Thirty-nine bla KPC -producing isolates of the family Enterobacteriaceae with carbapenem resistance or reduced carbapenem susceptibility were obtained from inpatients from eight hospitals in six cities of three provinces in eastern China. The pulsed-field gel electrophoresis analysis of all 36 Klebsiella pneumoniae isolates revealed six major patterns. The resistant plasmids of most isolates were successfully transferred by conjugation and evaluated experimentally to be 40 to 180 kb in size. A 20.2-kb bla KPC -surrounding nucleotide sequence from plasmid pKP048 has been obtained and contains an integration structure of a Tn3-based transposon and partial Tn4401 segment, with the gene order Tn3-transposase, Tn3-resolvase, ISKpn8, the bla KPC-2 gene, and the ISKpn6-like element. The chimera of several transposon-associated elements indicated a novel genetic environment of the K. pneumoniae carbapenemase -lactamase gene in isolates from China.Carbapenems often are used as the most appropriate agents in the treatment of infections caused by multiresistant gramnegative bacteria. However, reports of carbapenem-hydrolyzing enzymes have become increasingly frequent, and the most common carbapenemases to emerge in recent years have been the Klebsiella pneumoniae carbapenemases (KPCs) (8). The KPC-producing isolates of Pseudomonas aeruginosa and Pseudomonas putida also were reported recently (1, 30). The geographical distribution of bla KPC -producing isolates has widened not only within the United States, including the New York City region (2, 4, 5, 33), Pennsylvania, Ohio, Delaware, and Arkansas (8, 24), but also in Israel (22), France (21), Greece (7), Colombia (31), China (32), and recently in Argentina (23), Brazil (19), and the United Kingdom (34).Whereas the KPC enzymes in novel locations are reported increasingly worldwide, very little information is known about the genetic elements around this resistance gene. Naas et al. characterized a new transposon-related structure named Tn4401, which mediated KPC -lactamase mobilization in several bla KPC -positive K. pneumoniae and P. aeruginosa strains isolated from the United States, Colombia, and Greece (20). This transposon seems to be responsible for rapid bla KPC spread. Another finding for the bla KPC -surrounding structure was the KQ element, which is a large composite element consisting of a Tn1331 backbone and a Tn4401-like element and qnrB19 insertion (25). However, in China, the genetic environment of bla KPC genes is unclear. The aim of this study was to characterize the detailed genetic environment surrounding the bla KPC gene and report the emergence of bla KPC-2 -producing Enterobacteriaceae, including K. pneumoniae, Citrobacter freundii, Klebsiella oxytoca, and Enterobacter cloacae isolates from several hospitals in eastern China.
MATERIALS AND METHODSBacterial isolates. Thirty-nine nonduplicated isolates of the family Enterobacteriaceae (36 K. pneumoniae, 1 C. freundii, 1 K. oxytoca, and 1 E. cloacae isolate) with carbapenem resistance or reduced carbape...