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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 -
MicrobiologyOpen Apr 2019Resistance to colistin, mediated by chromosomal mutations and more recently, by plasmid-borne mcr genes, is increasingly being reported in bacterial isolates taken from...
Resistance to colistin, mediated by chromosomal mutations and more recently, by plasmid-borne mcr genes, is increasingly being reported in bacterial isolates taken from humans, animals, farms, foods, and the environment. To easily identify and contain this quickly spreading menace, efficient diagnostics that are cheaper, faster, simpler, sensitive, and specific have become indispensable and urgently necessary. A thorough and systematic review of the literature available at Pubmed, ScienceDirect and Web of Science was thus undertaken to identify articles describing novel and efficient colistin resistance- and mcr gene-detecting methods. From the final 23 studies included in this review, both phenotypic and molecular tests were found. The phenotypic tests consisted of novel culture media viz., SuperPolymyxin™, CHROMagar COL-APSE and LBJMR media, commercial automated MIC-determining instruments such as MICRONAUT-S, Vitek 2, BD Phoenix, Sensititre and MicroScan, and novel assays such as Colistin MAC test, Colispot, rapid polymxin NP test (RPNP), alteration of Zeta potential, modified RPNP test, MICRONAUT-MIC Strip, MIC Test Strip, UMIC System, and Sensitest™ Colistin. Molecular diagnostics consisted of the CT103XL microarray, eazyplex SuperBug kit, and Taqman /SYBR Green real-time PCR assays, with 100% sensitivity and specificity plus a shorter turnaround time (<3 hr). Based on the sensitivity, specificity, cost, required skill and turnaround time, the RPNP test and/or novel culture media is recommended for under-resourced laboratories while the Multiplex PCR or Taqman /SYBR Green real-time PCR assay alongside the RPNP or novel culture media is suggested for well-resourced ones.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Genetic Techniques; Humans; Microbial Sensitivity Tests
PubMed: 29974640
DOI: 10.1002/mbo3.682 -
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 -
The Journal of Antimicrobial... Mar 2019Recent reports indicate the emergence of a new carbapenemase-producing Klebsiella pneumoniae clone, ST307. We sought to better understand the global epidemiology and...
OBJECTIVES
Recent reports indicate the emergence of a new carbapenemase-producing Klebsiella pneumoniae clone, ST307. We sought to better understand the global epidemiology and evolution of this clone and evaluate its association with antimicrobial resistance (AMR) genes.
METHODS
We collated information from the literature and public databases and performed a comparative analysis of 95 ST307 genomes (including 37 that were newly sequenced).
RESULTS
We show that ST307 emerged in the mid-1990s (nearly 20 years prior to its first report), is already globally distributed and is intimately associated with a conserved plasmid harbouring the blaCTX-M-15 ESBL gene and several other AMR determinants.
CONCLUSIONS
Our findings support the need for enhanced surveillance of this widespread ESBL clone in which carbapenem resistance has occasionally emerged.
Topics: Carbapenem-Resistant Enterobacteriaceae; Drug Resistance, Bacterial; Genome, Bacterial; Genotype; Global Health; Humans; Klebsiella Infections; Klebsiella pneumoniae; Molecular Epidemiology; beta-Lactamases
PubMed: 30517666
DOI: 10.1093/jac/dky492 -
Journal of Hazardous Materials Mar 2022Antibiotic resistance is considered one of the biggest threats to public health and has become a major concern for governments and international organizations. Combating...
Antibiotic resistance is considered one of the biggest threats to public health and has become a major concern for governments and international organizations. Combating this problem starts with improving global surveillance of antibiotic resistance genes (ARGs) and applying standardized protocols, both in a clinical and environmental context, in agreement with the One Health approach. Exceptional efforts should be directed to controlling ARGs conferring resistance to Critically Important Antimicrobials (CIA). In this study, a systematic literature review to synthesize data on the identification of mcr genes using a PCR technique was performed. Additionally, a novel set of PCR primers for mcr-1 - mcr-9 genes detection was proposed. The developed primers were in silico and experimentally validated by comparison with mcr-specific PCR primers reported in the literature. This validation, besides being a proof-of-concept for primers' usefulness, provided insight into the distribution of mcr genes in municipal wastewater, clay and river sediments, glacier moraine, manure, seagulls and auks feces and daphnids from four countries. This analysis proved that commonly used primers may deliver false results, and some mcr genes may be overlooked in tested samples. Newly-developed PCR primers turned out to be relevant for the screening of mcr genes in various environments.
Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Plasmids; Polymerase Chain Reaction
PubMed: 34883371
DOI: 10.1016/j.jhazmat.2021.127936 -
Antimicrobial Resistance and Infection... Jan 2022Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this continent, bacterial contamination of commonly used herbal medicine (HM) is on the increase, but information about antimicrobial resistance in these contaminants is limited due to fragmented studies. Here, we analyzed research that characterized ABR in pathogenic bacteria isolated from HM in Africa since 2000; to generate a comprehensive understanding of the drug-resistant bacterial contamination burden in this region.
METHODS
The study was conducted according to standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We searched for articles from 12 databases. These were: PubMed, Science Direct, Scifinder scholar, Google scholar, HerbMed, Medline, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Commonwealth Agricultural Bureau Abstracts, African Journal Online, and Biological Abstracts. Prevalence and ABR traits of bacterial isolates, Cochran's Q test, and the I statistic for heterogeneity were evaluated using MedCalcs software. A random-effects model was used to determine the pooled prevalence of ABR traits. The potential sources of heterogeneity were examined through sensitivity analysis, subgroup analysis, and meta-regression at a 95% level of significance.
FINDINGS
Eighteen studies met our inclusion criteria. The pooled prevalence of bacterial resistance to at least one conventional drug was 86.51% (95% CI = 61.247-99.357%). The studies were highly heterogeneous (I = 99.17%; p < 0.0001), with no evidence of publication bias. The most prevalent multidrug-resistant species was Escherichia coli (24.0%). The most highly resisted drug was Ceftazidime with a pooled prevalence of 95.10% (95% CI = 78.51-99.87%), while the drug-class was 3 generation cephalosporins; 91.64% (95% CI = 78.64-96.73%). None of the eligible studies tested isolates for Carbapenem resistance. Extended Spectrum β-lactamase genes were detected in 89 (37.2%) isolates, mostly Salmonella spp., Proteus vulgaris, and K. pneumonia. Resistance plasmids were found in 6 (5.8%) isolates; the heaviest plasmid weighed 23,130 Kilobases, and Proteus vulgaris harbored the majority (n = 5; 83.3%).
CONCLUSIONS
Herbal medicines in Africa harbor bacterial contaminants which are highly resistant to conventional medicines. This points to a potential treatment failure when these contaminants are involved in diseases causation. More research on this subject is recommended, to fill the evidence gaps and support the formation of collaborative quality control mechanisms for the herbal medicine industry in Africa.
Topics: Africa; Anti-Bacterial Agents; Bacteria; Drug Contamination; Drug Resistance, Bacterial; Food Contamination; Herbal Medicine
PubMed: 35063036
DOI: 10.1186/s13756-022-01054-6 -
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 -
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