestern USA. The clinical and radiological features of NTM-PD masqueraded as malignancy and posed a diagnostic dilemma. The epidemiology, clinical and radiological features, diagnosis, and management of NTM-PD are reviewed in this report. J Med Cases. 2023;14(4):141-147 doi: https://doi.org/10.14740/jmc4098

A case of Rasmussen's aneurysm caused by pulmonary nontuberculous mycobacterium.

Rasmussen's aneurysm was originally described as a rare cause of hemoptysis in tuberculosis. Dilatation of the pulmonary artery wall is caused by tuberculosis inflammation. Recently, the incidence of non-tuberculous mycobacterial (NTM) disease has increased; it now exceeds that of tuberculosis. We report a Rasmussen's aneurysm due to NTM.

Cumulative antimicrobial susceptibilities for respiratory clinical isolates of Mycobacterium avium Complex, Mycobacterium kansasii, and Mycobacterium abscessus from Pakistan 2018 to 2022.

Nontuberculous mycobacteria (NTM) are increasingly identified as causes of protracted pulmonary infections. Antibiotic susceptibility testing requires microdilution methods, which are often unavailable in laboratories in resource-poor settings. We report cumulative antibiograms for the most frequently isolated clinical pulmonary NTM from Pakistan to inform empiric antibiotic management of initial NTM infections. We analyzed data from 2018 to 2022 for the most frequently isolated and clinically relevant NTM isolated from respiratory specimens, i.e., Mycobacterium avium complex (MAC), Mycobacterium abscessus group (MAG), and Mycobacterium kansasii (MK). Antibiograms were developed using the Clinical Laboratory Standards Institute's M39ED5 standard. Percentage susceptibilities and 95% confidence intervals (CI) were calculated. Over 4 years, 529 NTM, comprising 209 MAC, 249 MAG, and 71 MK were analyzed. For MAC and MAG, where clarithromycin (CLR)-based regimens are recommended, CLR was active for 94.8% (95% CI 91.3-96.9), and 77.5% (95% CI 71.4-82.7) isolates, respectively. Combination regimens comprising 3 active drugs CLR + linezolid (LZD) + moxifloxacin for MAC and CLR + LZD + Amikacin for MAG had 98.4% (95% CI 95.9-99.4) and 68.9% (95% CI 62.3-74.8) coverage for pulmonary disease, respectively. For MK, 91.5% (95% CI 82.8-96.1) isolates were susceptible to rifampin (RIF), with a combination of RIF + CLR covering 88.7% (95% CI 79.3-94.2) of MK pulmonary infections, respectively. These data can inform empiric treatment guidance for the most common NTM pulmonary infections, i.e., for MAC, MAG, and MK disease in Pakistan.

Risk factors and outcomes of non-tuberculous mycobacteria infection in lung transplant recipients: A systematic review and meta-analysis

Patients with structural lung disease and immunocompromised status are at increased risk of pulmonary non-tuberculous mycobacteria (NTM) infection. However, literature on NTM in lung transplant recipients (LTR) is limited. We sought to systematically review the literature and perform a meta-analysis to examine associations with NTM disease and isolation in LTRs and their influence on mortality and chronic lung allograft dysfunction (CLAD). A literature search of MEDLINE and Embase was performed on February 23, 2022. NTM disease was defined according to international guidelines. Isolation was defined as any growth of NTM in culture. Odds ratios (OR) were pooled for risk factors of NTM disease or isolation, and hazard ratios (HR) were pooled for mortality or CLAD. Eleven studies totaling 3,371 patients were eligible for inclusion, 10 of which underwent meta-analysis. Cystic fibrosis (OR 1.84, 95% confidence interval [CI] 1.03-3.30; I2=0%) and pre-transplant NTM isolation (OR 2.40, 95% CI 1.20-4.83; I2=0%) were associated with NTM disease. Only male sex was associated with NTM isolation (OR 1.45, 95% CI 1.01-2.10; I2=0%). NTM disease was associated with increased mortality (HR 2.69, 95% CI 1.70-4.26; I2=0%) and CLAD (HR 2.11, 95% CI 1.03-4.35; I2=44%). NTM isolation was not associated with mortality in pooled analysis or CLAD in 1 included study. NTM disease, but not isolation, is associated with worse outcomes. Several factors were associated with development of NTM disease, including cystic fibrosis and pretransplant NTM isolation. Strategies to optimize prevention and treatment of NTM disease in lung transplant recipients are needed.

