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Frontiers in Cellular and Infection... 2023Nocardiosis is an infectious disease caused by that primarily affects immunocompromised hosts. is a common opportunistic pathogen that causes disease in humans,...
Nocardiosis is an infectious disease caused by that primarily affects immunocompromised hosts. is a common opportunistic pathogen that causes disease in humans, including pulmonary and extrapulmonary infection. spp. infection is uncommon, and infection with and is even rarer. A 59-year-old immunocompetent woman with risk factors for environmental exposure developed nocardiosis and presented to the hospital with a cough, shortness of breath, hemoptysis, and a back abscess. An enhanced computed tomography (CT) of the chest revealed partial destruction of the right lung, as well as consolidation of the right upper lobe. Rare pathogens and were detected by metagenomic next-generation sequencing (mNGS) from abscess on the back and lung puncture tissue, respectively. She was treated with a combination of antibiotics and was finally discharged with a good prognosis. In this case, we present a patient who was successfully diagnosed with and infection using mNGS. This importance of using mNGS in pathogen detection and the effective use of antibiotics in treating patients with long-term rare infections is highlighted in this report.
Topics: Female; Humans; Middle Aged; Mycobacterium abscessus; Abscess; East Asian People; Nocardia; Nocardia Infections; Anti-Bacterial Agents; Lung
PubMed: 37655298
DOI: 10.3389/fcimb.2023.1229298 -
American Journal of Respiratory and... Jul 2024
Topics: Humans; Bronchiectasis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Male; Female
PubMed: 38747644
DOI: 10.1164/rccm.202405-0936ED -
Clinical Microbiology and Infection :... Jun 2024Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual β-lactam and β-lactam/β-lactamase inhibitor... (Review)
Review
BACKGROUND
Antibiotic treatment of Mycobacterium abscessus disease is toxic and poorly effective and lacks a firm evidence base. Dual β-lactam and β-lactam/β-lactamase inhibitor combinations may be interesting leads to improve treatment outcomes.
OBJECTIVES
To summarize the current preclinical studies on dual β-lactam and β-lactam/β-lactamase inhibitor combinations against M. abscessus.
SOURCES
We performed a literature search using the National Center for Biotechnology Information's PubMed interface with additional snowball sampling.
CONTENT
Select combinations of β-lactam antibiotics, as well as β-lactam/β-lactamase inhibitor combinations show promising in vitro activity and synergy against M. abscessus. β-Lactam antibiotics differ in their ability to reach and interfere with their targets and their resistance to the M. abscessus β-lactamase. The synergy is typically observed for combinations of β-lactam antibiotics or a β-lactam antibiotic with a β-lactamase inhibitor. No additional killing capacity was demonstrated in three-drug combinations of synergistic β-lactam antibiotics and a β-lactamase inhibitor. The efficacy of select dual β-lactam antibiotics and β-lactam/β-lactamase inhibitor combinations is retained in intracellular infection assays and mouse models, but no combination has a complete preclinical portfolio.
IMPLICATIONS
Future clinical strategies should entail either dual β-lactam or β-lactam/β-lactamase inhibitor combinations. Imipenem-ceftaroline and an all-oral tebipenem-avibactam combination are promising leads but still require a complete preclinical portfolio, target product profiles as well as clinical trial confirmation.
Topics: Mycobacterium abscessus; beta-Lactams; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; beta-Lactamase Inhibitors; Humans; Treatment Outcome; Drug Therapy, Combination; Drug Synergism; Animals; Microbial Sensitivity Tests
PubMed: 38527611
DOI: 10.1016/j.cmi.2024.03.019 -
Nature Communications Mar 2024Natural fruits contain a large variety of cis-diols. However, due to the lack of a high-resolution sensor that can simultaneously identify all cis-diols without a need...
Natural fruits contain a large variety of cis-diols. However, due to the lack of a high-resolution sensor that can simultaneously identify all cis-diols without a need of complex sample pretreatment, direct and rapid analysis of fruits in a hand-held device has never been previously reported. Nanopore, a versatile single molecule sensor, can be specially engineered to perform this task. A hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore modified with a sole phenylboronic acid (PBA) adapter is prepared. This engineered MspA accurately recognizes 1,2-diphenols, alditols, α-hydroxy acids and saccharides in prune, grape, lemon, different varieties of kiwifruits and commercial juice products. Assisted with a custom machine learning program, an accuracy of 99.3% is reported and the sample pretreatment is significantly simplified. Enantiomers such as DL-malic acids can also be directly identified, enabling sensing of synthetic food additives. Though demonstrated with fruits, these results suggest wide applications of nanopore in food and drug administration uses.
Topics: United States; Fruit; Nanopores; Sugar Alcohols; Carboxylic Acids; Citrus; Mycobacterium smegmatis; Porins
PubMed: 38443434
DOI: 10.1038/s41467-024-46303-x -
Heliyon Apr 2024This study analyzed the laboratory diagnosis results and drug resistance of patients infected with (NTM).
