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      Distribution of ß-Lactamase Genes Among Multidrug-Resistant and Extended-Spectrum ß-Lactamase-Producing Diarrheagenic Escherichia coli from Under-Five Children in Ethiopia

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          Abstract

          Purpose

          Escherichia coli strains that produce extended-spectrum ß-lactamase (ESBL) and carbapenemase are among the major threats to global health. The objective of the present study was to determine the distribution of ß-lactamase genes among multidrug-resistant (MDR) and ESBL-producing Diarrheagenic E. coli (DEC) pathotypes isolated from under-five children in Ethiopia.

          Patients and Methods

          A cross-sectional study was conducted in Addis Ababa and Debre Berhan, Ethiopia. It was a health-facility-based study and conducted between December 2020 and August 2021. A total of 476 under-five children participated in the study. DEC pathotypes were detected by conventional Polymerase Chain Reaction (PCR) assay. After evaluating the antimicrobial susceptibility profile of the DEC strains by disk diffusion method, confirmation test was done for ESBL and carbapenemase production. ß-lactamase encoding genes were identified from phenotypically ESBLs and carbapenemase positive DEC strains using PCR assay.

          Results

          In total, 183 DEC pathotypes were isolated from the 476 under-five children. Seventy-nine (43%, 79/183) MDR-DEC pathotypes were identified. MDR was common among enteroaggregative E. coli (EAEC) (58%, 44/76), followed by enterotoxigenic E. coli (ETEC) (44%, 17/39)) and enteroinvasive E. coli (EIEC) (30%, 7/23). Phenotypically, a total of 30 MDR-DEC pathotypes (16.4%, 30/183) were tested positive for ESBLs. Few ETEC (5.1%, 2/39) and EAEC (2.6%, 2/76) were carbapenemase producers. The predominant β-lactamase genes identified was bla TEM (80%, 24/30) followed by bla CTX -M (73%, 22/30), bla SHV (60%, 18/30), bla NDM (13%, 4/30), and bla OXA -48 (13%, 4/30). Majority of the ß-lactamase encoding genes were detected in EAEC (50%) and ETEC (20%). Co-existence of different β-lactamase genes was found in the present study.

          Conclusion

          The bla TEM, bla CTX-M, bla SHV, bla NDM , and bla OXA-48 , that are associated with serious and urgent threats globally, were detected in diarrheagenic E. coli isolates from under-five children in Ethiopia. This study also revealed the coexistence of the β-lactamase genes.

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          Most cited references71

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          Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided. © 2011 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.
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            Carbapenemases: the versatile beta-lactamases.

            Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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              Antimicrobial resistance: a global multifaceted phenomenon.

              Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern - Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis - for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                06 November 2023
                2023
                : 16
                : 7041-7054
                Affiliations
                [1 ]Department of Microbiology, Immunology and Parasitology, Addis Ababa University , Addis Ababa, Ethiopia
                [2 ]Department of Medical Laboratory Science, Debre Berhan University , Debre Berhan, Ethiopia
                [3 ]Aklilu Lemma Institute of Pathobiology, Addis Ababa University , Addis Ababa, Ethiopia
                [4 ]Ohio State University, Global One Health LLC , Addis Ababa, Ethiopia
                [5 ]Department of Medical Laboratory, Tikur Anbessa Specialized Hospital, Addis Ababa University , Addis Ababa, Ethiopia
                [6 ]Bacterial and Viral Disease Research Directorate, Armauer Hansen Research Institute (AHRI) , Addis Ababa, Ethiopia
                Author notes
                Correspondence: Tizazu Zenebe, Department of Medical Laboratory Science, Debre Berhan University , P.O.Box 445, Debre Berhan, Ethiopia, Tel +251912372837, Email tizazuzenebe@yahoo.com
                Author information
                http://orcid.org/0000-0003-4607-944X
                http://orcid.org/0000-0002-6686-2370
                http://orcid.org/0000-0003-1510-8711
                http://orcid.org/0000-0002-6100-9303
                Article
                432743
                10.2147/IDR.S432743
                10637226
                735fa8fe-d924-4111-ac54-108faf73dc12
                © 2023 Zenebe et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 28 August 2023
                : 26 October 2023
                Page count
                Figures: 3, Tables: 5, References: 74, Pages: 14
                Funding
                Funded by: Addis Ababa University, open-funder-registry 10.13039/501100007941;
                This work was funded by Addis Ababa University with grant number VPRTTPY-0402018.
                Categories
                Original Research

                Infectious disease & Microbiology
                diarrheagenic e. coil,under-five children,ß-lactamase,carbapenemase,esbl,multidrug resistance,ethiopia

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