Non-tuberculous mycobacterial pulmonary disease: Awareness survey of front-desk healthcare workers in Northern Tanzania.

Over the past decade, there have been increasing reports of non-tuberculous mycobacteria (NTM) species being implicated in tuberculosis (TB) treatment failure or misdiagnosed as TB. Inadequate awareness of NTM pulmonary disease among healthcare workers (HCWs) may contribute to a low index of suspicion for patients presenting to their hospitals. In this study, we assessed the awareness of NTM pulmonary disease (NTM-PD) among front desk HCWs in Northern Tanzania. A cross-sectional descriptive survey was carried out among front desk HCWs in four administrative regions of Northern Tanzania. A standardized questionnaire was administered to consented participants from four clusters; clinicians, laboratory scientists, nurses, and pharmacists serving TB patients from Regional and District Health Facilities. Each participant was asked a set of questions, scored and the total score for each participant was determined. An awareness score was used to measure the level of awareness. The average score for all participants was estimated including the 95% confidence interval (CI). The overall awareness score was 24.1%, 95% CI 22.0-26.2%. History of training, experience in TB care, level of health facilities, age group, and setting were found to be statistically associated with the level of awareness of study participants. More than two-thirds (67%) of participants believe that pulmonary NTM and TB are clinically similar and 60% are not aware that AFB Microscopy cannot distinguish between the two. Only 13% of participants could mention at least one risk factor for NTM pulmonary disease. The level of awareness of NTM pulmonary disease was poor among HCWs in the surveyed TB clinics. National TB Programs are advised to include a topic on NTM in various on-job TB training packages for HCWs.

Clofazimine Inhalation Suspension Demonstrates Promising Toxicokinetics in Canines for Treating Pulmonary Nontuberculous Mycobacteria Infection.

Pulmonary nontuberculous mycobacteria (NTM) infection is recognized as a major global health concern due to its rising prevalence worldwide. As an opportunistic pathogen with increasing antibiotics resistance, prolonged systemic dosing with multiple antibiotics remains the primary treatment paradigm. These prolonged treatments, administered predominantly by oral or parenteral routes, often lead to systemic toxicity. A novel inhaled formulation of clofazimine may finally resolve issues of toxicity, thereby providing for improved NTM therapy. Clofazimine inhalation suspension was evaluated in canines to determine toxicity over 28 days of once-a-day dosing. The good laboratory practice (GLP) repeat dosing study evaluated low, mid, and high dosing (2.72 mg/kg and 2.95 mg/kg; 5.45 mg/kg and 5.91 mg/kg; and 10.87 mg/kg and 10.07 mg/kg, average male versus female dosing) of nebulized clofazimine over 30, 60, and 120 min using a jet nebulizer. Toxicokinetic analyses were performed on study days 29, 56, and 84. All three dose levels showed significant residual drug in lung tissue, demonstrating impressive lung loading and long lung residence. Drug concentrations in the lung remained well above the average NTM MIC at all time points, with measurable clofazimine levels at 28 and 56 days postdosing. In contrast, plasma levels of clofazimine were consistently measurable only through 14 days postdosing, with measurements below the limit of quantitation at 56 days postdosing. Clofazimine inhalation suspension may provide an effective therapy for the treatment of NTM infections through direct delivery of antibiotic to the lungs, overcoming the systemic toxicity seen in oral clofazimine treatment 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.

Diagnosis and Management of Pulmonary NTM with a Focus on Mycobacterium avium Complex and Mycobacterium abscessus: Challenges and Prospects.

