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Tuberculosis and Respiratory Diseases Apr 2024Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), there are geographical variations in clinical characteristics. We investigated...
RATIONALE
Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), there are geographical variations in clinical characteristics. We investigated the clinical characteristics of patients with NTM-PD in South Korea.
METHODS
We systematically reviewed articles about patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form.
RESULTS
The data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5 ± 11.7 years, and 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and Mycobacterium abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Reported cases of NTM-PD increased over the years, but the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 vs. 59.9 years, P<0.001) and had more cavitary lesions than women (38.8% vs. 21.0%, P<0.001). The older group (≥65 years) had a higher proportion of patients with body mass index <18.5 kg/m2 (27.4% vs. 18.6%, P<0.001) and cavitary lesions (29.9% vs. 27.6%, P=0.009) than the younger group.
CONCLUSION
We performed a meta-analysis of the clinical characteristics of patients with NTM-PD in South Korea. We found age- and sex-related differences in disease-specific severity. Further investigation would enhance our comprehension of the disease's nature and inherited and acquired host factors.
PubMed: 38590075
DOI: 10.4046/trd.2023.0193 -
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 -
Frontiers in Microbiology 2024Although the incidence of infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In...
Although the incidence of infection has recently increased significantly, treatment is difficult because this bacterium is resistant to most anti-tuberculosis drugs. In particular, is often resistant to available macrolide antibiotics, so therapeutic options are extremely limited. Hence, there is a pressing demand to create effective drugs or therapeutic regimens for infections. The aim of the investigation was to assess the capability of isoegomaketone (iEMK) as a therapeutic option for treating infections. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of iEMK for both reference and clinically isolated strains. In addition to time-kill and biofilm formation assays, we evaluated iEMK's capability to inhibit growth in macrophages using an intracellular colony counting assay. iEMK inhibited the growth of reference and clinically isolated strains in macrophages and demonstrated effectiveness at lower concentrations against macrophage-infected than when used to treat the bacteria directly. Importantly, iEMK also exhibited anti-biofilm properties and the potential to mitigate macrolide-inducible resistance, underscoring its promise as a standalone or adjunctive therapeutic agent. Overall, our results suggest that further development of iEMK as a clinical drug candidate is promising for inhibiting growth, especially considering its dual action against both planktonic bacteria and biofilms.
PubMed: 38585695
DOI: 10.3389/fmicb.2024.1344914 -
Journal of Ethnopharmacology Jul 2024Psoralea corylifolia L. (Fabaceae) is a traditional medicinal herb used to treat various diseases, including kidney disease, asthma, psoriasis and vitiligo.
ETHNOPHARMACOLOGICAL RELEVANCE
Psoralea corylifolia L. (Fabaceae) is a traditional medicinal herb used to treat various diseases, including kidney disease, asthma, psoriasis and vitiligo.
AIM OF THE STUDY
To explore the antibacterial activity of Psoralea corylifolia L. and its bioactive components against Mycobacterium abscessus (M. abscessus).
MATERIALS AND METHODS
Ultra high performance liquid chromatography was utilized to analyze the bioactive fractions and compounds present in 30%, 60%, and 90% ethanol extracts of Psoralea corylifolia L.. The antibacterial effects of Psoralea corylifolia L. and potential active ingredients were determined by minimum inhibitory concentration (MIC). The bactericidal activity of the active ingredient isobavachalcone was evaluated and then scanning electron microscopy was used to explore the bactericidal mechanism of isobavachalcone.
RESULTS
The 90% ethanol extracts of Psoralea corylifolia L. showed significant antibacterial activity against M. abscessus, with an MIC of 156 μg/mL. Isobavachalcone was identified as the bioactive ingredient, and testing of 118 clinical isolates of M. abscessus indicated their MICs ranged from 2 to 16 μg/mL, with an average MIC of 8 μg/mL. Furthermore, the minimum bactericidal concentration/MIC ratio and the time-kill test indicated rapid bactericidal activity of isobavachalcone against M. abscessus. Finally, we found that the bactericidal mechanism of isobavachalcone involved damage to the bacterial cell membrane, causing wrinkled and sunken cell surface and a noticeable reduction in bacterial length.
CONCLUSION
Psoralea corylifolia L. ethanol extracts as well as its active component isobavachalcone show promising antimicrobial activity against M. abscessus.
Topics: Psoralea; Microbial Sensitivity Tests; Anti-Bacterial Agents; Plant Extracts; Chalcones; Mycobacterium abscessus
PubMed: 38583730
DOI: 10.1016/j.jep.2024.118142 -
CEN Case Reports Apr 2024Most peritoneal dialysis (PD)-associated infections caused by Mycobacterium abscessus (M. abscessus) require a transfer from PD to hemodialysis (HD). Here, we report a...
