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RMD Open Jun 2024To investigate the early detection of pulmonary non-tuberculous mycobacterial (PNTM) disease by CT before the initiation of molecular-targeted therapeutic drugs in...
OBJECTIVE
To 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 safety of combined treatment with antibiotics.
METHODS
Patients with RA underwent chest CT before the introduction of molecular-targeted therapies in the Further Improvement of Rheumatoid arthritis Treatment registry. The primary endpoint was the number of patients who were detected by CT as having PNTM disease, complicating RA.
RESULTS
Of 4447 patients with RA who underwent chest CT, 107 had suspected PNTM disease, and 33 diagnoses were confirmed by culture. In 14 of the 33 patients, plain radiographs showed no abnormalities; PNTM disease was only observed on CT scans. The prevalence of PNTM disease in patients with RA requiring molecular-targeted treatment was six times higher than that in healthy individuals. 31 patients initiated molecular-targeted therapeutic drugs in combination with anti-NTM treatment, and 28 were followed up for 24 months. No significant difference was observed in the retention rate and RA disease activity at 24 months between the PNTM and non-PNTM groups. Coexisting PNTM disease did not affect treatment discontinuation. None of the 28 patients in the PNTM group experienced exacerbation of PNTM disease.
CONCLUSION
CT screening before the initiation of molecular-targeted treatment enabled the detection of asymptomatic PNTM that was undetectable on plain radiographs. This study showed that molecular-targeted therapeutic drugs in combination with anti-NTM treatment could control the disease activity of both PNTM and RA.
Topics: Humans; Arthritis, Rheumatoid; Female; Male; Tomography, X-Ray Computed; Registries; Mycobacterium Infections, Nontuberculous; Middle Aged; Aged; Nontuberculous Mycobacteria; Anti-Bacterial Agents; Treatment Outcome; Adult; Molecular Targeted Therapy
PubMed: 38866590
DOI: 10.1136/rmdopen-2023-004049 -
Journal of Infection in Developing... May 2024Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic... (Comparative Study)
Comparative Study
INTRODUCTION
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.
METHODOLOGY
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; China; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Male; Female; Middle Aged; Aged; Anti-Bacterial Agents; Treatment Outcome; Nontuberculous Mycobacteria; Adult; Microbial Sensitivity Tests; Lung Diseases; Sputum
PubMed: 38865399
DOI: 10.3855/jidc.18604 -
Journal of Infection in Developing... May 2024Mycobacterium canariasense is a relatively rare and rapidly growing nontuberculous mycobacterium (NTM) infection.
INTRODUCTION
Mycobacterium canariasense is a relatively rare and rapidly growing nontuberculous mycobacterium (NTM) infection.
CASE REPORT
This case report describes a 36-year-old man with a Canariasense infection in the lung with solitary cavitation nodules located subpleural on CT scan, for which the final diagnosis was made by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF-mNGS). It was successfully treated with levofloxacin and amikacin.
CONCLUSIONS
This experience is instructive because clinical diagnostic and CT imaging characteristics and treatment strategy guidelines for pulmonary infections caused by M. canariasense have not yet been established.
Topics: Humans; Male; Adult; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; Tomography, X-Ray Computed; Bronchoalveolar Lavage Fluid; Lung; Levofloxacin; Amikacin; Nontuberculous Mycobacteria; High-Throughput Nucleotide Sequencing; Treatment Outcome
PubMed: 38865393
DOI: 10.3855/jidc.18535 -
Microbiology Spectrum Jul 2024Iron scavenging is required for full virulence of mycobacterial pathogens. During infection, the host immune response restricts mycobacterial access to iron, which is...
