Usefulness of the mini nutritional assessment short-form for evaluating nutritional status in patients with nontuberculous mycobacterial pulmonary disease: a prospective cross-sectional study.

BACKGROUND: Although the Mini Nutritional Assessment (MNA) is recognized as a useful tool for evaluating nutritional status in patients with various diseases, its applicability in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) remains undetermined. METHODS: We designed a prospective cross-sectional study to investigate whether the MNA Short-Form (MNA-SF) score can serve as a screening tool to assess the nutritional status of patients with NTM-PD. The MNA-SF was conducted upon patient enrollment, and correlation analyses were performed to compare MNA-SF scores with other nutritional measurements and disease severity. Multivariable logistic regression analyses were conducted to evaluate the association between MNA-SF scores and NTM-PD severity. RESULTS: The 194 patients with NTM-PD included in the analysis had a median age of 65.0 (59.0-69.0) years; 59.3% (n = 115) had low MNA-SF scores (< 12). The low MNA-SF group exhibited a lower body mass index (19.7 vs. 22.4 kg/m2, p < 0.001) and fat-free mass index (14.7 vs. 15.6 kg/m2, p < 0.001) than the normal MNA-SF group, as well as higher incidences of sarcopenia (20.0% vs. 6.3%, p = 0.008) and adipopenia (35.7% vs. 5.1%, p < 0.001). However, no significant differences in calorie and protein intakes were observed between the two groups. Low MNA-SF scores were associated with radiographic severity (adjusted odds ratio 2.72, 95% confidence interval 1.38-5.36) but not with forced vital capacity. CONCLUSIONS: The MNA-SF can effectively assess the nutritional status of patients with NTM-PD and can serve as an important clinical indicator in NTM-PD where treatment timing is determined by clinical judgment.

The Price of Beauty: A Literature Review on Non-Tuberculous Mycobacteria Infection After Cosmetic Procedures.

Non-tuberculous mycobacteria (NTM) infection of the skin and soft tissues is a complication of cosmetic procedures. The incidence of cutaneous NTM infections has increased significantly as aesthetic operations have become more commonplace. With the rise of cosmetic tourism, the geographic expansion of NTM infections is a major concern. Due to the unique pathogenesis of NTM infections, diagnosis and treatment remain significant challenges for clinicians. Clinical management relies on a combination of antibiotic therapy with drug susceptibility testing and appropriate surgical debridement. Some new drugs, photodynamic therapy, and bacteriophage therapy have been developed in recent years, and may improve the aesthetic outcomes. This review summarizes the cosmetic procedures prone to NTM infections in recent years and their clinical features. We propose a 2-stage treatment procedure, including a hospitalization phase and a follow-up phase. We aim to increase the alertness of clinicians to NTM infections for timely detection and treatment.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD): Epidemiology, diagnosis and multidisciplinary management.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable. This article provides an overview of NTM-PD for clinicians. We discuss how common it is, who is at risk, how it is diagnosed and the multidisciplinary approach to its clinical management.

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

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

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

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

Epidemiology and management of nontuberculous mycobacterial disease in people with cystic fibrosis, the Netherlands.

BACKGROUND: Nontuberculous mycobacteria (NTM) are opportunistic, difficult to treat pathogens. With increasing prevalence of NTM infections in people with cystic fibrosis (pwCF) and the improved life expectancy, the burden is expected to grow. METHODS: We assessed the epidemiology and management of NTM isolation and disease in pwCF in the Netherlands using a survey and retrospective, case-controlled data from the Dutch CF Registry. We determined the isolation prevalence, treatment and outcomes from 2013-2019. RESULTS: NTM isolation prevalence increased from 1.0% to 3.6% (2013-2019). This was a single NTM isolation in 53.7% of the adults and 60.0% of the children. M. abscessus and M. avium complex (MAC) were most frequent (47.1 and 30.9%). Of the treated pwCF, 48.5% attained culture conversion of M. abscessus; 54.5% for MAC. Children with an NTM isolation showed more infections with S. maltophilia and/or A. fumigatus (p < 0.001) compared to controls. In the year prior to NTM isolation, children in the NTM group had a lower mean FEV1% predicted (81.5 ± 16.7 vs. 88.6 ± 15.3, p = 0.024), while adults in the NTM group had more IV antibiotic days compared to controls (60 vs. 17, p = 0.047). In the following years, FEV1% predicted declined faster in pwCF with NTM than the control group (children: -3.8% vs. -1.6%, p = 0.023; adults: -0.7% and 0.4%, ns). CONCLUSIONS: The isolation prevalence of 3.6%, poor treatment outcomes and associated lung function decline emphasize that NTM pulmonary disease (NTM-PD) is a significant health issue among pwCF in the Netherlands. Its prevention and treatment require increased attention.

