Mycobacterium Research Articles

Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment

BackgroundClofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD. MethodsThis prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included. ResultsThe steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study. ConclusionCFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease

ABSTRACT The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

Differential radiological features of patients infected or colonised with slow-growing non-tuberculous mycobacteria

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl − 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy.

The Presence of esat-6 and cfp10 and Other Gene Orthologs of the RD 1 Region in Non-Tuberculous Mycobacteria, Mycolicibacteria, Mycobacteroides and Mycolicibacter as Possible Impediments for the Diagnosis of (Animal) Tuberculosis.

The Esx-1 family proteins of the Type VII secretion systems of Mycobacterium bovis and Mycobacterium tuberculosis have been assessed and are frequently used as candidates for tuberculosis (TB) diagnosis in both humans and animals. The presence of ESAT-6 and CFP 10 proteins, which are the most immunogenic proteins of the Esx-1 system and have been widely investigated for the immunodiagnosis of tuberculosis, in some Mycobacteriaceae and in Mycobacterium leprae, poses limitations for their use in specific diagnoses of TB. As such, to improve the specificity of the ESAT-6/CFP 10-based cell-mediated immunity (CMI) assays, other proteins encoded by genes within and outside the RD 1 region of the esx-1 locus have been evaluated as candidate antigens for CMI, as well as to investigate humoral responses in combination with ESAT-6 and or CFP 10, with varying specificity and sensitivity results. Hence, in this study, we evaluated various non-tuberculous mycobacteria (NTM), Mycolicibacterium, Mycolicibacter and Mycobacteroides species genomes available on the NCBI database for the presence and composition of the RD1 region of the esx-1 locus. In addition, we also assayed by polymerase chain reaction (PCR) and sequencing of Mycobacteriaceae available in our culture collection for the presence and sequence diversity of esxA and esxB genes encoding ESAT-6 and CFP 10, respectively. Whole genome sequence (WGS) data analysis revealed the presence of RD 1 gene orthologs in 70 of the over 100 published genomes of pathogenic and non- pathogenic Mycobcteriaceae other than tuberculosis. Among species evaluated from our culture collection, in addition to earlier reports of the presence of esxA and esxB in certain Mycolicibacterium, Mycolicibacterium septicum/peregrinum, Mycolicibacterium porcinum and Mycobacterium sp. N845T were also found to harbour orthologs of both genes. Orthologs of esxA only were detected in Mycobacterium brasiliensis, Mycolicibacterium elephantis and Mycolicibacterium flouroantheinivorans, whereas in Mycolicibacter engbackii, Mycolicibacterium mageritense and Mycobacterium paraffinicum, only esxB orthologs were detected. A phylogenetic analysis based on esxA and esxB sequences separated slow-growing from rapidly growing bacteria. These findings strengthen previous suggestions that esxA and esxB may be encoded in the majority of Mycobacteriaceae. The role of the Esx-1 system in both pathogenic and non-pathogenic Mycobacteriaceae needs further investigation, as these species may pose limitations to immunological assays for TB.

CT informs detection and treatment options in rheumatoid arthritis complicated by pulmonary non-tuberculous mycobacterial disease from the FIRST registry

ObjectiveTo investigate the early detection of pulmonary non-tuberculous mycobacterial (PNTM) disease by CT before the initiation of molecular-targeted therapeutic drugs in patients with rheumatoid arthritis (RA) and the efficacy and...

Design, Synthesis and In vitro Screening of Novel 2-Mercaptobenzothiazole- Clubbed Phenylacetamides as Potential Antibacterial Agents

