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    • br Funding Sources This work

    2018-10-25


    Funding Sources This work was supported by the National Institute of Allergy and Infectious Disease Grants: AI102435, AI120364, and AI122399. The funding sources had no role in the writing of this manuscript or the decision to submit it for publication.
    Conflict of Interest Statement
    Authors’ Contributions
    Acknowledgements
    Introduction The scale of clinical and public health problems due to multidrug-resistant bacterial infections has further escalated in recent years following the emergence of blaNDM, a plasmid-borne carbapenem resistance gene that has been widely disseminated among various species of bacterial pathogens worldwide (Kumarasamy et al., 2010; Nordmann et al., 2012). Descriptions such as “superbug”, “nightmare bacteria” and “post-antibiotic era” reflected the seriousness of the antimicrobial resistance issue. Among the major multidrug-resistant organisms that emerged within the past two decades, carbapenem-resistant Enterobacteriaceae (CRE), which commonly cause untreatable and hard-to-treat infections among hospitalized patients, is considered an urgent threat according to a report by the Center for Diseases Control and Prevention (CDC) in 2013 on Linsitinib threats in the United States. In the past two decades, utilization of carbapenems such as imipenem and meropenem in clinical treatments has become necessary due to proliferation of multidrug-resistant bacterial pathogens in clinical settings (Zilberberg and Shorr, 2013; Goel et al., 2011). Such increase in carbapenem consumption has been accompanied by the emergence of carbapenem-resistant Gram-negative pathogens (Karaiskos and Giamarellou, 2014; Livermore, 2004, 2009). According to the CDC report of 2013, >9000 healthcare-associated infections are caused by CRE each year and almost half of the hospital patients who suffer from CRE-mediated bloodstream infections died subsequently (CDC, 2013). Each year, approximately 600 deaths result from infections caused by the two most common types of CRE, namely carbapenem-resistant Klebsiella spp. and E. coli (Yong et al., 2009). In China, the first clinical report of blaNDM involved carbapenem-resistant Acinetobacter baumannii strains detectable in four patients who resided in different provinces, in 2011 (Chen et al., 2011). Since then it has been recoverable in most species of Enterobacteriaceae, including K. pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes and Citrobacter freundii, in various cities or regions in China, such as Beijing, Changsha, Chongqing, Fuzhou, Guangzhou, Hangzhou, Hebei, Hong Kong and Zhengzhou (Berrazeg et al., 2014; Qin et al., 2014). The first KPC producing CRE strain in China was reported in 2007, and the blaKPC-2 gene has since become the most widely spread carbapenemase gene in China as well as various parts of the world. In this study, we conducted a nationwide surveillance of the prevalence of CRE in China and investigated the molecular epidemiological features of these strains, and hoped to identify the key strains and mobile resistance elements responsible for causing an increase in prevalence of CRE-mediated infections in China. Findings of this work shall provide essential insight into development of effective strategies for worldwide control of CRE and reducing the rate of untreatable infections in clinical settings.
    Materials and Methods
    Results
    Discussion Findings of this work confirmed that production of carbapenemases is the major mechanism of carbapenem resistance in CRE in China, among which NDM and KPC-2 were the major carbapenemases concerned. These data provide important insight into the development anti-CRE therapy in China, and demonstrated that the types of resistance genes harbored by CRE strains differed significantly from one region to another. In particular, our data contradicted those of a recent meta surveillance conducted in European countries, which showed that only 71% of CRE were carbapenemase-producing, among which a wide variety of carbapenemases were detected (Grundmann et al., 2016).