Although there is no evidence to suggest that CRE

Although there is no evidence to suggest that CRE originated from China, dissemination of such strains in China was found to be extremely rapid, eventually facilitating transmission to other parts of the world through traffic and trade. This study represents the first comprehensive nationwide surveillance of CRE in China to provide an overview of the genetic and phenotypic features of this category of multidrug resistant organisms in the country. The data is highly representative as the surveillance covers almost every province or municipal city. Key findings of this study are summarized as follows. First, blaKPC-2 and blaNDM were found to be the key carbapenemase genes responsible for mediating development of the carbapenem resistance phenotypes in CREs in China, with blaKPC-2 being the most common carbapenemase gene harbored by K. pneumoniae; however, blaNDM was found to be the predominant resistance gene in E. coli. Other carbapenemase genes such as blaIMP-4 were much less frequently detected; other elements such as blaVIM and blaOXA-48 were not detectable in a single clinical CRE strain tested in this work. Second, 21 out of 1105 CRE strains tested were found to carry multiple carbapenemase genes, in particular the blaNDM and blaKPC-2 combination, with K. pneumoniae being the most common species in this category. These observations urged the development of novel therapies to combat CRE in China. Current new Linsitinib cost such as ceftazidime-avibactam may not be suitable to treat CRE in China since a large proportion of CRE produce NDM carbapenemase, to which ceftazidime-avibactam is not active. Development of inhibitors targeting NDM and KPC-2 should be a feasible strategy to develop novel anti-CRE therapies. Although CRE exhibiting a range of strain types were detected in China, several unique strain types are clearly responsible for the increased rate of CRE infections in China. ST11 of K. pneumoniae, but not ST258, a common strain type reported worldwide, is the major strain type, which exhibited signs of multi-clonal dissemination. Other strain types were relatively rare and more sporadic, with ST23 (4%) and ST17 (2.6%) being the 2nd and 3rd most common strain types. Except for some regions, ST11 is the major CRKP in China. Genetic analysis showed that ST258 is not simply a distinct clone of ST11. These two types of CRKP shared about 3/4 of the common genome, while 1/4 of the ST258 genome is derived from other types of K. pneumonia (Liang Chen et al., 2014). The genetic basis of predominant prevalence of ST11 in China and ST258 in other part of the world is not well understood. Unlike ST11, which was strictly associated with KPC-2 production, other strain types including ST23, ST17, ST76 and ST45 were associated with NDM production. Further research is needed to understand the adaptability of plasmids encoding different carbapnemases in different strain types of K. pneumoniae. Similar to the case of K. pneumoniae among which ST11 was the major strain type, a major strain type of carbapenemase-producing E. coli was also identified. ST131 of CREC was found to be a major strain type in both China and other countries. Consistent with reports in other parts of the world (Cai et al., 2014; Naas et al., 2011; Ortega et al., 2016), ST131 in this study was also closely associated with KPC-2 production. However, it should be noted that ST131 type E. coli were more commonly detected in Beijing and Zhejiang province where signs of clonal spread were evident, whereas it was less common in other parts of the country. In contrast, ST167 and ST410 seem to be of more clinically relevant since they are not only widely disseminated in China but are also the major blaNDM-bearing strains. Further dissemination of these types of carbapenem-resistant E. coli may become a significant problem in clinical settings in China. Variation between the prevalence rate of CRE among different locations was obvious. The unique pattern of distribution CRE and carbapenemase genes may suggest that clonal spread in specific region is common.