Background: The frightening rise of bacterial resistance is occurring worldwide and endangering the efficacy of antibiotics. Hence, the development of novel and potent antibacterial is a need of the day. Objective: In this study, we designed and synthesized compounds C1-C11. These compounds are characterized by their FT-IR, NMR and MS spectral data and examined in vitro for their antibacterial activity. Methods: Compounds C1-C11 were synthesized by reacting 2-mercaptobenzothiazole with appropriate chloroacetamide in the presence of anhydrous potassium carbonate and dry acetone at room temperature. To assess the antibacterial activity, minimum inhibitory and minimum bactericidal concentrations were examined by broth microdilution method against the selected strains of both Gram-positive and Gramnegative bacteria. Time-kill kinetics study was also performed as per CLSI guidelines. Results: Compounds C6 and C7 displayed promising activity against Staphylococcus aureus ATCC 43300 with MICs of 9.43 and 7.73 μM, respectively. These two compounds also displayed promising antibacterial activity against S. aureus 5021 with MIC values of 7.53 and 9.68 μM, respectively. In MBC determination, these two compounds (tested in the concentration range of 7.53 to 262.3 μM) displayed bactericidal activity against methicillin resistant S. aureus ATCC 43300, S. aureus NCIM 5021 and S. aureus NCIM 5022. In time-kill kinetics study, compounds C6 and C7 also exhibited bactericidal activity against S. aureus NCIM 5021 and S. aureus ATCC 43300 after 12 h of exposure. In general, all tested compounds exhibited poor activity against Mycobacterium sp. NCIM 2984 and also against tested Gramnegative bacteria Klebsiella pneumoniae NCIM 2706, Escherichia coli NCIM 2065 and Pseudomonas aeruginosa NCIM 2036. Further, computed ADMET properties of C1-C11 showed a favourable pharmacokinetic profile with zero violation of Lipinski’s rule of five. Conclusion: The result showed that in phenylacetamides C6 and C7 presence of phenyl ring substituted with -CF3 group is responsible for their high antibacterial activity against S. aureus ATCC 43300 (MICs, 9.43 and 7.73 μM, respectively). These two compounds also exhibited bactericidal activity respectively against S. aureus NCIM 5021 in time kill kinetics study.

Evaluation of a national multidisciplinary meeting for non-tuberculous mycobacterial disease.

Evaluation of a national multidisciplinary meeting for non-tuberculous mycobacterial disease.

Comparison of efficacies of different treatments for nontuberculous mycobacterial pulmonary disease in Anhui Province, China.

Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui. Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens. Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found. In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.

Nontuberculous mycobacterial disease in children: A systematic review and meta-analysis

BackgroundThe prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly different from those of adult patients, but the knowledge of the disease is generally poor. MethodsEnglish databases (PubMed, Web of Science, Embase, BIOSIS) and Chinese databases (CNKI, Wanfan, VIP) were searched on October 15th, 2022. All the articles of cross-sectional and cohort studies reporting the species composition and lesion site of the NTM disease in children using well-recognized NTM species identification methods were taken into account. Using a random effects model, we assessed the disease lesion sites and the prevalence of different NTM species in pediatric NTM disease. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. ResultsThe prevalence rates of NTM disease in children ranged between 0.6 and 5.36/100,000 in different countries, and Europe reported the highest prevalence rate. The most common clinical lesion site was lymph node, accounting for 71.1 % (55.0 %–83.2 %), followed by lung (19.3 %, 9.8%–34.4 %）and then skin and soft tissue (16.6 %,13.5%–20.3 %). Mycobacterium avium complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%–69.6 %). Inconsistent with adult patients, Mycobacterium avium accounted for a dominant proportion in MAC than Mycobacterium intracellulare. ConclusionsThe lymph node was the most affected organ in pediatric NTM disease, while Mycobacterium avium was the most isolated pathogenic species in children.

Comparison of the sputum microbiome between patients with stable nontuberculous mycobacterial pulmonary disease and patients requiring treatment.

We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.

Amikacin Liposome Inhalation Suspension (ALIS) as part of the initial regimen in the treatment of non-tuberculous mycobacteria (NTM) treatment

Managing non-tuberculous mycobacterial (NTM) lung disease poses challenges due to the extended treatment duration and frequent occurrence of adverse effects. Amikacin Liposome Inhalation Suspension (ALIS) is a liposomal form of amikacin, delivered through inhalation directly to the lungs. Recently published guidelines now recommend the use of (ALIS) as a component of the treatment regimen for Mycobacterium avium complex (MAC) lung disease in cases of refractory disease. However, no data exist supporting its inclusion in the initial regimen. In this case report, we present a patient with a newly diagnosed M. intracellulare infection and extensive bilateral disease who received ALIS due to the precarious use of parenteral amikacin. A 64-year-old female patient, with impaired kidney function due to kidney cancer and nephrectomy presented with cough and malaise over the last three months. The CT scan performed demonstrated multiple bilateral nodules and infiltrates, as well as bronchiectasis. A bronchoscopy was conducted and M.intracellulare was isolated from the bronchoalveolar lavage. Given the extensive nature of the disease, even in the absence of a cavity and given the impaired kidney function, the patient was administered a therapy regimen including azithromycin, rifampicin, ethambutol, and ALIS. The patient benefited the most of the treatment in terms of clinical, microbiological and imaging aspects while avoiding serious adverse effects due to amikacin. It is necessary to always consider the best treatment for the patient even beyond established guidelines in order to achieve the best outcome. ALIS is a promising new treatment that needs to be studied further.

