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Microorganisms Mar 2022Beta-lactamase (BL) production is a major public health problem. Although not the most frequent AmpC type, AmpC-BL is increasingly isolated, especially plasmid AmpC-BL...
Beta-lactamase (BL) production is a major public health problem. Although not the most frequent AmpC type, AmpC-BL is increasingly isolated, especially plasmid AmpC-BL (pAmpC-BL). The objective of this study was to review information published to date on pAmpC-BL in and and on the epidemiology and detection methods used by clinical microbiology laboratories, by performing a systematic review using the MEDLINE PubMed database. The predictive capacity of a screening method to detect AmpC-BL using disks with cloxacillin (CLX) was also evaluated by studying 102 clinical isolates grown in CHROMID ESBL medium with the addition of cefepime (FEP), cefoxitin (FOX), ertapenem (ETP), CLX, and oxacillin with CLX. The review, which included 149 publications, suggests that certain risk factors (prolonged hospitalization and previous use of cephalosporins) are associated with infections by pAmpC-BL-producing microorganisms. The worldwide prevalence has increased over the past 10 years, with a positivity rate ranging between 0.1 and 40%, although AmpC was only detected when sought in a targeted manner. CMY-2 type has been the most prevalent pAmpC-BL-producing microorganism. The most frequently used phenotypic method has been the double-disk synergy test (using CLX disks or phenyl-boronic acid and cefotaxime [CTX] and ceftazidime) and the disk method combined with these inhibitors. In regard to screening methods, a 1-µg oxacillin disk with CLX showed 88.9% sensitivity, 100% specificity, 100% positive predictive value (PPV), 98.9% negative predictive value (NPV), and 98.9% validity index (VI). This predictive capacity is reduced with the addition of extended-spectrum beta-lactamases, showing 62.5% sensitivity, 100% specificity, 100% PPV, 93.5% NPV, and 94.1% VI. In conclusion, there has been a worldwide increase in the number of isolates with pAmpC-BL, especially in Asia, with CMY-2 being the most frequently detected pAmpC-BL-producing type of microorganism. Reduction in its spread requires routine screening with a combination of phenotypic methods (with AmpC inhibitors) and genotypic methods (multiplex PCR). In conclusion, the proposed screening technique is an easy-to-apply and inexpensive test for the detection of AmpC-producing isolates in the routine screening of multidrug-resistant microorganisms.
PubMed: 35336186
DOI: 10.3390/microorganisms10030611 -
Access Microbiology 2023In Central Africa, it is difficult to tackle antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies... (Review)
Review
BACKGROUND
In Central Africa, it is difficult to tackle antibiotic resistance, because of a lack of data and information on bacterial resistance, due to the low number of studies carried out in the field. To fill this gap, we carried out a systematic review of the various studies, and devised a molecular epidemiology of antimicrobial resistance from humans, animals and the environmental samples.
METHOD
A systematic search of all publications from 2005 to 2020 on bacterial resistance in Central Africa (Gabon, Cameroon, Democratic Republic of Congo, Central African Republic, Chad, Republic of Congo, Equatorial Guinea, São Tomé and Príncipe, Angola) was performed on Pubmed, Google scholar and African Journals Online (AJOL). All circulating resistance genes, prevalence and genetic carriers of these resistances were collected. The study area was limited to the nine countries of Central Africa.
RESULTS
A total of 517 studies were identified through a literature search, and 60 studies carried out in eight countries were included. Among all articles included, 43 articles were from humans. Our study revealed not only the circulation of beta-lactamase and carbapenemase genes, but also several other types of resistance genes. To finish, we noticed that some studies reported mobile genetic elements such as integrons, transposons, and plasmids.
CONCLUSION
The scarcity of data poses difficulties in the implementation of effective strategies against antibiotic resistance, which requires a health policy in a 'One Health' approach.
