Diversity of K. pneumoniae That Produce KPC | CDC EID

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Volume 16, Number 9–September 2010
Research
Worldwide Diversity of Klebsiella pneumoniae That Produce β-Lactamase blaKPC-2 Gene1
Gaëlle Cuzon, Thierry Naas , HaVy Truong, Maria-Virginia Villegas, Karin T. Wisell, Yehuda Carmeli, Ana. C. Gales, Shiri Navon-Venezia, John P. Quinn, and Patrice Nordmann
Author affiliations: Institut National de la Santé et de la Recherche Médicale, Paris, France (G. Cuzon, T. Naas, H. Truong, P. Nordmann); International Center for Medical Research and Training, Cali, Colombia (M.V. Villegas); Swedish Institute for Infectious Disease Control, Stockholm, Sweden (K.T. Wisell); Sourasky Medical Center, Tel Aviv, Israel (Y. Carmeli, S. Navon-Venezia); Universidade Federal de São Paulo, São Paulo, Brazil (A.C. Gales); John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois, USA (J.P. Quinn); and Chicago Infectious Disease Research Institute, Chicago (J.P. Quinn)

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Abstract
Klebsiella pneumoniaeisolates that produce carbapenemases (KPCs) are rapidly disseminating worldwide. To determine their genetic background, we investigated 16 blaKPC-2-harboring K. pneumoniae isolates from 5 countries. The isolates were multidrug resistant, possessed the blaKPC-2 gene, and differed by additional β-lactamase content. They harbored a naturally chromosome-encoded bla gene (blaSHV-1 [12.5%], blaSHV-11 [68.7%], or blaOKP-A/B [18.8%]) and several acquired and plasmid-encoded genes (blaTEM-1 [81.3%], blaCTX-M-2 [31.3%], blaCTX-M-12 [12.5%], blaCTX-M-15 [18.7%], and blaOXA-9 [37.5%]). The blaKPC-2 gene was always associated with 1 of the Tn4401 isoforms (a, b, or c). Tn4401 was inserted on different-sized plasmids that belonged to different incompatibility groups. Several blaKPC-containing K. pneumoniae clones were found: 9 different pulsotypes with 1 major (sequence type 258) and 7 minor distinct allelic profiles. Different clones harboring different plasmids but having identical genetic structure, Tn4401, could be at the origin of the worldwide spread of this emerging resistance gene.
Resistance of Klebsiella pneumoniae to carbapenems is mainly associated with acquired carbapenem-hydrolyzing β-lactamases (1). These β-lactamases can be metallo β-lactamases (IMP, VIM), expanded-spectrum oxacillinases (OXA-48), or Ambler class A enzymes (NMCA, IMI, SME, GES, and KPC) (1–4). The most common class A carbapenemases in K. pneumoniae are the K. pneumoniae carbapenemases (KPCs) (4). KPCs in carbapenem-resistant K. pneumoniae strains were first reported in 2001 in North Carolina (5), and until 2005, the geographic distribution of these enzymes in Enterobacteriaceae, including K. pneumoniae, was limited to the eastern part of the United States (5,6). Now, KPC-producing K. pneumoniae isolates are frequently identified among nosocomial pathogens (7). Recently, dissemination of a single major clone of KPC-producing K. pneumoniae (sequence type [ST] 258) in the eastern United States has been suggested (8). KPCs have been observed more rarely among other gram-negative rods such as Pseudomonas spp. (9,10).

Outside the United States, KPC-producing K. pneumoniae are also being reported more often. The first case of KPC-producing K. pneumoniae infection was reported in 2005 in France and had a US origin (11). The first outbreak of KPC-producing K. pneumoniae outside the United States was in Israel (12). In South America, dissemination of KPC-producing K. pneumoniae was initially reported in 2006 in Colombia (13) and then in Brazil and Argentina (14,15). KPC enzymes have also been identified in P. aeruginosa isolates from Colombia (16). In the People's Republic of China, KPC enzymes in several enterobacterial species are being increasingly reported (17). Finally, in Europe a few cases of KPC-producing K. pneumoniae infection have been described, but in Greece, outbreaks have occurred (18). In Europe, different variants of KPCs (KPC-2 and KPC-3) have been described; some patients carrying KPC-positive isolates had been transferred from the United States, Israel, or Greece (19–21).

Reports of this β-lactamase being found in novel locations are increasing worldwide, probably signaling active spread. The genetic element carrying the blaKPC-2 gene, Tn4401, was recently elucidated (22). Three isoforms of this Tn3-like transposon (a, b, and c) are known. Several other genetic environments of blaKPC gene have been described; other insertion sequences have been found upstream of the blaKPC gene (23,24). Nevertheless, the downstream sequences of the blaKPC gene matched perfectly with Tn4401, which suggests that these insertion sequences have been inserted into Tn4401.

Insertion sequences may play major roles in the evolution of Tn4401, but little information is available about the bacterial strains and the plasmids that may explain this rapid spread. Our goal, therefore, was to characterize the genetic background of several blaKPC-2- harboring K. pneumoniae isolates from various geographic origins.

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