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      Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China

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          ABSTRACT

          The global spread of carbapenem-resistant Enterobacteriaceae (CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance gene mcr-1 among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249 Enterobacteriaceae isolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Escherichia coli were the two most common CRE species, with Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% ( n = 589) of the K. pneumoniae isolates from the intensive care unit were carbapenem resistant. Furthermore, bla NDM-5 and mcr-1 were found to coexist in one E. coli isolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused by K. pneumoniae in the studied hospital.

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          Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study

          Karthikeyan K Kumarasamy, Mark Toleman, Timothy R. Walsh … (2010)
          Summary Background Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK. Methods Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK's national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene bla NDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan. Findings We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries. Interpretation The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Funding European Union, Wellcome Trust, and Wyeth.
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            Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1 -positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study

            Yang Wang, Guo-Bao Tian, Rong Zhang … (2017)
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              Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum β-lactamases: a systematic review and meta-analysis.

              Matthew E. Falagas, Giannoula Tansarli, Petros Rafailidis … (2012)
              To study the comparative mortality associated with carbapenems and alternative antibiotics for the treatment of patients with extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae bacteraemia. We searched systematically PubMed and Scopus databases for studies providing data for mortality among patients treated with carbapenems, β-lactam/β-lactamase inhibitor combinations (BL/BLIs) or non-BL/BLIs (mainly cephalosporins and fluoroquinolones), preferably as monotherapy. Studies focusing on patients of all ages with community- and healthcare-associated bacteraemia were eligible. Data were pooled using the technique of meta-analysis. Twenty-one articles, studying 1584 patients, were included. Escherichia coli and Klebsiella pneumoniae were the most commonly studied bacteria. Delay in appropriate treatment up to 6 days was reported. Carbapenems were used mainly as definitive therapy. Carbapenems were associated with lower mortality than non- BL/BLIs for definitive [risk ratio (RR) 0.65, 95% CI 0.47-0.91] and empirical (RR 0.50, 95% CI 0.33-0.77) treatment. No statistically significant differences in mortality were found between carbapenems and BL/BLIs administered as definitive (RR 0.52, 95% 0.23-1.13) or empirical (RR 0.91, 95% CI 0.66-1.25) treatment. BL/BLIs were not associated with lower mortality than non-BL/BLIs administered either definitively (RR 1.59, 95% 0.83-3.06) or empirically (RR 0.82, 95% 0.48-1.41). Data regarding subgroups according to the setting, comorbidity and bacterial species could not be extracted. Based on data from non-randomized studies, carbapenems may be considered the treatment of choice for empirical treatment of patients with ESBL-producing Enterobacteriaceae bacteraemia. The role of BL/BLIs should be further evaluated for definitive treatment. Further research should focus on faster identification of ESBL-positive pathogens and potential differences in the treatment of each bacterial species.
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                Author and article information

                Contributors
                Andrew B. Onderdonk: Role: Editor
                Journal
                Journal ID (nlm-ta): J Clin Microbiol
                Journal ID (iso-abbrev): J. Clin. Microbiol
                Journal ID (hwp): jcm
                Journal ID (pmc): jcm
                Journal ID (publisher-id): JCM
                Title: Journal of Clinical Microbiology
                Publisher: American Society for Microbiology (1752 N St., N.W., Washington, DC )
                ISSN (Print): 0095-1137
                ISSN (Electronic): 1098-660X
                Publication date (Electronic preprint): 31 January 2018
                Publication date (Electronic): 26 March 2018
                Publication date Collection: April 2018
                Volume: 56
                Issue: 4
                Electronic Location Identifier: e01932-17
                Affiliations
                [a ]Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou, China
                [b ]Department of Clinical Laboratory, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China
                [c ]Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China
                [d ]Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety and Beijing Laboratory for Food Quality and Safety, Beijing, China
                [e ]Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
                [f ]Department of Clinical Laboratory, Children's Hospital of Zhengzhou, Zhengzhou, China
                Brigham and Women's Hospital
                Author notes
                Address correspondence to Zhangqi Shen, szq@ 123456cau.edu.cn .

                Citation Li Y, Sun Q, Shen Y, Zhang Y, Yang J, Shu L, Zhou H, Wang Y, Wang B, Zhang R, Wang S, Shen Z. 2018. Rapid increase in prevalence of carbapenem-resistant Enterobacteriaceae (CRE) and emergence of colistin resistance gene mcr-1 in CRE in a hospital in Henan, China. J Clin Microbiol 56:e01932-17. https://doi.org/10.1128/JCM.01932-17.

                Author information
                https://orcid.org/0000-0003-0866-4584
                Article
                Accession ID: PMC5869811 Pmcid ID: PMC5869811 Pmc-uid ID: 5869811 Publisher ID: 01932-17
                DOI: 10.1128/JCM.01932-17
                PMC ID: 5869811
                PubMed ID: 29386265
                SO-VID: 65e5e0ec-ac06-4a53-8e31-3b24748e4b87
                Copyright © Copyright © 2018 American Society for Microbiology.
                License:

                All Rights Reserved.

                History
                Date received : 12 December 2017
                Date revision requested : 27 December 2017
                Date accepted : 24 January 2018
                Page count
                supplementary-material: 1, Figures: 1, Tables: 3, Equations: 0, References: 23, Pages: 7, Words: 4159
                Funding
                Funded by: National Natural Science Foundation of China (NSFC), https://doi.org/10.13039/501100001809;
                Award ID: 31672604
                Award ID: 81661138002
                Award Recipient :
                Categories
                Subject: Epidemiology
                Custom metadata
                cover-date April 2018

                Keywords: Klebsiella pneumoniae ,carbapenem resistance, Enterobacteriaceae , Escherichia coli
                Data availability:
                Keywords: Klebsiella pneumoniae , carbapenem resistance, Enterobacteriaceae , Escherichia coli

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