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Clinical Microbiology and Infection :... Nov 2021The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to... (Review)
Review
BACKGROUND
The fact that Mycobacterium leprae does not grow in vitro remains a challenge in the survey of its antimicrobial resistance (AMR). Mainly molecular methods are used to diagnose AMR in M. leprae to provide reliable data concerning mutations and their impact. Fluoroquinolones (FQs) are efficient for the treatment of leprosy and the main second-line drugs in case of multidrug resistance.
OBJECTIVES
This study aimed at performing a systematic review (a) to characterize all DNA gyrase gene mutations described in clinical isolates of M. leprae, (b) to distinguish between those associated with FQ resistance or susceptibility and (c) to delineate a consensus numbering system for M. leprae GyrA and GyrB.
DATA SOURCES
Data source was PubMed.
STUDY ELIGIBILITY CRITERIA
Publications reporting genotypic susceptibility-testing methods and gyrase gene mutations in M. leprae clinical strains.
RESULTS
In 25 studies meeting our inclusion criteria, 2884 M. leprae isolates were analysed (2236 for gyrA only (77%) and 755 for both gyrA and gyrB (26%)): 3.8% of isolates had gyrA mutations (n = 110), mostly at position 91 (n = 75, 68%) and 0.8% gyrB mutations (n = 6). Since we found discrepancies regarding the location of substitutions associated with FQ resistance, we established a consensus numbering system to properly number the mutations. We also designed a 3D model of the M. leprae DNA gyrase to predict the impact of mutations whose role in FQ-susceptibility has not been demonstrated previously.
CONCLUSIONS
Mutations in DNA gyrase are observed in 4% of the M. leprae clinical isolates. To solve discrepancies among publications and to distinguish between mutations associated with FQ resistance or susceptibility, the consensus numbering system we proposed as well as the 3D model of the M. leprae gyrase for the evaluation of the impact of unknown mutations in FQ resistance, will provide help for resistance surveillance.
Topics: DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Mutation; Mycobacterium leprae
PubMed: 34265461
DOI: 10.1016/j.cmi.2021.07.007 -
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 -
Revista Brasileira de Epidemiologia =... 2021To investigate the risk factors associated with leprosy in contacts of patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the risk factors associated with leprosy in contacts of patients.
METHOD
We carried out a systematic review and meta-analysis by searching the databases MEDLINE, Embase, Cochrane Library, CINAHL, LILACS, Scopus, and Web of Science until September 2019. Four reviewers carried out the selection, analysis, and evaluation of quality of studies. The random effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (95% CI) when heterogeneity was greater than 50%.
RESULTS
The search resulted in 2,148 references and included 24 reports. Most of the studies had been conducted in Brazil and India, had a cohort design and included household, neighbors, and social contacts. The risk factors associated with illness due to leprosy in contacts were: illiteracy (RR = 1,48; 95%CI 1,22 - 1,79), living in the same house (RR = 2,41; 95%CI 1,87 - 3,10) of a case of leprosy with high bacillary load (RR = 2.40; 95%CI 1.69 - 3.41), seropositivity to the Mycobacterium leprae PGL-1 (phenolic glycolipid-1) antigen (RR = 3.54; 95%CI 2.21 - 5.67), presence of the bacillus in the bloodstream (RR = 10.61; 95%CI 4.74 - 23.77) and negative Mitsuda reaction (RR = 2,68; 95%CI 1,76 - 4,07). Immunization with BCG (bacillus Calmette-Guérin) vaccine had a protective effect against leprosy.
CONCLUSION
Leprosy in contacts of patients involves social determination, individual susceptibility, and difficulties in access to disease control actions, but modifiable risk factors are the main determinants of illness in this population.
Topics: Antigens, Bacterial; Brazil; Glycolipids; Humans; Leprosy; Mycobacterium leprae
PubMed: 34231829
DOI: 10.1590/1980-549720210039 -
Medicine May 2022The aim of this study was to evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF (Xpert) for the diagnosis of tuberculous pleurisy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF (Xpert) for the diagnosis of tuberculous pleurisy (TBP) head-to-head using meta-analysis method.
