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Frontiers in Immunology 2022Anti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human...
BACKGROUND
Anti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data.
METHODS
This systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity.
RESULTS
We included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%).
CONCLUSIONS
Intracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, , and spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases.
Topics: Adult; Humans; Adolescent; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Autoantibodies; Rituximab; Nontuberculous Mycobacteria; Immunotherapy; Cyclophosphamide; HIV Infections; Multicenter Studies as Topic
PubMed: 36569827
DOI: 10.3389/fimmu.2022.1051673 -
The Journal of Infection Sep 2023Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
METHODS
We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961.
RESULTS
Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5).
CONCLUSION
Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
Topics: Humans; Adult; Pregnancy; Female; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Antitubercular Agents
PubMed: 37356629
DOI: 10.1016/j.jinf.2023.06.014 -
The Journal of Infection Jun 2024The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this... (Review)
Review
INTRODUCTION
The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium.
METHODS
A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed.
RESULTS
One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively).
CONCLUSION
In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.
PubMed: 38906266
DOI: 10.1016/j.jinf.2024.106203 -
International Journal of... 2023Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium... (Review)
Review
Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with β-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a β-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.
Topics: Humans; beta-Lactamase Inhibitors; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium tuberculosis; Carbapenems; Penicillins; Clavulanic Acid; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous
PubMed: 37721224
DOI: 10.4103/ijmy.ijmy_131_23 -
International Journal of... 2021Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) remain the leading causes of lung disease and mortality worldwide. Interferon-gamma (IFN-γ) and... (Review)
Review
Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) remain the leading causes of lung disease and mortality worldwide. Interferon-gamma (IFN-γ) and its receptor (IFN-γR) play a key role in mediating immunity against Mtb and NTM. This study was conducted as a systematic review; all information was collected from databases such as: PubMed, Scopus, Medline, SID, and medical databases. Finally, all the collected data were reviewed, and all content was categorized briefly. There is growing evidence that IFN-γ plays an important role in host defense against these two intracellular pathogens by activating macrophages. In addition, IFN-γ has been shown to be an integral part of various antibacterial methods such as granuloma formation and phagosome-lysosome fusion, both of which lead to the death of intracellular Mycobacterium. As a result, its absence is associated with overgrowth of intracellular pathogens and disease caused by Mtb or Mycobacterium nontuberculosis. We also look at the role of IFN-γR in Mtb or NTM because IFN-γ acts through IFN-γR. Finally, we introduce new approaches to the treatment of M. tuberculosis complex (MTC) and NTM disease, such as cell and gene-based therapies that work by modulating IFN-γ and IFN-γR.
Topics: Humans; Interferon-gamma; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Receptors, Interferon; Tuberculosis; Interferon gamma Receptor
PubMed: 34916451
DOI: 10.4103/ijmy.ijmy_186_21 -
World Journal of Orthopedics May 2022() is an emerging cause of hip and knee prosthetic joint infection (PJI), and different species of this organism may be responsible for the same.
BACKGROUND
() is an emerging cause of hip and knee prosthetic joint infection (PJI), and different species of this organism may be responsible for the same.
AIM
To evaluate the profile of hip and knee PJI cases as published in the past 30 years.
METHODS
A literature search was performed in PubMed using the MeSH terms "Prosthesis joint infection" AND "Mycobacterium" for studies with publication dates from January 1, 1990, to May 30, 2021. To avoid missing any study, another search was performed with the terms "Arthroplasty infection" AND "Mycobacterium" in the same period as the previous search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses chart was used to evaluate the included studies for further review. In total, 51 studies were included for further evaluation of the cases, type of pathogen, and treatment of PJI caused by .
RESULTS
Seventeen identified were reportedly responsible for hip/knee PJI in 115 hip/knee PJI cases, whereas in two cases there was no mention of any specific () was detected in 50/115 (43.3%) of the cases. Nontuberculous mycobacteria (NTM) included (26/115, 22.6%), (10/115, 8.6%), (8/115, 6.9%), and (8/115, 6.9%). Majority of the cases (82/114, 71.9%) had an onset of infection > 3 mo after the index surgery, while in 24.6% (28/114) the disease had an onset in ≤ 3 mo. Incidental intraoperative PJI diagnosis was made in 4 cases (3.5%). Overall, prosthesis removal was needed in 77.8% (84/108) of the cases to treat the infection. Overall infection rate was controlled in 88/102 (86.3%) patients with PJI. Persistent infection occurred in 10/108 (9.8%) patients, while 4/108 (3.9%) patients died due to the infection.
CONCLUSION
At least 17 can be responsible for hip/knee PJI. Although is the most common causal pathogen, NTM should be considered as an emerging cause of hip/knee PJI.
PubMed: 35633748
DOI: 10.5312/wjo.v13.i5.503 -
One Health (Amsterdam, Netherlands) Jun 2023() disease is an important infection disease throughout the world. () is a common . Extrapulmonary infections due to , particularly spine infections, are a rare...
