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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 -
Annals of the New York Academy of... Oct 2021In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating... (Meta-Analysis)
Meta-Analysis
Risk factors for, and molecular epidemiology and clinical outcomes of, carbapenem- and polymyxin-resistant Gram-negative bacterial infections in pregnant women, infants, and toddlers: a systematic review and meta-analyses.
In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne bla , bla , bla , bla bla , bla , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Carbapenems; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacterial Infections; Humans; Infant; Infant, Newborn; Middle Aged; Molecular Epidemiology; Mortality; Polymyxins; Pregnancy; Pregnancy Complications, Infectious; Risk Assessment; Risk Factors; Young Adult
PubMed: 34212401
DOI: 10.1111/nyas.14650 -
International Journal of Antimicrobial... Jan 2021Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health'...
Epidemiology and prevalence of extended-spectrum β-lactamase- and carbapenemase-producing Enterobacteriaceae in humans, animals and the environment in West and Central Africa.
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are widespread. Here we used the 'One Health' approach to determine knowledge gaps on ESBL-E and CPE in West and Central Africa. We searched all articles on ESBL-E and CPE in these African regions published in PubMed, African Journals Online and Google Scholar from 2000 onwards. Among the 1201 articles retrieved, we selected 165 studies (West Africa, 118; Central Africa, 47) with data from 22 of the 26 West and Central Africa countries. Regarding the settings, 136 articles focused only on humans (carriage and/or infection), 6 articles on humans and animals, 13 on animals, 1 on humans and the environment, 8 on the environment and 1 on humans, animals and environments. ESBL-E prevalence ranged from 11-72% in humans and 7-79% in aquatic environments (wastewater). In animals, ESBL-E prevalence hugely varied: 0% in cattle, 11-36% in chickens, 20% in rats, 21-71% in pigs and 32-75% in dogs. The bla gene was the predominant ESBL-encoding gene and was associated with plasmids of incompatibility groups F, H, K, Y, N, I1 and R. CPE were studied only in humans. Class B metallo-β-lactamases (NDM) and class D oxacillinases (OXA-48 and OXA-181) were the most common carbapenemases. Our results show major knowledge gaps, particularly on ESBL and CPE in animals and the environment, that might limit antimicrobial resistance management in these regions. The results also emphasise the urgent need to improve active surveillance programmes in each country and to support antimicrobial stewardship.
Topics: Africa, Central; Africa, Western; Animals; Anti-Bacterial Agents; Bacterial Proteins; Cattle; Chickens; Dogs; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Environmental Microbiology; Humans; Plasmids; Prevalence; Rats; Swine; beta-Lactamases
PubMed: 33075511
DOI: 10.1016/j.ijantimicag.2020.106203 -
Annals of the New York Academy of... Mar 2022Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant... (Meta-Analysis)
Meta-Analysis
Antimicrobial resistance (AMR) is a public health threat globally. Carbapenems are β-lactam antibiotics used as last-resort agents for treating antibiotic-resistant infections. Mobile genetic elements (MGEs) play an important role in the dissemination and expression of antimicrobial resistance genes (ARGs), including the mobilization of ARGs within and between species. The presence of MGEs around carbapenem-hydrolyzing enzymes, called carbapenemases, in bacterial isolates in Africa is concerning. The association between MGEs and carbapenemases is described herein. Specific plasmid replicons, integrons, transposons, and insertion sequences were found flanking specific and different carbapenemases across the same and different clones and species isolated from humans, animals, and the environment. Notably, similar genetic contexts have been reported in non-African countries, supporting the importance of MGEs in driving the intra- and interclonal and species transmission of carbapenemases in Africa and globally. Technical and budgetary limitations remain challenges for epidemiological analysis of carbapenemases in Africa, as studies undertaken with whole-genome sequencing remained relatively few. Characterization of MGEs in antibiotic-resistant infections can deepen our understanding of carbapenemase epidemiology and facilitate the control of AMR in Africa. Investment in genomic epidemiology will facilitate faster clinical interventions and containment of outbreaks.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Carbapenems; Humans; One Health; Plasmids; beta-Lactamases
PubMed: 34753206
DOI: 10.1111/nyas.14703 -
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 -
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 -
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 -
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