METHODS
On May 12, 2021, we searched multiple databases for reports that used Xpert Ultra and Xpert for TBP diagnosis head-to-head and screened eligible studies for inclusion. Accuracy of Xpert Ultra and Xpert were compared to that of the composite reference standard (CRS) and culture. When heterogeneity was evident, sources of heterogeneity were explored using subgroup analyses, sensitivity analysis, and meta-regression analyses.
RESULTS
Five articles met the inclusion criteria for meta-analysis. When results from different specimens or different reference standards were reported in the same article, we analyzed them as separate studies. Thus, 6 studies compared Xpert Ultra and Xpert with CRS, 5 studies compared Xpert Ultra and Xpert with culture. Pooled sensitivity and specificity of Xpert Ultra were 52% and 98% compared to CRS, and 82% and 77% compared to culture. Pooled sensitivity and specificity of Xpert were 22% and 99% compared to CRS, and 48% and 94% compared to culture. Significant heterogeneity in sensitivity was observed compared to CRS.
CONCLUSION
The sensitivity of Xpert Ultra was moderate but better than that of the Xpert; however, its specificity was lower. The role of Xpert Ultra and Xpert in the early and rapid diagnosis of TBP was limited.
Topics: Antibiotics, Antitubercular; Humans; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 35608435
DOI: 10.1097/MD.0000000000029363 -
BMC Infectious Diseases May 2023Carbapenemase-producing Enterobacteriaceae are by far the most public health and urgent clinical problems with antibiotic resistance. They cause longer hospital stays,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Carbapenemase-producing Enterobacteriaceae are by far the most public health and urgent clinical problems with antibiotic resistance. They cause longer hospital stays, more expensive medical care, and greater mortality rates. This systematic review and meta-analysis aimed to indicate the prevalence of carbapenemase-producing Enterobacteriaceae in Ethiopia.
METHODS
This systematic review and meta-analysis was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Electronic databases like PubMed, Google Scholar, CINAHL, Wiley Online Library, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and the Web of Sciences were used to find relevant articles. In addition, the Joanna Briggs Institute quality appraisal tool was used to assess the quality of the included studies. Stata 14.0 was used for statistical analysis. Heterogeneity was assessed by using Cochran's Q test and I statistics. In addition, publication bias was assessed using a funnel plot and Egger's test. A random effect model was used to estimate the pooled prevalence. Sub-group and sensitivity analysis were also done.
RESULTS
The overall pooled prevalence of carbapenemase-producing Enterobacteriaceae in Ethiopia was 5.44% (95% CI 3.97, 6.92). The prevalence was highest [6.45% (95% CI 3.88, 9.02)] in Central Ethiopia, and lowest [(1.65% (95% CI 0.66, 2.65)] in the Southern Nations and Nationalities People Region. In terms of publication year, 2017-2018 had the highest pooled prevalence [17.44 (95% CI 8.56, 26.32)] and 2015-2016 had the lowest [2.24% (95% CI 0.87, 3.60)].
CONCLUSION
This systematic review and meta-analysis showed a high prevalence of carbapenemase-producing Enterobacteriaceae. So, to alter the routine use of antibiotics, regular drug susceptibility testing, strengthening the infection prevention approach, and additional national surveillance on the profile of carbapenem resistance and their determining genes among Enterobacteriaceae clinical isolates are required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (2022: CRD42022340181).
Topics: Humans; Ethiopia; Carbapenem-Resistant Enterobacteriaceae; Prevalence; Microbial Sensitivity Tests; Mycobacterium tuberculosis
PubMed: 37138285
DOI: 10.1186/s12879-023-08237-5 -
The Journal of Antimicrobial... Feb 2024Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible.
METHOD
Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline's impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans.