From Antagonism to Enhancement: Triton X-100 Surfactant Affects Phenanthrene Interfacial Biodegradation by Mycobacteria through a Shift in Uptake Mechanisms.

Polycyclic aromatic hydrocarbons (PAHs), as persistent environmental pollutants, often reside in nonaqueous-phase liquids (NAPLs). Mycobacterium sp. WY10, boasting highly hydrophobic surfaces, can adsorb to the oil-water interface, stabilizing the Pickering emulsion and directly accessing PAHs for biodegradation. We investigated the impact of Triton X-100 (TX100) on this interfacial uptake of phenanthrene (PHE) by Mycobacteria, using n-tetradecane (TET) and bis-(2-ethylhexyl) phthalate (DEHP) as NAPLs. Interfacial tension, phase behavior, and emulsion stability studies, alongside confocal laser scanning microscopy and electron microscope observations, unveiled the intricate interplay. In surfactant-free systems, Mycobacteria formed stable W/O Pickering emulsions, directly degrading PHE within the NAPLs because of their intimate contact. Introducing low-dose TX100 disrupted this relationship. Preferentially binding to the cells, the surfactant drastically increased the cell hydrophobicity, triggering desorption from the interface and phase separation. Consequently, PAH degradation plummeted due to hindered NAPL access. Higher TX100 concentrations flipped the script, creating surfactant-stabilized O/W emulsions devoid of interfacial cells. Surprisingly, PAH degradation remained efficient. This paradox can be attributed to NAPL emulsification, driven by the surfactant, which enhanced mass transfer and brought the substrate closer to the cells, despite their absence at the interface. This study sheds light on the complex effect of surfactants on Mycobacteria and PAH uptake, revealing an antagonistic effect at low concentrations that ultimately leads to enhanced degradation through emulsification at higher doses. These findings offer valuable insights into optimizing bioremediation strategies in PAH-contaminated environments.

Heterotrophic bacteria isolated from a chloraminated system accelerate chloramine decay

This work comprehensively demonstrates the ability of heterotrophic bacteria, isolated from a chloraminated system, to decay chloramine. This study non-selectively isolated 62 cultures of heterotrophic bacteria from a water sample (0.002 mg-N/L nitrite and 1.42 mg/L total chlorine) collected from a laboratory-scale reactor system; most of the isolates (93.3%) were Mycobacterium sp. Three species of Mycobacterium and one species of Micrococcus were inoculated to a basal inorganic medium with initial concentrations of acetate (from 0 to 24 mg-C/L) and 1.5 mg/L chloramine. Bacterial growth coincided with declines in the concentrations of chloramine, acetate, and ammonium. Detailed experiments with one of the Mycobacterium sp. isolates suggest that the common mechanism of chloramine loss is auto-decomposition likely mediated by chloramine-decaying proteins. The ability of the isolates to grow and decay chloramine underscores the important role of heterotrophic bacteria in the stability of chloramine in water-distribution systems. Existing strategies based on controlling nitrification should be augmented to include minimizing heterotrophic bacteria.

Observational and cross-sectional study on clinical profile of nontuberculous mycobacterial (NTM) disease in patients at tertiary care hospital of central India

Background Nontuberculous Mycobacterial (NTM) diseases present unique clinical challenges and are increasingly recognised as significant contributors to respiratory and extrapulmonary morbidity. This study protocol outlines an observational and cross-sectional investigation aiming to comprehensively understand the clinical profile of NTM disease, including its prevalence, risk factors, and clinical features, in patients at a tertiary care hospital in central India. Methods Over two years, from July 2022 to June 2024, a convenience sample size will be recruited from TB suspects meeting inclusion criteria. Comprehensive data collection will be conducted, including demographic information, clinical history, radiological findings, microbiological test results, and risk factor assessments. Statistical methods will be applied to the collected data, including descriptive statistics, comparative analysis, risk factor assessments, and multivariate analyses. Expected Results The study aims to provide valuable insights into the prevalence and clinical manifestations of NTM disease, shedding light on the risk factors contributing to its occurrence. The statistical analyses will identify key factors associated with NTM disease and characterise its clinical and radiological features.