BACKGROUND
This study analyzed the laboratory diagnosis results and drug resistance of patients infected with (NTM).
METHODS
We collected information on patients with positive indicators of NTM infection at the Henan Provincial Chest Hospital from 2020 to 2022. Acid-fast smear, mycobacterium culture, QB-SPOT assay, GeneXpert MTB/RIF assay, immunoglobulin E test, tuberculosis antibody test, and microplate method for drug sensitivity test were analyzed using strain identification as the gold standard.
RESULTS
The 242 cases of NTM infection were predominantly detected with slow-growing (a detection rate of 87.19%), among which (66.53%), (15.70%), and complex (11.16%) ranked the top three in terms of the isolation rate. Males patients accounted for a higher proportion (58.26%) than females (41.74%), and the majority of them were over 60 years (50.83%). Among laboratory tests for patients with NTM infection, mycobacterium culture showed a highest detected rate (87.20%) among laboratory tests. The results of the drug sensitivity test demonstrated that the resistance rate of NTM was generally high. Moreover, the complex with the highest isolation rate showed 100% resistant to doxycycline and minocycline, but exhibited relatively high sensitivity to moxifloxacin (a resistance rate of 7.89%) and rifabutin (a resistance rate of 13.16%). The complex was 100% resistant to doxycycline and relatively sensitive to cefoxitin (29.17%) and clarithromycin (37.50%).
CONCLUSION
The NTM species isolated by the Henan Provincial Chest Hospital is dominated by and the highest positive rate is detected by mycobacterium culture among laboratory tests. NTM infection generally exhibits a high rate of drug resistance. Accordingly, the accurate diagnosis of NTM diseases requires enhanced drug sensitivity testing to provide patients with targeted combination drug treatment.
PubMed: 38586355
DOI: 10.1016/j.heliyon.2024.e28665 -
Microbiology Spectrum Dec 2023Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the group have been steadily increasing in the USA and globally. Owing to the...
Difficult-to-treat pulmonary infections caused by nontuberculous mycobacteria of the group have been steadily increasing in the USA and globally. Owing to the relatively recent recognition of as a human pathogen, basic and translational research to address critical gaps in diagnosis, treatment, and prevention of diseases caused by this microorganism has been lagging behind that of the better-known mycobacterial pathogen, . To begin unraveling the molecular mechanisms of pathogenicity of , we here focus on the study of a two-component regulator known as PhoPR which we found to be under strong evolutionary pressure during human lung infection. We show that PhoPR is activated at acidic pH and serves to regulate a defined set of genes involved in host adaptation. Accordingly, clinical isolates from chronically infected human lungs tend to hyperactivate this regulator enabling to escape macrophage killing.
Topics: Humans; Host Adaptation; Hydrogen-Ion Concentration; Mutation; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Virulence; Protein Kinases
PubMed: 37874174
DOI: 10.1128/spectrum.01588-23 -
Frontiers in Cellular and Infection... 2023The advent of metagenomics next-generation sequencing (mNGS) has garnered attention as a novel method for detecting pathogenic infections, including Non-Tuberculous...
INTRODUCTION
The advent of metagenomics next-generation sequencing (mNGS) has garnered attention as a novel method for detecting pathogenic infections, including Non-Tuberculous Mycobacterial (NTM) and tuberculosis (TB).However, the robustness and specificity of mNGS in NTM diagnostics have not been fully explored.
METHODS
In this retrospective study, we enrolled 27 patients with NTM genomic sequences via mNGS and conducted a comprehensive clinical evaluation.
RESULTS
Pulmonary NTM disease was the most commonly observed presentation, with a subset of patients also presenting with extrapulmonary NTM infections.mNGS analysis identified six distinct NTM species, primarily Mycobacteriumavium complex (MAC), followed by Mycobacterium intracellulare andMycobacterium abscessus. Conventional routine culture methods encountered challenges, resulting in negative results for all available 22 samples. Among the 10 patients who underwent quantitative polymerase chain reaction (qPCR) testing, five tested positive for NTM.
DISCUSSION
It is important to note that further species typing is necessary to determine the specific NTM type, as traditional pathogen detection methods serve as an initial step. In contrast, when supplemented with pathogen data, enables the identification of specific species, facilitating precise treatment decisions. In conclusion, mNGS demonstrates significant potential in aidingthe diagnosis of NTMdisease by rapidly detecting NTM pathogens and guiding treatment strategies. Its enhanced performance, faster turnaround time (TAT), and species identification capabilities make mNGS a promising tool for managing NTM infections.