External quality assessment by European mycobacterial laboratories: results of AFB microscopy and identification rounds.

We analyzed mycobacterial stain, culture and identification EQA data from altogether 134 laboratories in 15 mainly European countries over a 4-year period. The aim was to get an overview of the performance and methods and identify diagnostic challenges. The overall success rates for staining and identification were 94% and 91%. The false negative rate for staining was significantly higher for the medium positive than the strong positive slides (11% vs 4%). The false positive rate on negative slides was 10%, indicating contamination issues. The overall success of M. tuberculosis detection was high with error rates ranging from 0.7% to 1.2%. Pre- or postanalytical errors accounted for most of the unsuccessful responses. The detection of nontuberculous mycobacteria (NTM) was less consistent; accurate species identification depended on the assays used. Only 19% of participants performed species level identification for NTMs, 47% detected the presence NTMs while 21% focused on ruling out TB.

A simple, efficient and cost-effective method for medium- to longterm maintenance and storage of Mycobacterium abscessus complex organisms.

Traditional culture of non-tuberculous mycobacteria (NTMs) has involved egg-based formulations (Lowenstein-Jensen medium, Ogawa Egg medium) or defined media (Middlebrook formulations), which have disadvatages of composition complexity, availability and cost. Previously, the commercial agar formulation, Standard Plate Count (SPC) agar [Yeast extract 2.5 g/L, pancreatic digest of casein 5.0 g/L, glucose 1.0 g/L, agar 15.0 g/L, pH 7.0 ± 0.2 at 25 °C] has been shown to be an effective solid medium for the enumeration and laboratory manipulation of Mycobacterium abscessus complex organisms. Given its relative simplicity, commercial availability and inexpensive cost, we wished to evaluate its utility for the medium- to longterm maintenance/storage of these organisms. M. abscessus complex organisms (n = 33), were inoculated onto SPCA slopes and stored undistubed in the dark at ambient temperature for six months. Following this, slopes were broken out and culture of the NTM attempted. All slopes maintained NTM culture viability and were able to initiate growth six months later. We therefore advocate the cost-effective employment of SPCA slopes for the medium- to longterm maintenance of M. abscessus organisms, without the need for complex media, availability of sterile blood and requirements for continuous -80 °C freezing.

Performance assessment of SD Bioline TB MPT64 assay for the diagnosis of Mycobacterium tuberculosis complex in Lagos, Nigeria.

This study assessed the performance of SD Bioline MPT64 immunochromatographic test for the identification of Mycobacterium tuberculosis complex (MTBC) in Nigeria.A total of 157 mycobacterial isolates, comprising 120 (76.4%) MTBC (M. tuberculosis, 112; M. africanum, 5; M. bovis, 3) and 37 (23.6%) non-tuberculous mycobacteria (NTM) isolates from patients attending six DOTS centers in Lagos between June 2012 and July 2014 were analyzed. All the isolates were grown on Bactec MGIT960 liquid media and identified in parallel by the conventional method and MPT64 immunochromatographic test. Discrepant results were resolved using the line probe assay.The comorbid disease rates for HIV and type 2 diabetes were 20.9% and 8.2%, respectively. Compared to the conventional method, SD Bioline MPT64 identified 117 MTBC isolates correctly, producing a sensitivity of 97.5% (95% CI, 92.9-99.2) at a shorter growing median time of 11 days compared to 26 days by the conventional method. The three undetected MTBC were confirmed by the line probe assay to be M. tuberculosis strains. The test also identified all the NTM correctly producing a specificity of 100% (95% CI, 90.7-100).This study supports the integration of SD Bioline TB MPT64 antigen test into diagnostic workflow for rapid MTBC case identification in Nigeria.