Iron scavenging is required for full virulence of mycobacterial pathogens. During infection, the host immune response restricts mycobacterial access to iron, which is essential for bacterial respiration and DNA synthesis. The iron-dependent regulator (IdeR) responds to changes in iron accessibility by repressing iron-uptake genes when iron is available. In contrast, iron-uptake gene transcription is induced when iron is depleted. The gene is essential in and is required for bacterial growth. To further study how iron regulates transcription, wee developed an iron responsive reporter system that relies on an IdeR-regulated promoter to drive Cre and mediated recombination in . Recombination leads to the expression of an antibiotic resistance gene so that mutations that activate the IdeR-regulated promoter can be selected. A transposon library in the background of this reporter system was exposed to media containing iron and hemin, and this resulted in the selection of mutants in the antioxidant mycothiol synthesis pathway. We validated that inactivation of the mycothiol synthesis gene results in increased recombination and increased IdeR-regulated promoter activity in the reporter system. Further, we show that vitamin C, which has been shown to oxidize iron through the Fenton reaction, can decrease promoter activity in the mutant. We conclude that the intracellular redox state balanced by mycothiol can alter IdeR activity in the presence of iron.IMPORTANCE is a tractable organism to study mycobacterial gene regulation. We used to construct a novel recombination-based reporter system that allows for the selection of mutations that deregulate a promoter of interest. Transposon mutagenesis and insertion sequencing (TnSeq) in the recombination reporter strain identified genes that impact iron regulated promoter activity in mycobacteria. We found that the mycothiol synthesis gene is required for IdeR mediated transcriptional regulation by maintaining intracellular redox balance. By affecting the oxidative state of the intracellular environment, mycothiol can modulate iron-dependent transcriptional activity. Taken more broadly, this novel reporter system can be used in combination with transposon mutagenesis to identify genes that are required by to overcome temporary or local changes in iron availability during infection.
Topics: Iron; Mycobacterium smegmatis; Oxidation-Reduction; Gene Expression Regulation, Bacterial; Bacterial Proteins; Inositol; Genes, Reporter; Glycopeptides; Promoter Regions, Genetic; Cysteine; Mycobacterium tuberculosis; DNA Transposable Elements; Repressor Proteins
PubMed: 38860795
DOI: 10.1128/spectrum.00487-24 -
Gut Microbes 2024The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota...
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 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 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 or its capsular polysaccharides might help prevent NTM-LD.
Topics: Dysbiosis; Gastrointestinal Microbiome; Animals; Toll-Like Receptor 2; Humans; Mice; Male; Female; Mycobacterium Infections, Nontuberculous; Middle Aged; Feces; Aged; Prevotella; Lung Diseases; Nontuberculous Mycobacteria; Disease Susceptibility; Mice, Inbred C57BL; Lung
PubMed: 38860456
DOI: 10.1080/19490976.2024.2361490 -
Scientific Reports Jun 2024Non-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...
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.
Topics: Humans; Male; Female; Mycobacterium Infections, Nontuberculous; Tomography, X-Ray Computed; Aged; Middle Aged; Nontuberculous Mycobacteria; Mycobacterium avium Complex; Lung; Retrospective Studies; Adult; Mycobacterium avium-intracellulare Infection
PubMed: 38858499
DOI: 10.1038/s41598-024-64029-0 -
Canadian Journal of Microbiology Jul 2024Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available....
Non-tuberculosis infections in immunocompromised patients represent a cause for concern, given the increased risks of infection, and limited treatments available. Herein, we report that molecules for binding to the catalytic site of histone deacetylase (HDAC) inhibit its activity, thus increasing the innate immune response against environmental mycobacteria. The action of HDAC inhibitors (iHDACs) was explored in a model of type II pneumocytes and macrophages infection by . The results show that the use of 1,3-diphenylurea increases the expression of the TLR-4 in infected MDMs, as well as the production of defb4, IL-1β, IL-12, and IL-6. Moreover, we observed that aminoacetanilide upregulates the expression of TLR-4 together with TLR-9, defb4, CAMP, RNase 6, RNase 7, IL-1β, IL-12, and IL-6 in T2P. Results conclude that the tested iHDACs selectively modulate the expression of cytokines and antimicrobial peptides that are associated with reduction of non-tuberculous mycobacteria infection.
Topics: Immunity, Innate; Humans; Mycobacterium Infections, Nontuberculous; Histone Deacetylase Inhibitors; Cytokines; Drug Repositioning; Macrophages; Nontuberculous Mycobacteria; Mycobacterium
PubMed: 38855942
DOI: 10.1139/cjm-2023-0127 -
Frontiers in Cellular and Infection... 2024() is an opportunistic pathogen afflicting individuals with underlying lung disease such as Cystic Fibrosis (CF) or immunodeficiencies. Current treatment strategies for...