PubMed: 37691840
DOI: 10.1099/acmi.0.000556.v5 -
European Journal of Medical Research Jul 2023Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dental pulp stem cells (DPSCs) are adult stem cells with multi-directional differentiation potential derived from ectoderm. Vitro experiments have shown that adding cytokines can help DPSCs to be transformed from multipotent stem cells to osteoblasts. TGF-β has been proved to have an effect on the proliferation and mineralization of bone tissue, but its effect on the osteogenesis and proliferation of dental pulp stem cells is still uncertain. We aim to determine the effect of TGF-β on the osteogenesis and proliferation of dental pulp stem cells.
METHODS
We have identified studies from the Cochrane Central Register of Controlled Trials, PubMed, Embase, and China national knowledge infrastructure (CNKI) for studies interested in TGF-β and proliferation and differentiation of dental pulp stem cells in the following indicators: A490 (an index for evaluating cell proliferation), bone sialoprotein (BSP), Col plasmid-1 (Col-1), osteocalcin (OCN), runt-related transcription factor 2 (Runx-2); and the number of mineralized nodules. Any language restrictions were rejected. Furthermore, we drew a forest plot for each outcome. We conducted a sensitivity analysis, data analysis, heterogeneity, and publication bias test. We evaluate the quality of each study under the guidance of Cochrane's tool for quality assessment.
RESULTS
The pooled data showed that TGF-β could promote the proliferation and ossification of dental pulp stem cells. All the included results support this conclusion except for the number of mineralized nodules: TGF-β increases the A490 index (SMD 3.11, 95% CI [0.54-5.69]), promotes the production of BSP (SMD 3.11, 95% CI [0.81-6.77]), promotes the expression of Col-1 (SMD 4.71, 95% CI [1.25-8.16]) and Runx-2 (SMD 3.37, 95% CI [- 0.63 to 7.36]), increases the content of OCN (SMD 4.32, 95% CI [1.20-7.44]) in dental pulp, and has no significant effect on the number of mineralized nodules (SMD 3.87, 95% CI [- 1.76 to 9.51]) in dental pulp stem cells.
CONCLUSIONS
TGF-β promotes the proliferation and osteogenesis of dental pulp stem cells.
Topics: Humans; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Osteogenesis; Stem Cells; Transforming Growth Factor beta
PubMed: 37501191
DOI: 10.1186/s40001-023-01227-y -
Scientific Reports Apr 2022The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the... (Meta-Analysis)
Meta-Analysis
The comprehensive effect size of several commercial vaccines and vaccine candidates against edema disease (ED) has not been evaluated to date. To integrate the effectiveness of ED vaccines reported so far and to compare and evaluate the posterior-effect estimates of each vaccine type with network models, we identified eligible studies (n = 12) from the electronic databases using specified search strings. Data for dichotomous outcomes (i.e., mortality and clinical symptoms) and continuous outcomes (i.e., fecal shedding and average daily gain) were extracted and analyzed. Conventional meta-analysis shows that, compared with that in non-vaccinated pigs, vaccinated animals are likely to show reduced mortality (OR = 0.07) and clinical signs of ED (OR = 0.11), and increased productivity (SMD = 0.73). Although reduced fecal shedding (SMD = - 1.29) was observed in vaccinated pigs, this could not be fully determined on insufficient grounds. In contrast to mortality and clinical symptoms, fecal shedding (I = 88%) and average daily gain (I = 85%) showed immense heterogeneity, which was attributed to the small sample size and vaccination route, respectively. According to the Bayesian network meta-analysis, the plasmid-based DNA vaccine demonstrated a better effect for all outcomes compared to other types of vaccines. However, these findings should be carefully interpreted with consideration to potential mediators, insufficient data, and inconsistent network models.
