scholarly journals 1641. Treatment of Recurrent Clostridium difficile Infection With SER-109 Reduces Gastrointestinal Carriage of Antimicrobial Resistance Genes

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S46-S47 ◽  
Author(s):  
Christopher Ford ◽  
Matthew Henn ◽  
Jessica Bryant ◽  
Liyang Diao ◽  
Jennifer Wortman ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Fixed Dose ◽  
Resistant Bacteria ◽  
Recurrent Clostridium Difficile Infection ◽  
Antimicrobial Resistance Genes ◽  
Antibiotic Drug ◽  
The Impact

Abstract Background A healthy gut microbiome is associated with colonization resistance against C. difficile and other pathogens, including bacteria carrying antibiotic resistance genes (AbRG). Designed to facilitate microbiome restoration and reduce the risk of recurrent C. difficile infection (rCDI), SER-109, an investigational microbiome therapeutic, is an ecology of bacterial spores purified from stool from healthy screened donors. We evaluated the impact of engraftment of SER-109 dose species on the abundance of AbRG in rCDI subjects. Methods We generated whole metagenomic shotgun (WMS) data for a subset of study subjects with available stool samples receiving SER-109 (n = 66) or placebo (n = 25) from 2 clinical trials (a dose-ranging Phase 1b study and a fixed-dose Phase 2 trial). WMS data from stool was analyzed to (1) quantify the abundance of AbRG (Comprehensive Antibiotic Resistance Database CARD v.1.1.8) and (2) define subjects with significant engraftment of SER-109 dose species. For each subject and antibiotic drug class, we calculated the change in abundance of AbRG between samples collected at baseline (after antibiotic therapy for an episode of C. difficile infection) and following treatment with SER-109 or placebo. We evaluated the effect of SER-109 engraftment on AbRG abundance, independent of dose. Results In subjects with significant high-confidence engraftment of SER-109 organisms (n = 30) we observed significantly greater reduction in AbRG relative to placebo at week 1 post treatment. These AbRG were associated with multiple classes of antibiotics including, but not limited to, cephalosporins (P = 0.035), and fluoroquinolones (P = 0.035) (Figure 1). Furthermore, the reduction of AbRG was correlated with the increased abundance of SER-109 dose species, and with a reduction in Proteobacteria (e.g., Enterobactericeae) (Figure 2). Conclusion Restoration of the gut microbiome with SER-109 in subjects with a history of rCDI is associated with a reduction in abundance of antibiotic resistance genes. These observations suggest that microbiome therapeutics could play a role in more rapidly decolonizing drug-resistant bacteria. Disclosures C. Ford, Seres Therapeutics, Inc: Employee and Shareholder, Salary. M. Henn, Seres Therapeutics, Inc: Employee and Shareholder, Salary. J. Bryant, Seres Therapeutics, Inc: Employee and Shareholder, Salary. L. Diao, Seres Therapeutics, Inc: Employee and Shareholder, Salary. J. Wortman, Seres Therapeutics, Inc: Employee and Shareholder, Salary. A. Tomlinson, Seres Therapeutics, Inc: Employee and Shareholder, Salary. K. Litcofsky, Seres Therapeutics, Inc: Employee and Shareholder, Salary. P. Bernardo, Seres Therapeutics, Inc: Employee and Shareholder, Salary. B. McGovern, Seres Therapeutics, Inc: Employee and Shareholder, Salary. J. G. Aunins, Seres Therapeutics, Inc: Employee and Shareholder, Salary. D. N. Cook, Seres Therapeutics, Inc: Employee and Shareholder, Salary. M. Trucksis, Seres Therapeutics, Inc: Employee and Shareholder, Salary.

scholarly journals Antibiotic resistance potential of the healthy preterm infant gut microbiome

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2928 ◽  
Author(s):  
Graham Rose ◽  
Alexander G. Shaw ◽  
Kathleen Sim ◽  
David J. Wooldridge ◽  
Ming-Shi Li ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Preterm Infant ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Taxonomic Diversity ◽  
Metagenomic Sequencing ◽  
Important Species ◽  
Antimicrobial Resistance Genes ◽  
Infant Gut Microbiome

Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities.

scholarly journals Withdraw of prophylactic antimicrobials does not change resistome in pigs

2019 ◽  
Author(s):  
Maria Fernanda Loayza Villa ◽  
Alejandro Torres ◽  
Lixin Zhang ◽  
Gabriel Trueba
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Resistant Bacteria ◽  
Productive Performance ◽  
Fitness Costs ◽  
Antibiotic Resistant ◽  
Human Microbiota ◽  
Antimicrobial Resistance Genes ◽  
The Impact

Abstract Background: The use of antimicrobials in the animal industry has increased the prevalence of antibiotic resistant bacteria and antimicrobial-resistance genes which can be transferred to human microbiota through the food chain or the environment. To reduce the influx of antibiotic-resistance to the human microbiota, restrictions on antimicrobials (in food animals) have been implemented in different countries. We investigated the impact of an antimicrobial restriction on the frequency of antimicrobial-resistant bacteria in pigs (PCI 1050) from an Ecuadorian farm. Results: No differences in antimicrobial resistant coliforms or antimicrobial resistance genes (richness and abundance) were found when we compared animals fed with or without antibiotics. Nevertheless, the absence of antimicrobials in pigs didn’t impact the productive performance of animals. Conclusion: Fitness costs of antimicrobial resistance in bacteria within intestinal microbiota of animals seems to be overestimated. Avoiding antimicrobials as prophylactics in pigs fed is not enough to control maintenance and spread of antimicrobial resistance.

scholarly journals Multidrug-resistant enterococci in the hospital environment: detection of novel vancomycin-resistant E. faecium clone ST910

2016 ◽  
Vol 10 (08) ◽  
pp. 799-806 ◽  
Author(s):  
Raoudha Dziri ◽  
Carmen Lozano ◽  
Leila Ben Said ◽  
Ridha Bellaaj ◽  
Abdellatif Boudabous ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Positive Sample ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Antimicrobial Resistance Genes ◽  
Vancomycin Resistant

Introduction: The role of the hospital environment as a reservoir of resistant bacteria in Tunisia has been poorly investigated; however, it could be responsible for the transmission of multidrug-resistant bacteria. The objective was to study the prevalence of Enterococcus in the environment of a Tunisian hospital and the antibiotic resistance phenotype/genotype in recovered isolates, with special reference to vancomycin resistance. Methodology: A total of 300 samples were taken (March–June, 2013) and inoculated in Slanetz-Bartley agar plates supplemented or not supplemented with 8 µg/mL of vancomycin. Antibiotic resistance genes were tested by polymerase chain reaction (PCR). The clonal relatedness of the vanA isolates was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence testing (MLST). Results: Enterococci were recovered in 33.3% of tested samples inoculated in SB medium. E faecium was the most prevalent species, followed by E. faecalis and E. casseliflavus. Antimicrobial resistance genes detected were as follows (number of isolates): erm(B) (71), tet(M) (18), aph(3’)-IIIa (27), ant(6)-Ia (15), cat(A) (4), and van(C2) (6). Vancomycin-resistant-enterococci (VRE) were recovered from 14 samples (4.7%), when tested in SB-VAN. The 14 VRE (one per positive sample) were identified as E. faecium and contained the van(A),erm(B), tet(M), ant(6)-Ia, and aph(3’)-IIIa genes. Thirteen of the VRE strains were ascribed by PFGE and MLST to a novel clone (new ST910), and only one VRE strain was typed as ST80 included in CC17. Conclusions: The emergence and spread of new clones of VRE, especially in the hospital environment in this country, could become particularly problematic.

scholarly journals Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Mohammad Aminul Islam ◽  
Moydul Islam ◽  
Rashedul Hasan ◽  
M. Iqbal Hossain ◽  
Ashikun Nabi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Tap Water ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

scholarly journals Prevalence And Characterization Of Plasmid-Mediated Quinolone Resistance In Various Aquatic Sources

