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European Journal of Case Reports in... 2024Blue rubber bleb nevus syndrome is a rare disorder of venous malformations, with around 200 cases reported. We present a case of infection in a patient with blue rubber...
INTRODUCTION
Blue rubber bleb nevus syndrome is a rare disorder of venous malformations, with around 200 cases reported. We present a case of infection in a patient with blue rubber bleb nevus syndrome.
CASE DESCRIPTION
A 40-year-old female with blue rubber bleb nevus syndrome, asthma, and bronchiectasis came to the pulmonology clinic with shortness of breath and a cough. She was recently admitted for a bronchiectasis exacerbation but continued to have a worsening productive cough and fevers. The most recent CT scan of the chest showed interval stable right upper lobe fibrocavitary disease, demonstrating gradual progression over two years. She had occasional positive cultures for and one year previously, assumed to be a colonizer and not treated. Most recent hospital cultures were negative for bacteria and an acid-fast bacilli smear. She was sent to the emergency department for bronchiectasis exacerbation and returned to the clinic six weeks later with two sputum cultures growing . It was decided to treat as this was likely the cause of her cavitary lung lesion and frequent infections. Azithromycin, rifampin, and sulfamethoxazole/trimethoprim were initiated. Intravenous amikacin was added later on. She finally had a right partial lung resection done after one year at an outside hospital. She was on and off antibiotics for for approximately three years with negative repeat cultures for non-tuberculous mycobacteria.
CONCLUSION
Due to the high mortality of infections (which can be as high as 69%), treatment of at least twelve months is recommended. To our knowledge, this is the first reported case of in a patient with blue rubber bleb nevus syndrome.
LEARNING POINTS
The decision to initiate treatment for non-tuberculous mycobacterium infections is often challenging with prolonged treatment.Lifetime monitoring is required in patients with blue rubber bleb nevus syndrome, which can have pulmonary complications. has the highest mortality among non-tuberculous mycobacterium infections and requires at least 12 months of treatment.
PubMed: 38846651
DOI: 10.12890/2024_004530 -
Heliyon Jun 2024The prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly...
BACKGROUND
The 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.
METHODS
English 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 I statistic. All analyses were performed using CMA V3.0.
RESULTS
The 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 %). complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%-69.6 %). Inconsistent with adult patients, accounted for a dominant proportion in MAC than .
CONCLUSIONS
The lymph node was the most affected organ in pediatric NTM disease, while was the most isolated pathogenic species in children.
PubMed: 38845977
DOI: 10.1016/j.heliyon.2024.e31757 -
Journal of the American Academy of... Jun 2024
PubMed: 38844008
DOI: 10.1016/j.jaad.2024.05.070 -
Microbiology Spectrum Jul 2024Non-tuberculosis mycobacteria (NTM), particularly subsp. (), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment...
UNLABELLED
Non-tuberculosis mycobacteria (NTM), particularly subsp. (), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment options for are limited owing to their natural resistance to most antibiotics, including β-lactams. produces a class A β-lactamase, whose activity is inhibited by cyclic boronic acid β-lactamase inhibitors. We aimed to evaluate the effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor, against when combined with five β-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). The drug susceptibilities of 43 . clinical isolates obtained from 43 patients between August 2005 and May 2014 were tested. The MIC results for each β-lactam with or without 4 µg/mL xeruborbactam were examined. Xeruborbactam lowered the MIC values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC values of cefoxitin without xeruborbactam were 32 µg/mL and did not change upon the addition of xeruborbactam. The lowest MIC value was obtained for tebipenem with xeruborbactam. Almost all isolates had an MIC of 4 µg/mL; one isolate had an MIC of 2 µg/mL. With respect to the susceptibility to the same family drug, the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%) for tebipenem with xeruborbactam. Combining tebipenem and xeruborbactam could be considered an effective all-oral regimen that benefits outpatient treatment of pulmonary disease.
IMPORTANCE
subsp. () disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for infection, especially in the continuation phase. However, treatment options for are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid β-lactamase inhibitor capable of inhibiting the class A β-lactamase produced by , against 43 clinical isolates when combined with five β-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of pulmonary disease.
Topics: Humans; Mycobacterium abscessus; beta-Lactamase Inhibitors; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Anti-Bacterial Agents; beta-Lactams; Boronic Acids
PubMed: 38842354
DOI: 10.1128/spectrum.00084-24 -
Antimicrobial Agents and Chemotherapy Jun 2024Individuals with compromised lung function and immunity are susceptible to developing chronic infection. Current treatment recommendations typically involve using one...
Individuals with compromised lung function and immunity are susceptible to developing chronic infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for infections.
PubMed: 38837394
DOI: 10.1128/aac.00585-24 -
Tuberculosis and Respiratory Diseases Jun 2024Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroids (ICS). However,...
BACKGROUND
Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroids (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases.
METHODS
We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability treatment weighting (IPTW) to ensure a balanced analysis of covariates.
RESULTS
Of the 57,553 patients (mean age: 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including 9 among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI]: 7.48-15.58). Higher risks were significant for patients ≥65 years (adjusted HR: 6.40, 95% CI: 1.28-31.94), females (adjusted HR: 10.91, 95% CI: 2.24-53.20), never-smokers (adjusted HR: 6.31, 95% CI: 1.49-26.64), systemic steroid users (adjusted HR: 50.19, 95% CI: 8.07-312.19), and those with higher comorbidity scores (adjusted HR: 6.64, 95% CI: 1.19-37.03).
