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Panminerva Medica Mar 2022Since December 2019, there has been an outbreak of a novel beta-Coronavirus (SARS-CoV-2) in Wuhan, China. On March 11, 2020, the World Health Organization (WHO) declared...
INTRODUCTION
Since December 2019, there has been an outbreak of a novel beta-Coronavirus (SARS-CoV-2) in Wuhan, China. On March 11, 2020, the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global Coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review was to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans.
EVIDENCE ACQUISITION
After a-priori protocol registration with PROSPERO (181483), systematic research of the published literature was conducted on April 24, 2020, using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database to identify relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA Guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included.
EVIDENCE SYNTHESIS
Our search identified 1359 published papers, 478 preprint articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine.
CONCLUSIONS
This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.
Topics: Animals; BCG Vaccine; COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Humans; SARS-CoV-2; Vaccines, Synthetic; mRNA Vaccines
PubMed: 32456404
DOI: 10.23736/S0031-0808.20.03958-0 -
Nutrients Apr 2020For millennia, naturopaths and physicians have used (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia.... (Meta-Analysis)
Meta-Analysis Review
For millennia, naturopaths and physicians have used (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of , or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of aqueous extracts of polysaccharides and triterpenes in mice exposed to -rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of β-glucan of aqueous extract of , nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.
Topics: Animals; Drugs, Chinese Herbal; Fungal Polysaccharides; Humans; In Vitro Techniques; Mice; Phytotherapy; Radiation Injuries; Radiation-Protective Agents; Reishi; Triterpenes
PubMed: 32325828
DOI: 10.3390/nu12041143 -
JAMA Internal Medicine Apr 2020Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with... (Meta-Analysis)
Meta-Analysis
Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms: A Systematic Review and Meta-analysis.
IMPORTANCE
Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with multidrug-resistant microorganisms (MDROs) is unclear.
OBJECTIVES
To systematically examine the association of use of acid suppressants with the risk of colonization with MDROs and to perform a meta-analysis of current evidence.
DATA SOURCES
PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from database inception through July 8, 2019.
STUDY SELECTION
Study selection was performed independently by 2 authors (R.P.J.W. and C.M.J.E.V.-G.) on the basis of predefined selection criteria; conflicts were resolved by consensus or by an adjudicator (K.v.D.). Human observational studies (case control, cohort, and cross-sectional) and clinical trial designs were selected if they quantified the risk of MDRO colonization in users of acid suppressants in comparison with nonusers.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. Data were extracted independently by the same 2 authors, and adjudication was conducted when necessary. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were estimated using random-effects models; heterogeneity was evaluated using the I2 method.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was intestinal colonization with MDROs of the Enterobacterales order (producing extended-spectrum β-lactamases, carbapenemases, or plasmid-mediated AmpC β-lactamases), vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species.
RESULTS
A total of 26 observational studies including 29 382 patients (11 439 [38.9%] acid suppressant users) met the selection criteria. Primary meta-analysis of 12 studies including 22 305 patients that provided adjusted ORs showed that acid suppression increased the odds of intestinal carriage of MDROs of the Enterobacterales order and of vancomycin-resistant enterococci by roughly 75% (OR = 1.74; 95% CI, 1.40-2.16; I2 = 68%). The odds were concordant with the secondary pooled analysis of all 26 studies (OR = 1.70; 95% CI, 1.44-1.99; I2 = 54%). Heterogeneity was partially explained by variations in study setting and the type of acid suppression.
CONCLUSIONS AND RELEVANCE
Acid suppression is associated with increased odds of MDRO colonization. Notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. In view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent MDRO colonization.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Gastrointestinal Microbiome; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Risk; Vancomycin-Resistant Enterococci
PubMed: 32091544
DOI: 10.1001/jamainternmed.2020.0009 -
Molecular Biology Reports Feb 2020The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these...
The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these genes in Latin American countries, where the prescription of fluoroquinolones is high, has been described in several studies; however, no review of the impact of PMQR in this continent has been conducted. This review summarized current knowledge about the circulation of PMQR among Enterobacteriales in Latin American. After the search and selection, 61 articles were included in the study. Most of studies reported PMQR genes among Enterobacteriales from human (47/61, 77%) and animal (18/61, 29.5%) samples, recovered mainly in Brazil (23/61, 37.7%), Mexico (11/61, 18%), and Uruguay (7/61, 11.5%). Nine different PMQR genes (qnrA, qnrB, qnrS, qnrD, qnrE, aac-(6')-Ib-cr, oqxA, oqxB, and qepA) were found in Latin America, with aac (6')-Ib-cr (37/61, 60.6%) and qnrB (26/61, 42.6%) being the most frequently reported. Escherichia coli (40/61, 65.6%) was the species most frequently reported to carry a PMQR gene, followed by Klebsiella pneumoniae (24/61, 39.3%), Enterobacter cloacae (15/61, 24.6%), and Salmonella spp. (14/61, 22.9%). Thus, this review provides important information which might help in designing measures to control the spread of quinolone resistance determinants on this continent.