2021 ◽  
Author(s):  
Farhan Yusuf ◽  
Kimberley Gilbride
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Quinolone Resistance ◽  
Resistant Bacteria ◽  
Rrna Gene ◽  
Environmental Isolates ◽  
Topoisomerase Iv ◽  
Phenotypic Resistance ◽  
Ciprofloxacin Resistance

Bacterial isolates found in aquatic ecosystems often carry antibiotic resistance genes (ARGs). These ARGs are often found on plasmids and transposons, which allows them to be proliferate throughout bacterial communities via horizontal gene transfer (HGT) causing dissemination of multidrug resistance. The increase in antibiotic resistance has raised concerns about the ability to continue to use these drugs to fight infectious diseases. Novel synthetic antibiotics like ciprofloxacin that are not naturally found in the environment were developed to prevent resistances. However, ciprofloxacin resistance has occurred through chromosomal gene mutations of type 2 topoisomerases or by the acquisition of plasmid-mediated quinolone resistances (PMQR). A particular PMQR, qnr genes, encoding for pentapeptide repeat proteins that confer low levels of quinolone resistance and protect DNA gyrase and topoisomerase IV from antibacterial activity. These qnr genes have been identified globally in both clinical and environmental isolates. The aim of this study was to determine the prevalence of ciprofloxacin-resistant bacteria in aquatic environments in the Greater Toronto Area and the potential dissemination of ciprofloxacin resistance. With the selective pressure of ciprofloxacin, we hypothesize that ciprofloxacin-resistant bacteria (CipR) in the environment may carry PMQR mechanisms while the sensitive population (CipS) would not carry PMQR genes. Isolates were tested for resistance to an additional 12 different antibiotics and identified using Sanger sequencing PCR products of the 16S rRNA gene. To determine which genes are responsible for ciprofloxacin resistance, multiplex PCR of associated qnr genes, qnrA, qnrB, and qnrS, was carried out on 202 environmental isolates. Our data demonstrate a similar prevalence of qnr genes was found in CipR (19%) and CipS (14%) populations suggesting that the presence of these genes was not necessarily correlated with the phenotypic resistance to the antibiotic. Furthermore, ciprofloxacinresistant bacteria were found in all locations at similar frequencies suggesting that resistance genes are widespread and could possibly arise through HGT events. Overall, determining the underlying cause and prevalence of ciprofloxacin resistance could help re-establish the effectiveness of these antimicrobial compounds.

scholarly journals Antibiotic resistance in lactococci and enterococci: phenotypic and molecular-genetic aspects

2017 ◽  
Vol 1 (1) ◽  
pp. 10-17
Author(s):  
Danuta Plotnikava ◽  
Anastasiya Sidarenka ◽  
Galina Novik
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Antibiotic Resistance Genes ◽  
Public Health Problem ◽  
Animal Husbandry ◽  
Resistant Bacteria ◽  
Monitoring And Control ◽  
Bacterial Drug Resistance

Abstract Extensive use of antibiotics in medicine, veterinary practice and animal husbandry has promoted the development and dissemination of bacterial drug resistance. The number of resistant pathogens causing common infectious diseases increases rapidly and creates worldwide public health problem. Commensal bacteria, including lactic acid bacteria of genera Enterococcus and Lactococcus colonizing gastrointestinal and urogenital tracts of humans and animals may act as vehicles of antibiotic resistance genes similar to those found in pathogens. Lactococci and enterococci are widely used in manufacturing of fermented products and as probiotics, therefore monitoring and control of transmissible antibiotic resistance determinants in industrial strains of these microorganisms is necessary to approve their Qualified Presumption of Safety status. Understanding the nature and molecular mechanisms of antibiotic resistance in enterococci and lactococci is essential, as intrinsic resistant bacteria pose no threat to environment and human health in contrast to bacteria with resistance acquired through horizontal transfer of resistance genes. The review summarizes current knowledge concerning intrinsic and acquired antibiotic resistance in Lactococcus and Enterococcus genera, and discusses role of enterococci and lactococci in distribution of this feature.

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