Most peritoneal dialysis (PD)-associated infections caused by Mycobacterium abscessus (M. abscessus) require a transfer from PD to hemodialysis (HD). Here, we report a pediatric case of exit-site and tunnel infections caused by M. abscessus, for whom PD was continued with catheter replacement, debridement of the infected site, and the administration of multiple antibacterial agents. A 10-year-old boy with end-stage kidney disease secondary to juvenile nephronophthisis with NPHP1 deletion, for whom PD was initiated at the age of 9 years, was admitted to the hospital with complaints of fever, pus at the exit-site of the PD catheter, and poor PD drainage. The dialysis effluent culture results were negative; however, M. abscessus was detected in the pus at the exit-site of the PD catheter. The management of HD was expected to be challenging owing to the presence of developmental disorders. Therefore, PD was continued with the simultaneous removal of the PD catheter, reinsertion of a new catheter at a new site, and debridement of the infected site. Multiple antibacterial therapies were administered for 2 months, and the patient was eventually discharged without switching to HD. To the best of our knowledge, this is the first pediatric case of a PD-associated infection caused by M. abscessus, for whom PD was continued without switching to HD. This treatment strategy is not generally recommended but may be an option for patients without peritonitis who have difficulty switching to HD.
PubMed: 38581567
DOI: 10.1007/s13730-024-00875-1 -
ACS Infectious Diseases May 2024Treatment of microbial infections is becoming daunting because of widespread antimicrobial resistance. The treatment challenge is further exacerbated by the fact that...
Treatment of microbial infections is becoming daunting because of widespread antimicrobial resistance. The treatment challenge is further exacerbated by the fact that certain infectious bacteria invade and localize within host cells, protecting the bacteria from antimicrobial treatments and the host's immune response. To survive in the intracellular niche, such bacteria deploy surface receptors similar to host cell receptors to sequester iron, an essential nutrient for their virulence, from host iron-binding proteins, in particular lactoferrin and transferrin. In this context, we aimed to target lactoferrin receptors expressed by macrophages and bacteria; as such, we prepared and characterized lactoferrin nanoparticles (Lf-NPs) loaded with a dual drug combination of antimicrobial natural alkaloids, berberine or sanguinarine, with vancomycin or imipenem. We observed increased uptake of drug-loaded Lf-NPs by differentiated THP-1 cells with up to 90% proportion of fluorescent cells, which decreased to about 60% in the presence of free lactoferrin, demonstrating the targeting ability of Lf-NPs. The encapsulated antibiotic drug cocktail efficiently cleared intracellular (Newman strain) compared to the free drug combinations. However, the encapsulated drugs and the free drugs alike exhibited a bacteriostatic effect against the hard-to-treat (smooth variant). In conclusion, the results of this study demonstrate the potential of lactoferrin nanoparticles for the targeted delivery of antibiotic drug cocktails for the treatment of intracellular bacteria.
Topics: Lactoferrin; Humans; Nanoparticles; Staphylococcus aureus; Anti-Bacterial Agents; THP-1 Cells; Macrophages; Vancomycin; Drug Carriers; Drug Delivery Systems; Microbial Sensitivity Tests
PubMed: 38577780
DOI: 10.1021/acsinfecdis.4c00045 -
Journal of Global Antimicrobial... Jun 2024This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections.
METHODS
We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I statistic. All analyses were performed using CMA V3.0.
RESULTS
A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively.
CONCLUSION
This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.
Topics: Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium Infections, Nontuberculous; Antitubercular Agents; Drug Resistance, Bacterial; Mycobacterium avium-intracellulare Infection
PubMed: 38561143
DOI: 10.1016/j.jgar.2024.03.009 -
Infection and Drug Resistance 2024In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM...
BACKGROUND
In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving (MABC) infection where effective therapeutic options are limited.
CASE PRESENTATION
We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened.
CONCLUSION
This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.
PubMed: 38560704
DOI: 10.2147/IDR.S453541 -
MethodsX Jun 2024is one of the most important nontuberculous mycobacteria that cause lung diseases. infection models developed to analyze the immune response are frequently based on...
is one of the most important nontuberculous mycobacteria that cause lung diseases. infection models developed to analyze the immune response are frequently based on the addition of mycobacteria to mononuclear cells or neutrophils from peripheral blood. An important requirement of these assays is that most cells phagocytose mycobacteria, only accomplished by using large multiplicities of infection (1 or more bacteria per cell) which may not adequately reflect the inhalation of a few mycobacteria by the host. We propose modifications that try to mimic some of the conditions in which immune cells deal with mycobacteria. For the preparation of the inoculum mycobacteria are grown in solid media followed by preparation to a single cell suspension. Multiplicities of infection (number of bacteria per cell) are below 0.01. Serum-free cellular media is used to allow the growth of . After several days of incubation Bacterial Colonies in Cellular Culture (BCCC) develop, which are enumerated directly under an inverted microscope. These colonies may represent biofilm formation during chronic infections. •Low multiplicity of infection (below 0.01 bacteria per cell) reflects more realistically conditions encountered by immune cells in the lungs.•The surface of mycobacteria prepared for infection assays that are grown in solid media are less affected than that of mycobacteria grown in liquid media with detergents.•Colony formation in the infected cells may reflect the aggregation and biofilm formation in the lungs during chronic infection.
PubMed: 38559385
DOI: 10.1016/j.mex.2024.102667 -
Nature Communications Mar 2024Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent...
Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.
Topics: Humans; Mycobacterium abscessus; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous; Macrolides; Phylogeny; Persistent Infection; Reinfection; Drug Resistance, Bacterial; Genomics; Microbial Sensitivity Tests
PubMed: 38548737
DOI: 10.1038/s41467-024-46552-w