The dominant clone of KPC-producing K. pneumoniae in China is ST11, which is closely related to ST258, which has been reported worldwide.

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...

A carbapenem-resistant isolate of Klebsiella pneumoniae producing class A carbapenemase KPC-2 was identified in Zhejiang, China. The KPC-2 gene was located on an approximately 60-kb plasmid in a genetic environment partially different from that of bla KPC-2 in the isolates from the United States and Colombia.

Objectives: The aim was to investigate the activity of ceftazidime/avibactam (CAZ/AVI) against carbapenem-resistant Klebsiella pneumoniae (CRKP) and identify the resistance mechanisms before CAZ/ AVI coming to Chinese market. Methods: Clinical CRKP isolates were continuously collected from 36 tertiary hospitals in China from 1 March 2017 to 31 July 2017. CAZ/AVI MICs were determined by agar dilution method. CAZ/AVI resistant isolates were submitted to whole genome sequencing. The copy number and relative expression of bla KPC were determined by quantitative PCR. Results: A total of 872 CRKP isolates were collected, and MIC 50 and MIC 90 of CAZ/AVI were 4 and 8 mg/L. The resistant rate of CAZ/AVI was 3.7% (32/872). Among the resistant isolates, 53.1% (17/32) were metallo-b-lactamase-producing K. pneumoniae (MBL-KP), 40.6% (13/32) were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) and 6.3% (2/32) produced both MBL and KPC. One of the KPC-KP with high level CAZ/AVI resistance (>128 mg/L) harboured mutated bla KPC-2 (D179Y). In 12 wild-type bla KPC-2 isolates, the relative copy number and expression of bla KPC-2 gene were 2.5-fold and 2.7-fold higher than that in the CAZ/AVI MIC 0.5 mg/L group (p < 0.05), and when added avibactam at a fixed concentration of 8 mg/L, 91.7% (11/12) isolates could restore susceptibility. Conclusions: Resistance against CAZ/AVI in CRKP emerged before clinical use of CAZ/AVI in China, although most of the CRKP isolates maintained the susceptibility. MBL production, bla KPC-2 point mutation and high KPC expression played an important role in CAZ/AVI resistance.