BACKGROUND AND PURPOSE
() disease is an important infection disease throughout the world. () is a common . Extrapulmonary infections due to , particularly spine infections, are a rare occurrence, but lack of research is cited as a constraint for implementing control in such patients. The purposes of this paper are to describe a case of spondylodiscitis, to review the published literature on cases of spine infections, and to summarize the predisposing factors, diagnosis, and treatment of infection.
METHODS
A case of spondylodiscitis was caused by in a patient with systemic lupus erythematosus (SLE). Research was conducted using the PubMed, ScienceDirect, Embase, Wiley Online Library, and Scopus databases using the following search terms: "", "vertebral", "spinal", "spondylodiscitis", "infection", and "osteomyelitis".
RESULTS
We retrieved 14 cases published before August 2022. The risk factors for infection were iatrogenic infections (3/14, 21.43%), SLE (4/14, 28.57%), AIDS (4/14, 28.57%), and immunocompetence without any comorbidities (3/14, 21.43%). The most common sites of infection were thoracic vertebrae (10/14, 71.43%) and lumbar vertebrae (4/14, 28.57%). A total of 14 cases were isolated and identified as from a toad by mycobacterial culture. The identification time was 55.00 ± 7.55 days (the present report identification time of metagenomic next generation sequencing (mNGS) was only 2 days). All patients were treated with antibiotic therapy, and the duration of treatment was 13.18 ± 2.13 months. Clarithromycin-based therapy showed a higher improvement rate (5/6, 83.33%). Surgical intervention was performed in 5 patients. Only 1 patient did not show any improvement after surgical treatment.
CONCLUSION
spine infection in humans presents with atypical clinical symptoms. mNGS identification may be a good choice. may be considered in immunocompromised patients with spinal infection. We recommend a clarithromycin-containing regimen and prolonging the duration of treatment to ensure effectiveness.
PubMed: 36817979
DOI: 10.1016/j.onehlt.2023.100502 -
Future Medicinal Chemistry Apr 2024The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the genus. According to the Preferred... (Review)
Review
The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the genus. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant on membranes and biofilms. approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.
Topics: Molecular Docking Simulation; Cymenes; Mycobacterium tuberculosis; Anti-Bacterial Agents
PubMed: 38390753
DOI: 10.4155/fmc-2023-0249 -
PLoS Neglected Tropical Diseases Apr 2020Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after... (Meta-Analysis)
Meta-Analysis
Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after tuberculosis (TB) and leprosy. The available methods for detection of the bacilli in lesions are microscopic detection, isolation and cultivation of the bacterium, histopathology, and polymerase chain reaction (PCR). These methods, although approved by the World Health Organization (WHO), have infrastructural and resource challenges in medical centres and cell-mediated immunity (CMI) and/or serology-based tests have been suggested as easier and more appropriate for accurate assessment of the disease, especially in remote or underdeveloped areas. This study systematically reviewed and conducted a meta-analysis for all research aimed at developing cell-mediated immunity (CMI) and/or serology-based tests for M. ulcerans disease. Information for this review was searched through PubMed and Web of Science databases and identified up to June 2019. References from relevant articles and reports from the WHO Annual Meeting of the Global Buruli Ulcer Initiative were also used. Twelve studies beginning in 1952, that attempted to develop CMI and/or serology-based tests for the disease were identified. These studies addressed issues of specificity and sensitivity in context of antigen composition as well as study heterogeneity and bias. The two main types of antigenic preparations considered were pathogen-derived and recombinant protein preparations. There was slight difference in test performance when M. ulcerans recombinant proteins [positivity: 67.5%; 32.5%] or pathogen-derived [positivity: 76.0%; 24.0%] preparations were used as test antigens among BU patients. However, pathogen-derived preparations were better at differentiating between patients and control groups [odds ratio (OR) of 27.92, 95%CI: 5.05-154.28]. This was followed by tests with the recombinant proteins [OR = 1.23, 95%CI: 0.27-5.62]. Overall, study heterogeneity index, I2 was 92.4% (p = 0.000). It is apparent from this review that standardisation is needed in any future CMI and/or serology-based tests used for M. ulcerans disease.
Topics: Buruli Ulcer; Databases, Factual; Humans; Immunity, Cellular; Leprosy; Mycobacterium ulcerans; Polymerase Chain Reaction; Serologic Tests
PubMed: 32251470
DOI: 10.1371/journal.pntd.0008172 -
ERJ Open Research Jan 2023People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We... (Review)
Review
BACKGROUND
People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of NTM in the cystic fibrosis population.
METHODS
Electronic databases, registries and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease in cystic fibrosis. The last search was conducted in September 2021; we included reports published since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random effects meta-analysis was conducted to summarise the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis.
RESULTS
This review included 95 studies. All 95 studies reported on NTM infection, and 14 of these also reported on NTM pulmonary disease. The pooled estimate for the point prevalence of NTM infection was 7.9% (95% CI 5.1-12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019.
CONCLUSIONS
The overall prevalence of NTM infection in cystic fibrosis is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods and incidence rates of progression from NTM infection to pulmonary disease.
PubMed: 36605902
DOI: 10.1183/23120541.00336-2022