CONCLUSION
ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.
PubMed: 38835294
DOI: 10.4046/trd.2024.0038 -
Drug Discovery Today Jun 2024Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising.... (Review)
Review
Tuberculosis (TB) is a significant global health threat, and cases of infection with non-tuberculous mycobacteria (NTM) causing lung disease (NTM-LD) are rising. Bacteriophages and their gene products have garnered interest as potential therapeutic options for bacterial infections. Here, we have compiled information on bacteriophages and their products that can kill Mycobacterium tuberculosis or NTM. We summarize the mechanisms whereby viable phages can access macrophage-resident bacteria and not elicit immune responses, review methodologies of pharmaceutical product development containing mycobacteriophages and their gene products, mainly lysins, in the context of drug regulatory requirements and we discuss industrially relevant methods for producing pharmaceutical products comprising mycobacteriophages, emphasizing delivery of mycobacteriophages to the lungs. We conclude with an outline of some recent case studies on mycobacteriophage therapy.
PubMed: 38830505
DOI: 10.1016/j.drudis.2024.104049 -
Journal of Clinical Tuberculosis and... Aug 2024There are different tuberculosis diagnostic tools available that detect an antigen-specific immune response. The present study aims to evaluate the potential of...
There are different tuberculosis diagnostic tools available that detect an antigen-specific immune response. The present study aims to evaluate the potential of cross-reactive responses of a CFP-10 and ESAT-6 antigen-based TB test using bioinformatics tools. The study found that the presence of the sequences coding for the CFP-10 and ESAT-6 antigens in mycobacterial genomes is not associated with their pathogenicity, and not even consistent within a single species among its strains, which can lead to either false positive or false negative test results. The data that was analyzed included genome assemblies of all available mycobacterial strains obtained from the NCBI Genome database, while the standalone BLAST and tblastn programs were utilized to detect the presence of the CFP-10 and ESAT-6 sequences. The findings revealed that a number of non-pathogenic mycobacteria contained the aforementioned sequences, while some pathogenic mycobacteria did not, indicating that a standard tuberculin skin test should be more preferable for detecting various pathogenic mycobacteria compared to antigen-specific tests. In the complex (MTBC), the proportion of positive strains varied within individual species, indicating a complex relationship. Among non-tuberculous mycobacteria (NTMB), more than half of the analyzed species did not contain these sequences which is consistent with their non-pathogenicity. Further research is necessary to fully comprehend the relationship between MTBC pathogenicity and the CFP-10 and ESAT-6 sequences. This could lead to a conclusion that a standard tuberculin skin test, although non-specific due to the undefined antigen content, may be able to detect various pathogenic mycobacteria in a more reliable manner than antigen-specific tests.
PubMed: 38828192
DOI: 10.1016/j.jctube.2024.100436 -
International Journal of Biological... Jun 2024Due to the uniqueness and essentiality of MEP pathway for the synthesis of crucial metabolites- isoprenoids, hopanoids, menaquinone etc. in mycobacterium, enzymes of...
Due to the uniqueness and essentiality of MEP pathway for the synthesis of crucial metabolites- isoprenoids, hopanoids, menaquinone etc. in mycobacterium, enzymes of this pathway are considered promising anti-tubercular drug targets. In the present study we seek to understand the consequences of downregulation of three of the essential genes- DXS, IspD, and IspF of MEP pathway using CRISPRi approach combined with transcriptomics in Mycobacterium smegmatis. Conditional knock down of either DXS or IspD or IspF gene showed strong bactericidal effect and a profound change in colony morphology. Impaired MEP pathway due to downregulation of these genes increased the susceptibility to frontline anti-tubercular drugs. Further, reduced EtBr accumulation in all the knock down strains in the presence and absence of efflux inhibitor indicated altered cell wall topology. Subsequently, transcriptional analysis validated by qRT-PCR of +154DXS, +128IspD, +104IspF strains showed that modifying the expression of these MEP pathway enzymes affects the regulation of mycobacterial core components. Among the DEGs, expression of small and large ribosomal binding proteins (rpsL, rpsJ, rplN, rplX, rplM, rplS, etc), essential protein translocases (secE, secY and infA, infC), transcriptional regulator (CarD and SigB) and metabolic enzymes (acpP, hydA, ald and fabD) were significantly depleted causing the bactericidal effect. However, mycobacteria survived under these damaging conditions by upregulating mostly the genes needed for the repair of DNA damage (DNA polymerase IV, dinB), synthesis of essential metabolites (serB, LeuA, atpD) and those strengthening the cell wall integrity (otsA, murA, D-alanyl-D-alanine dipeptidase etc.).
Topics: Bacterial Proteins; Mycobacterium smegmatis; Gene Expression Regulation, Bacterial; Antitubercular Agents; Microbial Viability; Metabolic Networks and Pathways
PubMed: 38823743
DOI: 10.1016/j.ijbiomac.2024.132727 -
International Journal of Infectious... May 2024Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune...
Clinical features and treatment outcomes of bone and joint nontuberculous mycobacterial infections according to immune status: a 9-year retrospective observational cohort.
OBJECTIVES
Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status.
METHODS
We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients.
RESULTS
Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group.
CONCLUSIONS
Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.
PubMed: 38823623
DOI: 10.1016/j.ijid.2024.107122