Validity of Diagnosis Code-Based Claims to Identify Pulmonary NTM Disease in Bronchiectasis Patients.

Nontuberculous mycobacteria infection is increasing in incidence and can lead to chronic, debilitating pulmonary disease. We investigated the accuracy of diagnosis code-based nontuberculous mycobacteria lung disease claims among Medicare beneficiaries in the United States. We observed that these claims have moderate validity, but given their low sensitivity, incidence might be underestimated.

Predictive modeling of nontuberculous mycobacterial pulmonary disease epidemiology using German health claims data.

OBJECTIVES: Administrative claims data are prone to underestimate the burden of non-tuberculous mycobacterial pulmonary disease (NTM-PD). METHODS: We developed machine learning-based algorithms using historical claims data from cases with NTM-PD to predict patients with a high probability of having previously undiagnosed NTM-PD and to assess actual prevalence and incidence. Adults with incident NTM-PD were classified from a representative 5% sample of the German population covered by statutory health insurance during 2011-2016 by the International Classification of Diseases, 10th revision code A31.0. Pre-diagnosis characteristics (patient demographics, comorbidities, diagnostic and therapeutic procedures, and medications) were extracted and compared to that of a control group without NTM-PD to identify risk factors. RESULTS: Applying a random forest model (area under the curve 0.847; total error 19.4%) and a risk threshold of >99%, prevalence and incidence rates in 2016 increased 5-fold and 9-fold to 19 and 15 cases/100,000 population, respectively, for both coded and non-coded vs. coded cases alone. CONCLUSIONS: The use of a machine learning-based algorithm applied to German statutory health insurance claims data predicted a considerable number of previously unreported NTM-PD cases with high probabilty.

Hospital ice, ice machines, and water as sources of nontuberculous mycobacteria: Description of qualitative risk assessment models to determine host-Nontuberculous mycobacteria interplay.

Over the last 30 years, there have been at least 17 published reports of nontuberculous mycobacteria (NTMs) being isolated from hospital ice or ice-making machines. Of these, 12 were reports of pseudo-outbreaks, i.e., the nosocomial transmission of organism from hospital ice/ice machines to patients, resulting in patient colonization, but with no disease manifestations. In addition, there were five outbreaks that resulted in clinical disease/pathology associated with NTM organism. Eleven different species of NTMs have been associated with these reports, where over half (59%) of the species identified were Mycobacterium fortuitum (18%), Mycobacterium gordonae (14%), Mycobacterium mucogenicum (14%), and Mycobacterium porcinum (14%). Several of these reports clearly documented that ice machines had been properly maintained, cleaned, and serviced in accordance with the CDC guidelines yet became contaminated with NTM organisms. These reports frequently detail that after extensive cleaning/disinfection following the discovery of NTM organisms, ice machines remained contaminated with NTM organisms, highlighting the difficulty in eradicating these from ice machines, once contaminated. Several reports identified that the only remedy to the contamination problem was to replace the ice machine with a new machine. Two qualitative risk assessment models are presented for (i) patients exposed to contaminated ice machine but before NTM colonization/infection and (ii) patients already colonized with NTMs from ice machines. Therefore, to protect immunocompromised/immunosuppressed patients' safety, especially during surgical or respiratory procedures, ice should not be sourced from the ice machine but should be made from sterile water and stored safely and separately away from the ice machine.

Assessment of Soil Features on the Growth of Environmental Nontuberculous Mycobacterial Isolates from Hawai'i.

