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      Emergence of Almost Identical F36:A-:B32 Plasmids Carrying  bla NDM-5 and  qepA in  Escherichia coli from Both Pakistan and Canada

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          Abstract

          The New Delhi Metallo-β-lactamase (NDM) producing Enterobacteriaceae is spreading worldwide. Although the bla NDM gene has been identified in animal associated Enterobacteriaceae isolates in many countries, little is known about its occurrence in animal products in Pakistan. In this study, 13 Escherichia coli isolates were collected from chicken meat samples in Pakistan. Two isolates, 15978 and C4109, exhibited reduced susceptibility (MIC ≥1 μg/mL) to imipenem, and carried bla NDM-5 and bla NDM-7 gene, respectively. Whole-genome sequencing and Oxford Nanopore MinION sequencing revealed that 15978 and C4109 belonged to ST156 and ST167, respectively. bla NDM-7 was carried by an IncX3 plasmid that has disseminated worldwide, whereas bla NDM-5 was located on an F36: A-: B32 plasmid, which shared high identity with two plasmids carried by E. coli isolates from other countries (one from a patient in Canada). To the best of our knowledge, this is the first report characterizing bla NDM-carrying plasmids from chicken meat samples in Pakistan. The dissemination of almost identical bla NDM-5-bearing F36:A-:B32 and bla NDM-7-bearing IncX3 plasmids in different countries highlights the importance of international trade and travel in the spread of antimicrobial resistance strains and plasmids worldwide.

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          Most cited references16

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          Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

          Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam–β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing Enterobacteriaceae (CPE), only some “second-line” drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.
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            NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

            SUMMARY New Delhi metallo-β-lactamase (NDM) is a metallo-β-lactamase able to hydrolyze almost all β-lactams. Twenty-four NDM variants have been identified in >60 species of 11 bacterial families, and several variants have enhanced carbapenemase activity. Klebsiella pneumoniae and Escherichia coli are the predominant carriers of bla NDM , with certain sequence types (STs) (for K. pneumoniae , ST11, ST14, ST15, or ST147; for E. coli , ST167, ST410, or ST617) being the most prevalent. NDM-positive strains have been identified worldwide, with the highest prevalence in the Indian subcontinent, the Middle East, and the Balkans. Most bla NDM -carrying plasmids belong to limited replicon types (IncX3, IncFII, or IncC). Commonly used phenotypic tests cannot specifically identify NDM. Lateral flow immunoassays specifically detect NDM, and molecular approaches remain the reference methods for detecting bla NDM . Polymyxins combined with other agents remain the mainstream options of antimicrobial treatment. Compounds able to inhibit NDM have been found, but none have been approved for clinical use. Outbreaks caused by NDM-positive strains have been reported worldwide, attributable to sources such as contaminated devices. Evidence-based guidelines on prevention and control of carbapenem-resistant Gram-negative bacteria are available, although none are specific for NDM-positive strains. NDM will remain a severe challenge in health care settings, and more studies on appropriate countermeasures are required.
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              Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production

              By 2030, the global population will be 8.5 billion, placing pressure on international poultry production, of which China is a key producer1. From April 2017, China will implement the withdrawal of colistin as a growth promoter, removing over 8,000 tonnes per year from the Chinese farming sector2. To understand the impact of banning colistin and the epidemiology of multi-drug-resistant (MDR) Escherichia coli (using blaNDM and mcr-1 as marker genes), we sampled poultry, dogs, sewage, wild birds and flies. Here, we show that mcr-1, but not blaNDM, is prevalent in hatcheries, but blaNDM quickly contaminates flocks through dogs, flies and wild birds. We also screened samples directly for resistance genes to understand the true breadth and depth of the environmental and animal resistome. Direct sample testing for blaNDM and mcr-1 in hatcheries, commercial farms, a slaughterhouse and supermarkets revealed considerably higher levels of positive samples than the blaNDM- and mcr-1-positive E. coli, indicating a substantial segment of unseen resistome-a phenomenon we have termed the 'phantom resistome'. Whole-genome sequencing identified common blaNDM-positive E. coli shared among farms, flies, dogs and farmers, providing direct evidence of carbapenem-resistant E. coli transmission and environmental contamination.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                IDR
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                30 December 2019
                2019
                : 12
                : 3981-3985
                Affiliations
                [1 ]College of Veterinary Medicine, South China Agricultural University , Guangzhou 510642, People’s Republic of China
                [2 ]Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University , Guangzhou, People’s Republic of China
                [3 ]Government College University , Faisalabad 54000, Pakistan
                Author notes
                Correspondence: Jian-Hua Liu College of Veterinary Medicine, South China Agricultural University , Guangzhou, Guangdong, People’s Republic of China Email jhliu@scau.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-7873-1343
                Article
                236766
                10.2147/IDR.S236766
                6941701
                31920350
                7f53be85-4175-4ac6-93bd-58e37f7acaa6
                © 2019 Baloch 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
                : 31 October 2019
                : 10 December 2019
                Page count
                Figures: 1, Tables: 1, References: 27, Pages: 5
                Categories
                Short Report

                Infectious disease & Microbiology
                plasmid,animal food,carbapenemase,blandm
                Infectious disease & Microbiology
                plasmid, animal food, carbapenemase, blandm

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