Nationwide Surveillance of Clinical Carbapenem-resistant Enterobacteriaceae (CRE) Strains in China

Abstract

The increasing incidence of carbapenem-resistant Enterobacteriaceae (CRE) - mediated hospital infections in China prompted a need to investigate the genetic basis of emergence of such strains. A nationwide survey was conducted in China covering a total of 1105 CRE strains collected from 25 geographical locales with results showing that acquisition of two carbapenemase genes, bla_KPC-2 and bla_NDM, was responsible for phenotypic resistance in 90% of the CRE strains tested (58% and 32% respectively), among which several major strain types, such as ST11 of K. pneumoniae and ST131/ST167 of E. coli, were identified, suggesting that dissemination of specific resistant clones is mainly responsible for emergence of new CRE strains. Prevalence of the fosA3 gene which mediates fosfomycin resistance, was high, while the colistin resistance determinant mcr-1 was rarely present in these isolates. Consistently, the majority of the bla_NDM-bearing plasmids recoverable from the test strains belonged to IncX3, which contained a common core structure, bla_NDM-blaMBL-trpF. Likewise, the core structure of ISKpn27-bla_KPC-2-ISKpn2 was observed among plasmids harboring the bla_KPC-2 gene, although they were genetically more divergent. In conclusion, the increasing prevalence of CRE strains in China is attributed to dissemination of conservative mobile elements carrying bla_NDM or bla_KPC-2 on conjugative and non-conjugative plasmids.

Keywords: Carbapenem resistance; Enterobacteriaceae; Molecular epidemiology; Plasmid; bla(KPC-2); bla(NDM).

Fig. 1

Minimal spanning tree based on multi-locus sequence typing of carbapenem-resistant K. pneumoniae. Colored circles and numbers represent different sequence types that have been detected in this study; the size of the circle is proportional to the numbers of the strains belonging to each type.

Fig. 2

Minimal spanning tree based on multilocus sequence typing of carbapenem-resistant E. coli. Colored circles represent different sequence types; the size of the circle is proportional to the number of the strains belonging to each type.

Fig. 3

Carbapenem resistance rate and relative prevalence of various carbapenemase-producing elements among clinical carbapenem-resistant E. coli strains recovered from different provinces of China. Different background colors represent different rates of carbapenem resistance. Circle partitions represent the prevalence of different carbapenemases produced by carbapenem-resistant E. coli strains recovered from different locations. The resistance rate for each location was adopted from data of China Antimicrobial Resistance Surveillance Report (http://www.yiyimama.com/Sys/res/file/201512/20151220130152_4645_81ed026304834a5d81842924c78a1a9f_2014%E7%BB%86%E8%8F%8C%E8%80%90%E8%8D%AF%E7%9B%91%E6%B5%8B%E6%8A%A5%E5%91%8A.pdf; http://www.yiyimama.com/Sys/res/file/201512/20151220130134_7741_482f3b7ae95841998a37898e2ab2fa87_2015%E5%B9%B4%E7%9B%91%E6%B5%8B%E6%8A%A5%E5%91%8A.pdf).

Fig. 4

Carbapenem resistance rate and relative prevalence of various carbapenemase-producing elements among clinical carbapenem-resistant K. pneumoniae strains recovered from different provinces of China. Different background colors represent different prevalence levels of carbapenem resistance. Circle partitions represent the prevalence of different carbapenemases produced by carbapenem-resistant K. pneumoniae strains at different locations. The resistance rate for each location was adopted from data of China Antimicrobial Resistance Surveillance Report (http://www.yiyimama.com/Sys/res/file/201512/20151220130152_4645_81ed026304834a5d81842924c78a1a9f_2014%E7%BB%86%E8%8F%8C%E8%80%90%E8%8D%AF%E7%9B%91%E6%B5%8B%E6%8A%A5%E5%91%8A.pdf; http://www.yiyimama.com/Sys/res/file/201512/20151220130134_7741_482f3b7ae95841998a37898e2ab2fa87_2015%E5%B9%B4%E7%9B%91%E6%B5%8B%E6%8A%A5%E5%91%8A.pdf).

Fig. 5

Number of plasmids carrying diverse structures of bla_NDM-1-bearing mobile elements in conjugative plasmids harbored by carbapenemase-producing clinical K. pneumoniae and E. coli strains.

Fig. 6

Number of plasmids carrying diverse structures of bla_KPC-2-bearing mobile elements in conjugative plasmids harbored by carbapenemase-producing clinical K. pneumoniae and E. coli strains.