Nontuberculous mycobacteria (NTM) are ubiquitous. NTM can affect different organs and may cause disseminated diseases, but the pulmonary form is the most common form. Pulmonary NTM is commonly seen in patients with underlying diseases. Pulmonary Mycobacterium avium complex (MAC) is the most common NTM disease and M. abscessus (MAB) is the most challenging to treat. This review is prepared with the following objectives: (a) to evaluate new methods available for the diagnosis of pulmonary MAC or MAB, (b) to assess advances in developing new therapeutics and their impact on treatment of pulmonary MAC or MAB, and (c) to evaluate the prospects of preventive strategies including vaccines against pulmonary MAC or MAB. A literature search was conducted using PubMed/MEDLINE and multiple search terms. The search was restricted to the English language and human studies. The database query resulted in a total of 197 publications. After the title and abstract review, 64 articles were included in this analysis. The guidelines by the American Thoracic Society (ATS), European Respiratory Society (ERS), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Infectious Diseases Society of America (IDSA) are widely applicable. The guidelines are based on expert opinion and there may be a need to broaden criteria to include those with underlying lung diseases who may not fulfill some of the criteria as 'probable cases' for better follow up and management. Some cases with only one culture-positive sputum sample or suggestive histology without a positive culture may benefit from new methods of confirming NTM infection. Amikacin liposomal inhalation suspension (ALIS), gallium containing compounds and immunotherapies will have potential in the management of pulmonary MAC and MAB. the prevalence of pulmonary NTM is increasing. The efforts to optimize diagnosis and treatment of pulmonary NTM are encouraging. There is still a need to develop new diagnostics and therapeutics.

1428. Clinical Characteristics and Management of Nontuberculous Mycobacterial Infections in the Finger Lakes Region of New York

Abstract Background Nontuberculous Mycobacteria (NTM) are ubiquitous in the environment and associated with pulmonary and extra-pulmonary infections. Evaluation and treatment of these infections is complex and prolonged, involving oral, intravenous and inhaled therapies, although not all patients with NTM need treatment. We reviewed the clinical characteristics and referral patterns of NTM patients in our institutions to evaluate resource needs. Methods We retrospectively identified all patients who had NTM isolated from 2 referral labs servicing the Finger Lakes Region of NYS, from April 1, 2018 thru March 31, 2020. Demographic, comorbidities, culture, and treatment data were collected from medical records. We compared comorbidities, clinical symptoms, and species among patients with pulmonary and extra-pulmonary NTM. Pearson’s chi-squared and student t-test were performed where appropriate for statistical analysis. Results 155 NTMs were isolated from 149 patients, 128 from pulmonary and 27 from extra-pulmonary sites. Patients with pulmonary NTM were more likely to be older, female, and have underlying lung disease (Table 1). Patients with extra-pulmonary NTM were more likely to have immunodeficiency. Mycobacterium avium complex (MAC) was isolated more frequently in pulmonary samples and rapidly growing mycobacteria more frequently from extra-pulmonary samples (Table 2). Disease site specific symptoms were more common than constitutional symptoms in both groups. 36% of patients with pulmonary NTM were treated compared with 70% of patients with extra-pulmonary NTM (Table 3). 69% were referred to Pulmonologists, and 43% to infectious diseases for evaluation and management. Table 1Demographics Demographic data for patients with pulmonary and extrapulmonary NTM Table 2Mycobacterium species Mycobacterium species isolated from patients with pulmonary and extrapulmonary NTM Table 3Clinical characteristics Clinical characteristics of patients with pulmonary and extrapulmonary NTM including symptoms, referral to specialists, whether patients were diagnosed with disease by a clinician, and how many were treated. Conclusion Though not all patients with NTM isolated from culture require treatment, most of the patients in our cohort had extensive evaluation, those on treatment required multidisciplinary care, and many not on treatment require ongoing monitoring. Knowing the volume and clinical characteristics of NTM patients in our region has helped to identify the needed resources for developing a comprehensive regional NTM center of Excellence. Other institutions can similarly assess their volume to plan for the increasing incidence of these infections. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.