Topics: Humans; Nontuberculous Mycobacteria; Metagenomics; Retrospective Studies; Metagenome; High-Throughput Nucleotide Sequencing; Mycobacterium abscessus
PubMed: 37719673
DOI: 10.3389/fcimb.2023.1253020 -
Frontiers in Medicine 2023complex (MAC) is a type of nontuberculous mycobacteria (NTM) and is associated with underlying pulmonary diseases, such as chronic obstructive pulmonary disease,...
complex (MAC) is a type of nontuberculous mycobacteria (NTM) and is associated with underlying pulmonary diseases, such as chronic obstructive pulmonary disease, bronchiectasis, chronic aspiration or recurrent pneumonia, inactive or active tuberculosis, pneumoconiosis, and bronchogenic carcinoma. The risk factors for NTM-PD include host, drug, and environmental factors. In this report, we present the case of a 61-year-old man who developed bilateral lung nodules and was experiencing severe hemoptysis. The repeat acid-fast bacilli test performed on both sputum and bronchoalveolar lavage fluid (BALF) samples showed a negative result, as did the GeneXpert test. We employed metagenomic next-generation sequencing (mNGS) to analyze the lung nodule and BALF samples collected from the patient. Both samples tested positive for MAC within 3 days. In addition, traditional MAC culture, conducted for 2 months, confirmed the growth of MAC in the patient's BALF. Then, the patient was treated accordingly. Following treatment, a high-resolution chest computed tomography scan revealed a significant reduction in lung nodules of the patient after 2 months. These results indicate that MAC-associated lung nodules were responsible for the patient's symptoms, emphasizing the need for vigilance in diagnosing MAC infection in the patient without predisposing conditions. Furthermore, these results highlight the potential utility of mNGS as a promising rapid diagnostic tool for MAC infection and its potential role in the diagnosis of NTM disease.
PubMed: 37920597
DOI: 10.3389/fmed.2023.1247034 -
Nucleic Acids Research May 2024Bacteria have evolved structured RNAs that can associate with RNA polymerase (RNAP). Two of them have been known so far-6S RNA and Ms1 RNA but it is unclear if any other...
Bacteria have evolved structured RNAs that can associate with RNA polymerase (RNAP). Two of them have been known so far-6S RNA and Ms1 RNA but it is unclear if any other types of RNAs binding to RNAP exist in bacteria. To identify all RNAs interacting with RNAP and the primary σ factors, we have established and performed native RIP-seq in Bacillus subtilis, Corynebacterium glutamicum, Streptomyces coelicolor, Mycobacterium smegmatis and the pathogenic Mycobacterium tuberculosis. Besides known 6S RNAs in B. subtilis and Ms1 in M. smegmatis, we detected MTS2823, a homologue of Ms1, on RNAP in M. tuberculosis. In C. glutamicum, we discovered novel types of structured RNAs that associate with RNAP. Furthermore, we identified other species-specific RNAs including full-length mRNAs, revealing a previously unknown landscape of RNAs interacting with the bacterial transcription machinery.
Topics: Bacillus subtilis; Bacterial Proteins; Corynebacterium glutamicum; DNA-Directed RNA Polymerases; Gene Expression Regulation, Bacterial; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nucleic Acid Conformation; RNA, Bacterial; RNA, Untranslated; Sigma Factor; Streptomyces coelicolor; Transcription, Genetic
PubMed: 38348908
DOI: 10.1093/nar/gkae081 -
Emerging Microbes & Infections Dec 2023Numbers of non-tuberculous mycobacteria (NTM) pulmonary diseases (PD) have been repeatedly reported as increasing over the last decades, particularly in Europe. Sound...
Numbers of non-tuberculous mycobacteria (NTM) pulmonary diseases (PD) have been repeatedly reported as increasing over the last decades, particularly in Europe. Sound epidemiological data are however missing for most European regions. This study calculated prevalence and incidence of NTM recovered from patients' lungs in Germany, the largest Central European country, over a five-year period. It furthermore determined regional particularities of NTM species and results from susceptibility testing. 22 German NTM laboratories provided their mycobacteriological diagnostic data of 11,430 NTM isolates recovered from 5998 pulmonary patients representing 30% of all notified NTM-PD cases of Germany from 2016 to 2020. NTM incidence and prevalence were calculated for every study year. The presented epidemiological indicators are particularly reliant as TB surveillance data were used as a reference and TB notification reaches almost 100% in Germany. Laboratory incidence and prevalence of NTM recovered from respiratory samples ranged from 4.5-4.9 and from 5.3-5.8/100,000 for the population of Germany, respectively, and did not change over the five-year study period. Prevalence and incidence were stable also when stratifying for facultative pathogenic NTM, complex (MAIC), and complex (MABSC). The proportion of NTM with drug susceptibility testing (DST) increased from 27.3% (2016) to 43.8% (2020). The unchanging laboratory NTM prevalence/incidence in Germany represents a "ceiling" of possible NTM-PD notification when diagnostic strategies do not change in the coming years. A notable increase in NTM-DST may indicate better notification of NTM-PD and/or awareness of new clinical guidelines but still remains below clinical needs.
Topics: Humans; Nontuberculous Mycobacteria; Prevalence; Incidence; Laboratories; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Lung Diseases
PubMed: 37883336
DOI: 10.1080/22221751.2023.2276342