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      Genomic surveillance of Escherichia coli in municipal wastewater treatment plants as an indicator of clinically relevant pathogens and their resistance genes

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          Abstract

          We examined whether genomic surveillance of Escherichia coli in wastewater could capture the dominant E. coli lineages associated with bloodstream infection and livestock in the East of England, together with the antibiotic-resistance genes circulating in the wider E. coli population. Treated and untreated wastewater was taken from 20 municipal treatment plants in the East of England, half in direct receipt of acute hospital waste. All samples were culture positive for E. coli , and all but one were positive for extended-spectrum β-lactamase (ESBL)-producing E. coli . The most stringent wastewater treatment (tertiary including UV light) did not eradicate ESBL- E. coli in 2/3 cases. We sequenced 388 E. coli (192 ESBL, 196 non-ESBL). Multilocus sequence type (ST) diversity was similar between plants in direct receipt of hospital waste versus the remainder (93 vs 95 STs, respectively). We compared the genomes of wastewater E. coli with isolates from bloodstream infection ( n=437), and livestock farms and retail meat ( n=431) in the East of England. A total of 19/20 wastewater plants contained one or more of the three most common STs associated with bloodstream infection (ST131, ST73, ST95), and 14/20 contained the most common livestock ST (ST10). In an analysis of 1254 genomes (2 cryptic E. coli were excluded), wastewater isolates were distributed across the phylogeny and intermixed with isolates from humans and livestock. Ten bla CTX-M elements were identified in E. coli isolated from wastewater, together with a further 47 genes encoding resistance to the major antibiotic drug groups. Genes encoding resistance to colistin and the carbapenems were not detected. Genomic surveillance of E. coli in wastewater could be used to monitor new and circulating lineages and resistance determinants of public-health importance.

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          Most cited references25

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          SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments

          Rapidly decreasing genome sequencing costs have led to a proportionate increase in the number of samples used in prokaryotic population studies. Extracting single nucleotide polymorphisms (SNPs) from a large whole genome alignment is now a routine task, but existing tools have failed to scale efficiently with the increased size of studies. These tools are slow, memory inefficient and are installed through non-standard procedures. We present SNP-sites which can rapidly extract SNPs from a multi-FASTA alignment using modest resources and can output results in multiple formats for downstream analysis. SNPs can be extracted from a 8.3 GB alignment file (1842 taxa, 22 618 sites) in 267 seconds using 59 MB of RAM and 1 CPU core, making it feasible to run on modest computers. It is easy to install through the Debian and Homebrew package managers, and has been successfully tested on more than 20 operating systems. SNP-sites is implemented in C and is available under the open source license GNU GPL version 3.
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            Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.

            Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
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              Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis.

              We performed a systematic review and meta-analysis to examine the impact of extended-spectrum beta-lactamase (ESBL) production on mortality and delay in effective therapy in Enterobacteriaceae bacteraemia. We searched the PubMed database using the terms 'bacteremia or bloodstream' and 'ESBL or extended-spectrum beta-lactamase'. Included studies contained numbers of and mortality figures for patients with bacteraemia caused by ESBL producers and non-producers. Data extracted included crude relative risk (RR), adjusted odds ratio and 95% confidence intervals (CIs) for mortality and delayed effective therapy. Results were pooled using a random effects model. Sixteen studies met inclusion criteria. Meta-analysis of crude RRs demonstrated significantly increased mortality in ESBL-associated bacteraemia (pooled RR 1.85, 95% CI 1.39-2.47, P < 0.001). However, only one study reported RR controlled for confounding. Ten studies reported comparative data on delay in effective therapy. Meta-analysis of crude RRs demonstrated significantly increased incidence of delay in effective therapy in ESBL-associated bacteraemia (pooled RR 5.56, 95% CI 2.94-10.51, P < 0.001). In Enterobacteriaceae bacteraemia, ESBL production is associated with increased mortality and delay in effective therapy. However, lack of controlled studies limits interpretation regarding causality, and further controlled studies are required.
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                Author and article information

                Journal
                Microb Genom
                Microb Genom
                mgen
                mgen
                Microbial Genomics
                Microbiology Society
                2057-5858
                May 2019
                20 May 2019
                20 May 2019
                : 5
                : 5
                : e000267
                Affiliations
                [1 ]departmentDepartment of Medicine , University of Cambridge , Box 157 Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0QQ, UK
                [2 ]London School of Hygiene and Tropical Medicine , Keppel Street, London WC1E 7HT, UK
                [3 ]Clinical Microbiology and Public Health Laboratory, Public Health England , Cambridge CB2 0QQ, UK
                [4 ]Wellcome Sanger Institute, Wellcome Trust Genome Campus , Hinxton, Cambridge CB10 1SA, UK
                Author notes
                *Correspondence: Kathy E. Raven, ker37@ 123456medschl.cam.ac.uk
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-7069-5958
                https://orcid.org/0000-0002-1718-2782
                Article
                000267
                10.1099/mgen.0.000267
                6562247
                31107200
                dde63ad5-49d5-4299-9f41-c2caf711fdab
                © 2019 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 January 2019
                : 24 March 2019
                Categories
                Research Article
                Microbial evolution and epidemiology: Population Genomics
                Custom metadata
                0

                escherichia coli,genomic surveillance,resistance,wastewater

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