Topics: Animals; Bayes Theorem; Edema; Edema Disease of Swine; Escherichia coli Infections; Network Meta-Analysis; Shiga-Toxigenic Escherichia coli; Swine; Vaccine Efficacy
PubMed: 35440612
DOI: 10.1038/s41598-022-10439-x -
Infection and Drug Resistance 2022Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can... (Review)
Review
Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can be encoded by plasmid or chromosomal-mediated genes. The major issues associated with carbapenemases-producing organisms are compromising the activity and increasing the resistance to carbapenems which are the last resort antibiotics used in treating serious infections. The global increase of pathogen, carbapenem-resistant has significantly threatened public health. Thus, there is a pressing need for a better understanding of this pathogen, to know the various carbapenem resistance encoding genes and dissemination of resistance genes from which help in developing strategies to overcome this problem. The horizontal transfer of resistant determinants through mobile genetic elements increases the incidence of multidrug, extensive drug, and Pan-drug resistant . Therefore, the current review aims to know the various mechanisms of carbapenem resistance, categorize and discuss carbapenemases encoding genes and various mobile genetic elements, and the prevalence of carbapenemase genes in recent years in from various geographical regions.
PubMed: 36579124
DOI: 10.2147/IDR.S386641 -
Germs Dec 2020Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa. (Review)
Review
INTRODUCTION
Updated and comprehensive data on the mechanism underlying colistin resistance is lacking in Africa.
LITERATURE SEARCH
Herein, we aimed to review available literature on the molecular mechanisms of colistin resistance in Africa. PubMed, Google Scholar, and African Journal online databases were searched on the 15th of January 2020 for original research articles that reported mechanisms of colistin resistance in any of the 54 African countries.
REVIEW
Of the 1473 studies identified through initial database search, 36 met the inclusion criteria. Colistin resistance was mostly observed in isolated from human clinical samples. Plasmid-mediated colistin resistance mechanism (26; 72.2%) was the most frequently reported resistance mechanism. About three-quarters (27; 75.0%) of the 36 studies were done in North Africa. In this zone, the mobilized colistin resistance () genes were mostly detected in harboring three plasmid types, , , and , from animal samples (n=9; 42.8%). Of the six studies performed in Southern Africa, four reported mostly detected from human samples (n=2; 50.0%) in isolates carrying , , and with diverse range of STs. One hitherto unknown mutation, the mutation in the gene was detected in colistin resistant isolates in this region, which was absent in colistin susceptible isolates. In West and Central Africa, two and one studies, respectively, reported gene exclusively in isolates.
CONCLUSIONS
Transferable plasmid mediated colistin resistance is rapidly emerging in Africa with as the predominant genetic variant in human, animals, and environmental samples.
PubMed: 33489952
DOI: 10.18683/germs.2020.1229 -
Infection and Drug Resistance 2024The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been... (Review)
Review
BACKGROUND
The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment.
OBJECTIVE
This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa.
RESULTS
A total of 137 research articles collected from 2009 to 2023 were selected for this review, including articles reporting carbapenem-resistant bacteria in animals (81/137; 59.1%), the environment (66/137; 48.2%), and foods (26/137; 19%). Carbapenem-resistant bacterial species belonged to 31 genera and 17 families, including mainly spp. (68/127; 53.5%); spp. (45/127; 35.4%); spp. (20/127; 15.7%), spp. (19/127; 15%) and spp. (15/127; 11.8%). The prevalence of CRBs by country ranged from 1.1% to 48.5%, and the pooled prevalence of CRBs isolated from animal-environment-food in Africa was 19.1% (2804/14,684; Standard Deviation = 15). Twenty carbapenemase families belonging to A, B, C, and D Ambler classes were reported, including mainly carbapenemase genes from (44/84; 52.4%), (34/84; 40.5%), (23/84; 27.4%), (22/84; 26.2%), (19/84; 22.6%), and (12/84; 14.3%) families. The reported mobile genetic elements (MGE) carrying carbapenemase-encoding genes included plasmids (16/19; 84.2%), integrons (3/19; 15.8%), transposons (3/19; 15.8%), and insertion sequences (2/19; 10.5%). was often carried by (60kb-65kb) IncL/M-type pOXA-48 plasmids, while was often carried by (45-50kb) IncX-type plasmids. Moreover, 25 articles investigated and reported virulent and hypervirulent CRBs that carried multiple virulence factors.
CONCLUSION
Animal-environment-food ecosystems would constitute reservoirs of CRBs involved in human infections. The One Health approach and constant collaboration between governments are necessary to drastically reduce the mortality rates linked to antimicrobial resistance.