() is an opportunistic pathogen afflicting individuals with underlying lung disease such as Cystic Fibrosis (CF) or immunodeficiencies. Current treatment strategies for infections are limited by its inherent antibiotic resistance and limited drug access to in its niches resulting in poor cure rates of 30-50%. ability to survive within macrophages, granulomas and the mucus laden airways of the CF lung requires adaptation via transcriptional remodeling to counteract stresses like hypoxia, increased levels of nitrate, nitrite, and reactive nitrogen intermediates. () is known to coordinate hypoxic adaptation via induction of respiratory nitrate assimilation through the nitrate reductase . , on the other hand, does not encode a respiratory nitrate reductase. In addition, our recent study of the transcriptional responses of to hypoxia revealed marked down-regulation of a locus containing putative nitrate assimilation genes, including the orphan response regulator (nitrate/nitrite assimilation regulator). These putative nitrate assimilation genes, (nitrate/nitrite transporter), (nitrite reductase), , and (ferrochelatase) are arranged contiguously while (assimilatory nitrate reductase identified in this work) is encoded in a different locus. Absence of a respiratory nitrate reductase in and down-regulation of nitrogen metabolism genes in hypoxia suggest interplay between hypoxia adaptation and nitrate assimilation are distinct from what was previously documented in . The mechanisms used by to fine-tune the transcriptional regulation of nitrogen metabolism in the context of stresses e.g. hypoxia, particularly the role of NnaR, remain poorly understood. To evaluate the role of NnaR in nitrate metabolism we constructed a knockout strain ( ) and complement ( ) to investigate transcriptional regulation and phenotypes. qRT-PCR revealed NnaR is necessary for regulating nitrate and nitrite reductases along with a putative nitrate transporter. Loss of NnaR compromised the ability of to assimilate nitrate or nitrite as sole nitrogen sources highlighting its necessity. This work provides the first insights into the role of NnaR setting a foundation for future work investigating NnaR's contribution to pathogenesis.
Topics: Mycobacterium abscessus; Nitrates; Gene Expression Regulation, Bacterial; Nitrites; Bacterial Proteins; Humans; Mycobacterium Infections, Nontuberculous; Nitrite Reductases; Nitrate Reductase
PubMed: 38854658
DOI: 10.3389/fcimb.2024.1411333 -
BMC Microbiology Jun 2024The Non-tuberculous mycobacterial (NTM) isolates should be distinguished from tuberculosis and identified at the species level for choosing an appropriate treatment...
The Non-tuberculous mycobacterial (NTM) isolates should be distinguished from tuberculosis and identified at the species level for choosing an appropriate treatment plan. In this study, two molecular methods were used to differentiate NTM species, including a new designed High Resolution Melting (HRM) and Multilocus Sequence Analysis (MLSA). Seventy-five mycobacterial isolates were evaluated by sequencing four genes ( MLSA) and a HRM assay specifically targeting atpE was designed to rapidly and accurately identify and differentiate mycobacterium species. Out of 70 NTM isolates, 66 (94.3%), 65 (92.9%), 65 (92.9%) and 64 (91.4%) isolates were identified to the species level by PCR of atpE, tuf, rpoB and dnaK genes. We could identify 100% of the isolates to the species level (14 different species) by MLSA. By using HRM assay, all NTM isolates were identified and classified into eight groups, in addition, Mycobacterium tuberculosis and Nocardia were also detected simultaneously. The MLSA technique was able to differentiate all 14 species of NTM isolates. According to the results, the HRM assay is a rapid and beneficial method for identifying NTM, M. tuberculosis (MTB), and Nocardia isolates without sequencing.
Topics: Humans; Multilocus Sequence Typing; Transition Temperature; Mycobacterium; Bacterial Proteins; Nontuberculous Mycobacteria; DNA, Bacterial; Mycobacterium Infections, Nontuberculous
PubMed: 38851713
DOI: 10.1186/s12866-024-03361-x -
Diagnostic Microbiology and Infectious... May 2024We present a patient who suffered an agricultural rollover trauma and developed a fracture-associated tissue infection caused by Mycobacterium smegmatis. Since cases are...
We present a patient who suffered an agricultural rollover trauma and developed a fracture-associated tissue infection caused by Mycobacterium smegmatis. Since cases are rare, treatment of infections with M. smegmatis requires an interprofessional approach and the combination of surgery and adjunctive antimicrobial treatment.
PubMed: 38850688
DOI: 10.1016/j.diagmicrobio.2024.116379