Environmental nontuberculous mycobacteria (NTM), with the potential to cause opportunistic lung infections, can reside in soil. This might be particularly relevant in Hawai'i, a geographic hot spot for NTM infections and whose soil composition differs from many other areas of the world. Soil components are likely to contribute to NTM prevalence in certain niches as food sources or attachment scaffolds, but the particular types of soils, clays, and minerals that impact NTM growth are not well-defined. Hawai'i soil and chemically weathered rock (saprolite) samples were examined to characterize the microbiome and quantify 11 mineralogical features as well as soil pH. Machine learning methods were applied to identify important soil features influencing the presence of NTM. Next, these features were directly tested in vitro by incubating synthetic clays and minerals in the presence of Mycobacteroides abscessus and Mycobacterium chimaera isolates recovered from the Hawai'i environment, and changes in bacterial growth were determined. Of the components examined, synthetic gibbsite, a mineral form of aluminum hydroxide, inhibited the growth of both M. abscessus and M. chimaera, while other minerals tested showed differential effects on each species. For example, M. abscessus (but not M. chimaera) growth was significantly higher in the presence of hematite, an iron oxide mineral. In contrast, M. chimaera (but not M. abscessus) counts were significantly reduced in the presence of birnessite, a manganese-containing mineral. These studies shed new light on the mineralogic features that promote or inhibit the presence of Hawai'i NTM in Hawai'i soil.IMPORTANCE Globally and in the United States, the prevalence of NTM pulmonary disease-a potentially life-threatening but underdiagnosed chronic illness-is prominently rising. While NTM are ubiquitous in the environment, including in soil, the specific soil components that promote or inhibit NTM growth have not been elucidated. We hypothesized that NTM culture-positive soil contains minerals that promote NTM growth in vitro Because Hawai'i is a hot spot for NTM and a unique geographic archipelago, we examined the composition of Hawai'i soil and identified individual clay, iron, and manganese minerals associated with NTM. Next, individual components were evaluated for their ability to directly modulate NTM growth in culture. In general, gibbsite and some manganese oxides were shown to decrease NTM, whereas iron-containing minerals were associated with higher NTM counts. These data provide new information to guide future analyses of soil-associated factors impacting persistence of these soil bacteria.

Costs Associated with Nontuberculous Mycobacteria Infection, Ontario, Canada, 2001-2012.

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001-2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.

Assessment of current diagnostic algorithm for detection of mixed infection with Mycobacterium tuberculosis and nontuberculous mycobacteria.

BACKGROUND: The increasing pulmonary diseases are reported to be affected by mixed infection of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM). In this study, our objective was to assess the efficiency of mycobacterial culture plus DNA sequencing to detect the mixed infections with MTB and various NTM organisms. We also aimed to investigate how efficiently GeneXpert detected MTB in mixed infections with NTM in in vitro models. METHODS: A serial of mixed infection samples was generated by combining suspensions of MTB and five NTM bacteria, respectively. The mixed suspensions were further detected with GeneXpert and liquid culture plus DNA sequencing. RESULTS: Overall, the GeneXpert assay exhibited promising capability to identify the presence of MTB at different proportions ranging from 1% to 99%. For the liquid culture, the subsequent DNA sequencing only detected the presence of NTM bacteria in the mixed samples, which the proportion of NTM ranged from 1% to 99%, including M. intracellulare, M. kansasii, M. abscessus, and M. fortuitum. For M. avium, DNA sequencing was able to identify the mixtures as M. avium infection in suspensions with no less than 10% M. avium bacteria, whereas only MTB was found in the other suspensions with less M. avium bacteria. CONCLUSIONS: Our data demonstrate that the current diagnostic algorithm cannot yield a precise detection of mixed infections with MTB and NTM bacteria. The GeneXpert assay only identify MTB in the mixed samples, while the subculture plus DNA sequencing prefers to identify the NTM species with the higher growth rate. Further targeted molecular analysis by specific capture of multiple loci of mycobacterial species from specimens is urgently required to solve this diagnostic dilemma.

What are the challenges in commercial non-tuberculous mycobacteria (NTM) drug discovery and how should we move forward?

Introduction: Despite the great clinical need, the development of drugs for treating non-tuberculous mycobacteria lung disease (NTM-LD), partly from the scientific difficulty, but also because the eventual size and types of markets for commercially-developed drugs has been unclear.Areas Covered: Here, key questions regarding the markets for commercial NTM-LD drugs are discussed, together with potential solutions for resolving these questions.Expert Opinion: Many of these questions will become better resoled over time, but uncertainties will remain around likely competition and whether approval and reimbursement will be achieved for all NTM-LD or smaller subsections of the market. Additionally, both 'push' and 'pull' incentives should be considered by policymakers to ensure the NTM-LD market is successfully addressed.