RESULTS
Fifty studies met the inclusion criteria: 33 assessed bedaquiline's impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline's efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection.
CONCLUSIONS
Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Diarylquinolines; Anti-Bacterial Agents
PubMed: 38134888
DOI: 10.1093/jac/dkad372 -
Tuberculosis (Edinburgh, Scotland) Jul 2022Tuberculous infection of T cell spot test (T-SPOT.TB) and adenosine deaminase (ADA) have a high diagnostic value in pleural effusion for tuberculous pleurisy. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous infection of T cell spot test (T-SPOT.TB) and adenosine deaminase (ADA) have a high diagnostic value in pleural effusion for tuberculous pleurisy. However, there were major differences in existing research in regard to the clinical application of the two trials. Therefore, we conducted a meta-analysis to systematically evaluate the diagnostic value of T-SPOT.TB and ADA.
METHODS
Pubmed, Web of Science and Embase databases were searched to compare diagnosis of tuberculous pleurisy by T-SPOT.TB and ADA. The search period was from inception to August 31, 2021. Statistical analyses were performed using Meta-disc 1.4, Revman 5.4 and Stata 16.0. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize overall diagnostic performance.
RESULTS
10 qualified original research studies were included, with a total of 2075 patients, of which were 1391 tuberculous pleurisy and 684 non-tuberculous pleurisy. The pooled estimates of diagnostic accuracy of T-SPOT.TB were as follows: sensitivity, 0.88 (95% CI: 0.86-0.90; I = 92.7%); specificity, 0.79 (95% CI: 0.76-0.82; I = 93.7%); PLR, 4.49 (95% CI: 2.29-8.80; I = 94.9%); NLR, 0.15 (95% CI: 0.08-0.30; I = 94.3%), DOR, 35.72 (95% CI: 11.15-114.47; I = 91.5%). The AUC for SROC was 0.9283 (95% CI: 0.8912-0.9654). The pooled estimates of diagnostic accuracy of ADA were as follows: sensitivity, 0.65 (95% CI: 0.62-0.67; I = 98.2%); specificity, 0.90 (95% CI: 0.88-0.92; I = 69.4%); PLR, 6.12 (95% CI: 4.71-7.96; I = 11.9%); NLR, 0.33 (95% CI: 0.12-0.89; I = 99.5%), DOR, 23.18 (95% CI: 12.75-42.14; I = 66.7%). The AUC for SROC was 0.9208 (95% CI: 0.9029-0.9387).
CONCLUSION
Both T-SPOT.TB and ADA had high value in the diagnosis of tuberculous pleurisy. The sensitivity of T-SPOT.TB was higher than ADA, but the specificity of ADA was higher than T-SPOT.TB. On the whole, T-SPOT. TB had similar diagnostic accuracy to ADA.
Topics: Adenosine Deaminase; Humans; Mycobacterium tuberculosis; Pleural Effusion; Pleurisy; Sensitivity and Specificity; T-Lymphocytes; Tuberculosis, Pleural
PubMed: 35777322
DOI: 10.1016/j.tube.2022.102223 -
Tuberkuloz Ve Toraks Dec 2023Non-tuberculous mycobacteria (NTM) can cause diseases not only in individuals with compromised immune systems but also in those with normal immune function. This study...
