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      High burden of infections caused by ESBL-producing MDR Escherichia coli in paediatric patients, Yangon, Myanmar

      brief-report
      , , ,
      Jac-Antimicrobial Resistance
      Oxford University Press

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          Abstract

          Background

          There is mounting evidence of a high burden of antimicrobial-resistant infections in children in low- and middle-income countries (LMICs).

          Objectives

          To detect the frequency of ESBL-producing Escherichia coli in clinical specimens from paediatric patients attending Yangon Children’s Hospital in Myanmar.

          Methods

          All children attending Yangon Children’s Hospital who had clinical specimens submitted to the hospital diagnostic microbiology laboratory from June 2019 to December 2019 were included in the study. Specimens were processed routinely using standard methods with BD Phoenix used for pathogen identification and susceptibility testing. Presence of ESBLs was determined using the cephalosporin/clavulanate combination disc method with confirmation by PCR.

          Results

          From 3462 specimens submitted to the Microbiology Laboratory, a total of 123 E. coli were isolated. Among them, 100 isolates were phenotypically ESBL producers, 94 (76.4%) of which were confirmed by PCR [82/94 (87%) CTX-M, 72/94 (77%) TEM, 1/94 (1%) SHV]. Most of the ESBL-producing E. coli were isolated from urine samples (52.1%, 49/94) and the majority were from the surgical unit (61.7%, 58/94). Only 34/94 (36%) isolates were susceptible to meropenem.

          Conclusions

          This study confirms a high proportion of infections caused by ESBL-producing and MDR E. coli in children hospitalized in Yangon, where access to effective second-line antimicrobials is limited.

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          Most cited references14

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          Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern.

          The medical community relies on clinical expertise and published guidelines to assist physicians with choices in empirical therapy for system-based infectious syndromes, such as community-acquired pneumonia and urinary-tract infections (UTIs). From the late 1990s, multidrug-resistant Enterobacteriaceae (mostly Escherichia coli) that produce extended-spectrum beta lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of UTIs. Recent reports have also described ESBL-producing E coli as a cause of bloodstream infections associated with these community-onset UTIs. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Thus, more rapid diagnostic testing of ESBL-producing bacteria and the possible modification of guidelines for community-onset bacteraemia associated with UTIs are required.
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            Global epidemiology of CTX-M β-lactamases: temporal and geographical shifts in genotype.

            Globally, rates of ESBL-producing Enterobacteriaceae are rising. We undertook a literature review, and present the temporal trends in blaCTX-M epidemiology, showing that blaCTX-M-15 and blaCTX-M-14 have displaced other genotypes in many parts of the world. Explanations for these changes can be attributed to: (i) horizontal gene transfer (HGT) of plasmids; (ii) successful Escherichia coli clones; (iii) ESBLs in food animals; (iv) the natural environment; and (v) human migration and access to basic sanitation. We also provide explanations for the changing epidemiology of blaCTX-M-2 and blaCTX-M-27. Modifiable anthropogenic factors, such as poor access to basic sanitary facilities, encourage the spread of blaCTX-M and other antimicrobial resistance (AMR) genes, such as blaNDM, blaKPC and mcr-1. We provide further justification for novel preventative and interventional strategies to reduce transmission of these AMR genes.
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              The CTX-M beta-lactamase pandemic.

              In the past decade CTX-M enzymes have become the most prevalent extended-spectrum beta-lactamases, both in nosocomial and in community settings. The insertion sequences (ISs) ISEcp1 and ISCR1 (formerly common region 1 [CR1] or orf513) appear to enable the mobilization of chromosomal beta-lactamase Kluyvera species genes, which display high homology with blaCTX-Ms. These ISs are preferentially linked to specific genes: ISEcp1 to most blaCTX-Ms, and ISCR1 to blaCTX-M-2 or blaCTX-M-9. The blaCTX-M genes embedded in class 1 integrons bearing ISCR1 are associated with different Tn402-derivatives, and often with mercury Tn21-like transposons. The blaCTX-M genes linked to ISEcp1 are often located in multidrug resistance regions containing different transposons and ISs. These structures have been located in narrow and broad host-range plasmids belonging to the same incompatibility groups as those of early antibiotic resistance plasmids. These plasmids frequently carry aminoglycoside, tetracycline, sulfonamide or fluoroquinolone resistance genes [qnr and/or aac(6')-Ib-cr], which would have facilitated the dissemination of blaCTX-M genes because of co-selection processes. In Escherichia coli, they are frequently carried in well-adapted phylogenetic groups with particular virulence-factor genotypes. Also, dissemination has been associated with different clones (CTX-M-9 or CTX-M-14 producers) or epidemic clones associated with specific enzymes such as CTX-M-15. All these events might have contributed to the current pandemic CTX-M beta-lactamase scenario.
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                Author and article information

                Contributors
                Journal
                JAC Antimicrob Resist
                JAC Antimicrob Resist
                jacamr
                Jac-Antimicrobial Resistance
                Oxford University Press
                2632-1823
                March 2021
                14 February 2021
                14 February 2021
                : 3
                : 1
                : dlab011
                Affiliations
                [1 ] Yangon Children’s Hospital , Yangon, Myanmar
                [2 ] Myanmar Oxford Clinical Research Unit , Yangon, Myanmar
                [3 ] Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit , Vientiane, Lao People's Democratic Republic
                [4 ] Centre for Tropical Medicine and Global Health, University of Oxford , Oxford, UK
                [5 ] University of Medicine 2 , Yangon, Myanmar
                Author notes
                Corresponding author. E-mail: drthidarsan@ 123456gmail.com
                Author information
                http://orcid.org/0000-0001-9804-2927
                http://orcid.org/0000-0002-7620-4822
                Article
                dlab011
                10.1093/jacamr/dlab011
                7882151
                33615221
                4c045c3e-09fc-4036-a3fa-543ba1728ecc
                © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 November 2020
                : 19 January 2021
                Page count
                Pages: 4
                Funding
                Funded by: Department of Medical Research in Myanmar;
                Award ID: 9/2019
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: 220211
                Categories
                Brief Report

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