Topics: Drug Resistance, Bacterial; Enterobacteriaceae; Geography; Humans; Latin America; Plasmids; Quinolones
PubMed: 31813128
DOI: 10.1007/s11033-019-05220-9 -
Microbial Pathogenesis Feb 2020Efflux of antibiotics is an effective resistance mechanism among antibiotic-resistant Staphylococcus aureus. This systematic review aims to evaluate the frequency and...
BACKGROUND
Efflux of antibiotics is an effective resistance mechanism among antibiotic-resistant Staphylococcus aureus. This systematic review aims to evaluate the frequency and expression of efflux pump genes in S.aureus around the world.
METHOD
A comprehensive literature search of several databases (Medline Pub Med, ISI, Scopus, Google Scholar, ISC, Science direct and Persian Journals Online, and citation lists) was performed. We considered published studies from 2001 to 2018. Articles reporting the prevalence and expression of efflux pump genes were selected.
RESULT
Among 183 articles, 36 studies were selected. Of the 36, 23 articles were conducted in Asia.6 in Europe, 5 in America and 2 in African countries. In most of these studies norA, norB, qacA/B genes were commonly evaluated by molecular methods. The presence of efflux pump genes such as norA, norB, norC, mepA, mdeA, qacA/B was detected by PCR in 21 studies and over-expression of genes were reported in 13 studies. The most frequently reported genes in Asia were norA (75%), norB (60%), mepA (35%), mdeA (33%) and qacA/B (20.8%). In European studies, the prevalence of norB was mostly reported among S.aureus isolates and norA and qacA/B were commonly found in similar studies in America. The investigation of gene expression patterns showed that norA was most frequent single-pattern in Asia and America, norB or mdeA in Europe.
CONCLUSION
According to this study MDR efflux pumps not only cause high-level resistance but also it considerably associated with over-expression of these genes. Due to the selective pressure on MRSA isolate, the enormous diversity of plasmid-encoded genes had been recorded in different regions, owing to the various numbers and types of isolates in each study or types of disinfectants for general use.
Topics: Africa; Anti-Bacterial Agents; Asia; Bacterial Proteins; Databases, Factual; Drug Resistance, Multiple, Bacterial; Europe; Gene Expression Regulation, Bacterial; Membrane Transport Proteins; Multidrug Resistance-Associated Proteins; Plasmids; Staphylococcus aureus; United States
PubMed: 31706002
DOI: 10.1016/j.micpath.2019.103850 -
Travel Medicine and Infectious Disease 2019A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched... (Review)
Review
A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched for articles reporting plasmid-mediated colistin resistance between bacteria isolated from countries of Latin America and the Caribbean. Abstract books of scientific events realized in each region were also examined. After search and selection, 48 studies that included 18,705 isolates recovered between 2000 and 2018 were evaluated. The overall frequency of mcr genes in Latin America was 2.9% (550/18,705), with IncX4 plasmids shown to be the key vectors responsible for the dissemination of genes within the continent. Brazil, Bolivia and Argentina were the countries with the highest number of mcr-positive isolates, and only Colombia (mcr-5) and Brazil (mcr-3) presented mcr genes other than type 1. Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhimurium were mainly found to carry the gene within the continent and these microorganisms showed high susceptibility to ertapenem, meropenem, piperacillin/tazobactam, fosfomycin and tigecycline. This review showed that the mcr gene is circulating in several countries of Latin America. Thus, it is important to encourage microbiological and molecular surveillance programs to avoid the spread of these genes within and outside the continent.
Topics: Bacteria; Caribbean Region; Colistin; Drug Resistance, Bacterial; Genes, Bacterial; Latin America; Plasmids
PubMed: 31336179
DOI: 10.1016/j.tmaid.2019.07.015 -
Environmental Pollution (Barking, Essex... Sep 2019AmpC beta-lactamase genes are some of the most common antibiotic resistance genes and require special attention once they have become mobilised. The detection of these...
