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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

Microbial Genomics

Microbiology Society

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### Abstract

We examined whether genomic surveillance of in wastewater could capture the dominant lineages associated with bloodstream infection and livestock in the East of England, together with the antibiotic-resistance genes circulating in the wider 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 , and all but one were positive for extended-spectrum β-lactamase (ESBL)-producing . The most stringent wastewater treatment (tertiary including UV light) did not eradicate ESBL- in 2/3 cases. We sequenced 388 (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 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 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 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 in wastewater could be used to monitor new and circulating lineages and resistance determinants of public-health importance.

### Most cited references24

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### Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.

(2009)
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.

(2007)
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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### Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131

ABSTRACT Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131.
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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
###### 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.

###### Article
000267
10.1099/mgen.0.000267
6562247
31107200