PubMed: 38715963
DOI: 10.2147/IDR.S458317 -
Applied and Environmental Microbiology Feb 2023Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very...
Site-specific recombinases (integrases) can mediate the horizontal transfer of genomic islands. The ability to integrate large DNA sequences into target sites is very important for genetic engineering in prokaryotic and eukaryotic cells. Here, we characterized an unprecedented catalogue of 530 tyrosine-type integrases by examining genes potentially encoding tyrosine integrases in bacterial genomic islands. The phylogeny of putative tyrosine integrases revealed that these integrases form an evolutionary clade that is distinct from those already known and are affiliated with novel integrase groups. We systematically searched for candidate integrase genes, and their integration activities were validated in a bacterial model. We verified the integration functions of six representative novel integrases by using a two-plasmid integration system consisting of a donor plasmid carrying the integrase gene and site and a recipient plasmid harboring an site in -deficient Escherichia coli. Further quantitative reverse transcription-PCR (qRT-PCR) assays validated that the six selected integrases can be expressed with their native promoters in E. coli. The region reductions showed that the extent of sites of integrases is approximately 200 bp for integration capacity. In addition, mutational analysis showed that the conserved tyrosine at the C terminus is essential for catalysis, confirming that these candidate proteins belong to the tyrosine-type recombinase superfamily, i.e., tyrosine integrases. This study revealed that the novel integrases from bacterial genomic islands have site-specific recombination functions, which is of physiological significance for their genomic islands in bacterial chromosomes. More importantly, our discovery expands the toolbox for genetic engineering, especially for efficient integration activity. Site-specific recombinases or integrases have high specificity for DNA large fragment integration, which is urgently needed for gene editing. However, known integrases are not sufficient for meeting multiple integrations. In this work, we discovered an array of integrases through bioinformatics analysis in bacterial genomes. Phylogeny and functional assays revealed that these new integrases belong to tyrosine-type integrases and have the ability to conduct site-specific recombination. Moreover, region extent and catalysis site analysis were characterized. Our study provides the methodology for discovery of novel integrases and increases the capacity of weapon pool for genetic engineering in bacteria.
Topics: Integrases; Genomic Islands; Escherichia coli; Tyrosine; Plasmids; Bacteriophages; Attachment Sites, Microbiological
PubMed: 36719242
DOI: 10.1128/aem.01738-22 -
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 -
MSystems Nov 2020Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited...
Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited molecular diagnostics, expensive therapeutics, inadequate numbers of skilled clinicians and scientists, and unsanitary environments. The epidemiology of Gram-negative bacteria, their AR genes, and geographical distribution in Africa are described here. Data were extracted and analyzed from English-language articles published between 2015 and December 2019. The genomes and AR genes of the various species, obtained from the Pathosystems Resource Integration Center (PATRIC) and NCBI were analyzed phylogenetically using Randomized Axelerated Maximum Likelihood (RAxML) and annotated with Figtree. The geographic location of resistant clones/clades was mapped manually. Thirty species from 31 countries and 24 genera from 41 countries were analyzed from 146 articles and 3,028 genomes, respectively. Genes mediating resistance to β-lactams (including , , , , , and ), fluoroquinolones (, , , and mutations, etc.), aminoglycosides (including and ), sulfonamides (), trimethoprim (), tetracycline [(A/B/C/D/G/O/M/39)], colistin (), phenicols (, ), and fosfomycin () were mostly found in spp. and , and also in , , , , , etc., on mostly IncF-type, IncX, ColRNAI, and IncR plasmids, within 1 gene cassettes, insertion sequences, and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species and countries and between humans, animals, plants, and the environment were observed; ST103, ST101, ST1/2, and ST69/515 were common strains. Most pathogens were of human origin, and zoonotic transmissions were relatively limited. Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. , , , , , spp., , , , etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend spp. or as better sentinel species for AR surveillance.
PubMed: 33234606
DOI: 10.1128/mSystems.00897-20