AmpC beta-lactamase genes are some of the most common antibiotic resistance genes and require special attention once they have become mobilised. The detection of these genes is well documented in clinical settings. However, there is insufficient knowledge of both plasmid and genomic AmpC genes in aquatic environments. This systematic review aimed to determine the extent of the knowledge gap in the literature regarding the prevalence of AmpC beta-lactamase genes in aquatic systems. Using selected criteria, a total of 27 databases were searched for applicable peer-reviewed journal articles. No date and language restrictions were applied. Journal articles that highlighted the detection of AmpC beta-lactamase genes in environmental aquatic systems, including wastewater treatment plants, were included. Of the 950 literature sources that were identified, 50 were selected for full text analysis based on predetermined criteria. Studies on AmpC genes detection were traced in 23 countries. These studies focused on surface water (24), wastewater (17), sea water (4) and both surface and wastewater (5). Most studies did not specifically aim to detect AmpC genes, but to detect antibiotic resistance genes in general. Presently no surveillance protocols, standardised detection methods or environmental limits exist for these genes and, due to a paucity of research in this field, it is unlikely that such systems will be implemented in the near future. The implications and dynamics of AmpC genes in aquatic systems remain unclear and require intense research to ensure the sustainability of environmental systems and human health.
Topics: Bacterial Proteins; Drug Resistance, Bacterial; Fresh Water; Genes, Bacterial; Humans; Plasmids; Seawater; Wastewater; beta-Lactamases
PubMed: 31284205
DOI: 10.1016/j.envpol.2019.06.106 -
Nature Communications Jun 2019Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and...
Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Bacterial Proteins; Catheter-Related Infections; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Humans; Mice; Plasmids; Pneumonia, Bacterial; Proteomics; Retrospective Studies; Type VI Secretion Systems; Urinary Catheters; Urinary Tract; Urinary Tract Infections; Virulence; Virulence Factors
PubMed: 31235751
DOI: 10.1038/s41467-019-10706-y -
The Indian Journal of Medical Research Feb 2019The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported....
BACKGROUND & OBJECTIVES
The temporal trends in the development of antimicrobial resistance (AMR) among Salmonella Typhi and Salmonella Paratyphi in India have not been systematically reported. We aimed to systematically review the temporal AMR trends (phenotypic and molecular mechanisms) in bacterial isolates from patients with enteric fever over two decades in India.
METHODS
To identify trends in AMR in India, resistance patterns among 4611 individual S. Typhi isolates and 800 S. Paratyphi A isolates, reported from 1992 to 2017 in 40 publications, were analysed. Molecular resistance determinants were extracted from 22 publications and also reviewed in accordance with the PRISMA guidelines. Articles were sourced using a predefined search strategy from different databases.
RESULTS
The analyses suggested that multidrug-resistant (MDR) enteric fever was declining in India and being replaced by fluoroquinolone (FQ) resistance. Mutations in gyrA and parC were key mechanisms responsible for FQ resistance, whereas MDR was largely driven by resistance determinants encoded on mobile genetic elements (plasmids, transposons).
INTERPRETATION & CONCLUSIONS
The results reflect the effect of antimicrobial pressure which has been driving AMR in typhoidal Salmonella in India. Understanding these trends is important in planning future approaches to therapy, which serve as a baseline for assessment of the impact of new typhoid conjugate vaccines against these resistant organisms.
Topics: Anti-Bacterial Agents; Ciprofloxacin; Drug Resistance, Bacterial; Fluoroquinolones; Humans; India; Microbial Sensitivity Tests; Paratyphoid Fever; Salmonella paratyphi A; Salmonella typhi
PubMed: 31219079
DOI: 10.4103/ijmr.IJMR_830_18 -
Microbial Drug Resistance (Larchmont,... Mar 2020Carbapenem-resistant (CRAB) is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. An understanding of the...
Carbapenem-resistant (CRAB) is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. An understanding of the epidemiology of CRAB and the mechanisms of resistance to carbapenems is necessary to develop strategies to curtail their spread. Electronic databases were searched from January 1995 to December 2017 for all studies, which: (1) provide data on the frequency and antibiotic resistance profile of the isolated and (2) describe the mechanisms of carbapenem resistance in detail. Sixty-eight studies were found referring to mechanisms of carbapenem resistance in clinical isolates of , and 56 studies were found referring to the frequency of CRAB. The pooled frequency of carbapenem resistance was 85.1% (95% confidence interval [CI]: 82.2-88.1) in 8,067 clinical isolates of . Resistances due to (55.3%), (41.4%), and (5.2%) genes were the most prevalent reported mechanisms of resistance to carbapenem, respectively. Our data warn that CRAB will rise if the current situation remains uncontrolled. Better control infection strategies and antibiotic managements, particularly in the health care systems, are needed to limit the spread of this pathogen.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Cross-Sectional Studies; Gene Expression; Humans; Iran; Microbial Sensitivity Tests; Plasmids; Prevalence; beta-Lactam Resistance; beta-Lactamases
PubMed: 30822197
DOI: 10.1089/mdr.2018.0435