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      Carriage of carbapenemase‐ and extended‐spectrum cephalosporinase‐producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia; gender and age differences and detection of bla OXA‐48 in humans

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          Abstract

          Objectives

          This study investigates the frequency and characteristics of carbapenemase‐producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended‐spectrum cephalosporinase‐producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.

          Methods

          Faecal samples were obtained from 307 humans and 285 livestock including large ruminants, pigs and poultry living in 100 households in rural Cambodia in 2011. Each household was interviewed, and multilevel logistic model determined associations between household practices/meat consumption and faecal carriage of ESCE/K. CPE and ESCE/K were detected and further screened for colistin resistance genes.

          Results

          CPE/K isolates harbouring bla OXA‐48 were identified in two humans. The community carriage of ESCE/K was 20% in humans and 23% in livestock. The same ESBL genes: bla CTX‐M‐15, bla CTX‐M‐14, bla CTX‐M‐27, bla CTX‐M‐55, bla SHV‐2, bla SHV‐12, bla SHV‐28; AmpC genes: bla CMY‐2, bla CMY‐42, bla DHA‐1; and colistin resistance genes: mcr‐1‐like and mcr‐3‐like were detected in humans and livestock. ESCE/K was frequently detected in women, young children, pigs and poultry, which are groups in close contact. The practice of burning or burying meat waste and not collecting animal manure indoors and outdoors daily were identified as risk factors for faecal carriage of ESCE/K.

          Conclusions

          Faecal carriage of E. coli and K. pneumoniae harbouring extended‐spectrum cephalosporinase genes are common in the Cambodian community, especially in women and young children. Exposure to animal manure and slaughter products are risk factors for intestinal colonization of ESCE/K in humans.

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          Most cited references55

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          Carbapenems: past, present, and future.

          In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as "slow substrates" or inhibitors of β-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
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            Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes

            Background and aim Plasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between amplicons. The primer pairs and amplification conditions allow for single or multiple detection of all currently described mcr genes and their variants present in Enterobacteriaceae. The protocol was validated testing 49 European Escherichia coli and Salmonella isolates of animal origin. Results: Multiplex PCR results in bovine and porcine isolates from Spain, Germany, France and Italy showed full concordance with whole genome sequence data. The method was able to detect mcr-1, mcr-3 and mcr-4 as singletons or in different combinations as they were present in the test isolates. One new mcr-4 variant, mcr-4.3, was also identified. Conclusions: This method allows rapid identification of mcr-positive bacteria and overcomes the challenges of phenotypic detection of colistin resistance. The multiplex PCR should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing.
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              Fecal Colonization With Extended-spectrum Beta-lactamase-Producing Enterobacteriaceae and Risk Factors Among Healthy Individuals: A Systematic Review and Metaanalysis.

              Gut colonization is a risk factor for infections with extended-spectrum beta-lactamase (ESBL)-producing organisms. We aimed to determine the ESBL class A reservoir among healthy individuals.
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                Author and article information

                Contributors
                clara.atterby@medsci.uu.se
                Journal
                Zoonoses Public Health
                Zoonoses Public Health
                10.1111/(ISSN)1863-2378
                ZPH
                Zoonoses and Public Health
                John Wiley and Sons Inc. (Hoboken )
                1863-1959
                1863-2378
                02 July 2019
                September 2019
                : 66
                : 6 ( doiID: 10.1111/zph.v66.6 )
                : 603-617
                Affiliations
                [ 1 ] Zoonosis Science Center, Department of Medical Sciences Uppsala University Uppsala Sweden
                [ 2 ] Division of Reproduction, Department of Clinical Sciences Swedish University of Agricultural Sciences (SLU) Uppsala Sweden
                [ 3 ] Food and Agriculture Organization of the United Nations Phnom Penh Cambodia
                [ 4 ] Institute of Environmental Engineering ETH Zürich Switzerland
                [ 5 ] Center for Ecology and Evolution in Microbial Model Systems Linnaeus University Kalmar Sweden
                [ 6 ] Department of Infectious Diseases, Kalmar County Council, Department of Clinical and Experimental Medicine Linköping University Linköping Sweden
                [ 7 ] Diagnostic Centrum, Clinic Microbiologic Laboratory Kalmar County Hospital Kalmar Sweden
                [ 8 ] General Directorate of Animal Health and Production Ministry of Agriculture, Forestry and Fisheries Phnom Penh Cambodia
                [ 9 ] Department of Animal Health and Antimicrobial strategies National Veterinary Institute (SVA) Uppsala Sweden
                [ 10 ] Department of Clinical and Experimental Medicine Linköping University Sweden
                Author notes
                [*] [* ] Correspondence

                Clara Atterby, Zoonosis Science Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

                Email: clara.atterby@ 123456medsci.uu.se

                Author information
                https://orcid.org/0000-0001-7360-5383
                Article
                ZPH12612
                10.1111/zph.12612
                6852310
                31264805
                fb403c15-c8f6-45bf-8465-ea79cfa15829
                © 2019 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 November 2018
                : 20 May 2019
                : 21 May 2019
                Page count
                Figures: 5, Tables: 1, Pages: 15, Words: 10587
                Funding
                Funded by: Swedish Civil Contingencies Agency , open-funder-registry 10.13039/501100007294;
                Funded by: Swedish International Development Cooperation Agency , open-funder-registry 10.13039/100004441;
                Award ID: 2010-7876
                Funded by: Swedish Research Council VR , open-funder-registry 10.13039/501100004359;
                Award ID: 2016-02606
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                September 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:13.11.2019

                ampc,cambodia,carbapenemase,colistin,esbl,risk factors,rural population,zoonoses

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