Sputum bacterial microbiota signature as a surrogate for predicting disease progression of nontuberculous mycobacterial lung disease

ObjectivesPredicting progression of nontuberculous mycobacterial lung disease (NTM-LD) remains challenging. This study evaluated whether sputum bacterial microbiome diversity can be the biomarker and provide novel insights into related phenotypes and treatment timing. MethodsWe analyzed 126 sputum microbiomes of 126 patients with newly diagnosed NTM-LD due to Mycobacterium avium complex, M. abscessus complex, and M. kansasii between May 2020 and December 2021. Patients were followed for 2 years to determine their disease progression status. We identified consistently representative genera that differentiated the progressor and nonprogressor by using six methodologies. These genera were used to construct a prediction model using random forest with 5-fold cross validation. ResultsDisease progression occurred in 49 (38.6%) patients. Compared with nonprogressors, α-diversity was lower in the progressors. Significant compositional differences existed in the β-diversity between groups (p=0.001). The prediction model for NTM-LD progression constructed using seven genera (Burkholderia, Pseudomonas, Sphingomonas, Candidatus Saccharibacteria, Phocaeicola, Pelomonas, and Phascolarctobacterium) with significantly differential abundance achieved an area under curve of 0.871. ConclusionsIdentification of the composition of sputum bacterial microbiome facilitates prediction of the course of NTM-LD, and maybe used to develop precision treatment involving modulating the respiratory microbiome composition to ameliorate NTM-LD.

Exploring the Association of Bacterial Coinfections with Clinical Characteristics of Patients with Nontuberculous Mycobacterial Pulmonary Disease.

Clinical data for bacterial coinfection of the lower respiratory tract in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are scarce. This study aims to assess the prevalence of bacterial coinfection and clinical features in NTM-PD patients. This retrospective study screened 248 patients with NTM-PD who underwent bronchoscopy between July 2020 and July 2022, from whom newly diagnosed NTM-PD patients were analyzed. Bacterial culture using bronchial washing fluid was performed at the time of NTM-PD diagnosis. In the 180 patients (median age 65 years; 68% female), Mycobacterium avium complex (86%) was the most frequent NTM isolated. Bacterial coinfections were detected in 80 (44%) patients. Among them, the most common bacterium was Klebsiella pneumoniae (n=25/80, 31.3%), followed by Pseudomonas aeruginosa (n=20/80, 25%) and Staphylococcus aureus (n=20/80, 25%). Compared with NTM-PD patients without bacterial coinfections, patients with bacterial coinfections showed more frequent extensive lung involvement (33% vs. 1%, p&lt;0.001). Additionally, compared with NTM-PD patients without P. aeruginosa infection, those with P. aeruginosa infection were older (74 years vs. 64 years, p=0.001), had more frequent respiratory symptoms (cough/excessive mucus production 70% vs. 38%, p=0.008; dyspnea 30% vs. 13%, p=0.047), and had extensive lung involvement (60% vs. 9%, p&lt;0.001). Less than half of patients with newly diagnosed NTM-PD had bacterial coinfections, linked to extensive lung involvement. Specifically, P. aeruginosa coinfection was significantly associated with older age, more frequent respiratory symptoms, and extensive lung involvement.

The diagnostic impact of fractional exhaled nitric oxide for asthmatic cough in nontuberculous mycobacterial pulmonary disease.

Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM.

Nonpharmacological Treatment for Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) results from the exposure of susceptible hosts to a diverse group of environmental mycobacteria. The emphasis on nonpharmacological strategies is motivated by the widespread presence of NTM in various environments, and the inconsistent success rates of pharmacological treatments. Modifiable factors contributing to NTM-PD development include impaired airway clearance, low body mass index, gastroesophageal reflux disease, and exposure to NTM habitats. This suggests that lifestyle and environmental modifications could affect disease development and progression. The review highlights several modalities that can modify the risk factors. Airway clearance techniques, informed by the "gel-on-brush" model of the bronchial epithelium, aim to enhance mucociliary clearance, and have the potential to alleviate symptoms and improve lung function. The impact of nutritional status is also examined, with a lower body mass index linked to an increased risk and progression of NTM-PD, indicating the importance of targeted nutritional support. Additionally, the theoretical and epidemiological links between gastroesophageal reflux disease and NTM-PD advocate careful management of reflux episodes. Understanding the risk of NTM transmission through environmental exposure to contaminated water and soil is also crucial. Strategies to mitigate this risk, including effective water management and minimizing soil contact, are presented as vital preventive measures. The review supports the inclusion of nonpharmacological treatments within a comprehensive NTM-PD management strategy, alongside conventional pharmacological therapies. This integrated approach seeks to improve the overall understanding and handling of NTM-PD.

Time to diagnosis of nontuberculous mycobacterial pulmonary disease and longitudinal changes on CT before diagnosis

BackgroundThe healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis. Patients and methodsWe retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system. ResultsThe median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis. ConclusionThe diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.

Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. A favourable response to treatment was seen in 74% of patients with a high relapse rate.