Non-tuberculous mycobacteria (NTM) can cause diseases not only in individuals with compromised immune systems but also in those with normal immune function. This study aimed to compare the prevalence of NTM in Türkiye and worldwide between 2012 and 2022. This study was designed following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure. A systematic search was conducted between January 2012 and September 2022 using different electronic databases, including Pubmed, Medline, Embase, Web of Science, Ebsco, Scopus, Türk Medline, and Google Scholar. During the literature review process, titles and abstracts were examined and the full texts of the studies were accessed. In 13 research articles from Türkiye included in the study, a total of 17.293 samples were studied and a total of 1304 NTM (7.54%) strains were isolated from these samples. Among the 1304 NTM strains reported from Türkiye, the top three most frequently isolated species were M. abscessus (29.83%), M. lentiflavum (14.97%), M. fortuitum (14.38%). In 35 studies included from around the world, a total of 512.626 samples were studied and a total of 12.631 NTM (2.46%) strains were isolated from these samples. Among the 12631 NTM strains isolated, the top three most frequently isolated species were M. intracellulare (28.13%), M. avium (17.70%) and M. abscessus (14.88%). This study unveiled the global prevalence of NTM-infected patients, detailing species distribution and microbiological diagnostic methods. Variations in NTM spread were observed, influenced by diverse factors.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Prevalence; Turkey
PubMed: 38152011
DOI: 10.5578/tt.20239609 -
International Journal of Infectious... Mar 2022Otomastoiditis caused by Mycobacterium abscessus is rare, but its incidence has increased over the past decades and its optimal treatment remains unknown. This study... (Meta-Analysis)
Meta-Analysis Review
Clinical characteristics and an evaluation of predictors for a favourable outcome of Mycobacterium abscessus otomastoiditis: a systematic review and meta-analysis of individual participant data.
BACKGROUND
Otomastoiditis caused by Mycobacterium abscessus is rare, but its incidence has increased over the past decades and its optimal treatment remains unknown. This study aims to summarise the clinical and therapeutic features and find characteristics of patients with M. abscessus otomastoiditis associated with favourable treatment outcomes.
METHODS
We searched MEDLINE, Embase and Web of Science to identify studies including patients with M. abscessus otomastoiditis. A 1-stage individual patient data (IPD) meta-analysis was conducted. A 2-level mixed-effects linear regression model was provided for antimycobacterial treatment duration.
RESULTS
Twenty-three studies reported a total of 85 patients. Children possess a unique clinical profile including a history of ear infections, tympanostomy tube placement and antibiotic treatment. Antimycobacterial treatment was administered for 26 (interquartile range [IQR]: 15-35) weeks. Macrolides were prescribed in 98.8% of the cases. Surgery was performed in 80.5% of the cases, of which, 47.1% required revision surgery. Otalgia was a significant predictor (β = 9.3; P = .049) of antimycobacterial treatment duration.
CONCLUSIONS
Mastoid surgery (regularly requiring revision) and a multidrug regimen for a minimum of 6 months, including a minimum of 3 active agents, are most often needed to attain cure. The presence of otalgia significantly extends the treatment duration of M. abscessus otomastoiditis.
Topics: Anti-Bacterial Agents; Child; Humans; Macrolides; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 35038600
DOI: 10.1016/j.ijid.2022.01.017 -
Frontiers in Immunology 2022Mendelian susceptibility to mycobacterial disease (MSMD) arises from a group of rare inherited errors of immunity that result in selective susceptibility of otherwise... (Review)
Review
Mendelian susceptibility to mycobacterial disease (MSMD) arises from a group of rare inherited errors of immunity that result in selective susceptibility of otherwise healthy people to clinical disease caused by low virulence strains of mycobacteria, such as Bacille Calmette-Guérin (BCG) and environmental mycobacteria. Patients have normal resistance to other pathogens and no overt abnormalities in routine immunological and hematological evaluations for primary immunodeficiencies. At least 19 genes and 34 clinical phenotypes have been identified in MSMD. However, there have been no systematic reports on the clinical characteristics and genetic backgrounds of MSMD in China. In this review, on the one hand, we summarize an update findings on molecular defects and immunological mechanisms in the field of MSMD research globally. On the other hand, we undertook a systematic review of PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, CNKI, and Wanfang to identify articles published before Jan 23, 2022, to summarize the clinical characteristics, diagnosis, treatment, and prognosis of MSMD in China. All the English and Chinese publications were searched without any restriction on article types.
Topics: Humans; Genetic Predisposition to Disease; Mycobacterium Infections; Mycobacterium bovis; Prognosis; China
PubMed: 36569938
DOI: 10.3389/fimmu.2022.926781