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Genetic transfer ability broadens CRKP threat
'The big one to worry about is E. coli'
Beyond the immediate threat to frail, hospitalized patients posed by emerging carbapenem-resistant Klebsiella pneumoniae (CRKP) is a larger concern: its mechanism of resistance is transferable to other bacterial species.
As a result, there is the possibility of transfer to Escherichia coli — another common resident of the human gut — making an infection that is already potentially deadly impervious to a completely new layer of antibiotics.
"The big one to worry about is E. coli, simply because it is such a common cause of infections both in the hospital and the community," says Arjun Srinivasan, MD, a medical epidemiologist in the CDC's division of health care quality promotion. "This plasmid that possesses the 'KPC' enzyme can be transferred to other types of bacteria. It has been well described for several different types of bacteria, mostly within that same family of Enterobacteriaeae organisms that live in the human gut."
The scenario is a familiar one. The first cases of vancomycin-resistant Staphylococcus aureus (VRSA) occurred in the United States due to transfer of resistance genes from vancomycin-resistant enterococci. The vancomycin-resistance determinant vanA, typically found in VRE but never in a clinical staph strain, was found in the VRSA isolates. While VRSA has not spread beyond the sporadically occurring cases, there always is concern that one of these genetic transfers may lead to broad proliferation of a highly resistant pathogen.
For CRKP, the most important mechanism of resistance is the production of a carbapenemase enzyme labeled blakpc, according to the CDC.1 The gene that encodes the enzyme is carried on a tranposon — a mobile piece of genetic material. If an organism receives this plasmid, it may become resistant to a wide array of antibiotics due to a "single genetic event," Srinivasan says. In addition to the carbapenems, the KPC enzyme confers resistance to all beta-lactams, including penicillin as well as the extended-spectrum cephalosporins, he says.
While primarily found in K. pneumoniae, the KPC enzyme has been reported in K. oxytoca, Citrobacter freundii, E. coli, and species varieties of Enterobacter, Salmonella, and Serratia. It also has been reported in Pseudomonas aeruginosa in the country of Colombia. The transfer of full resistance to a virulent strain of E. coli such as 0157 will certainly pass for a worst-case scenario until someone thinks of another one.
"One of the concerning aspects here is that this resistance mechanism is on a piece of genetic material that can move into other bacteria," Srinivasan says. "That raises the possibility that not only can the organism itself be transmitted from patient to patient, but this resistance mechanism can be transmitted from bacteria to bacteria and potentially allow for the creation of even more of these highly resistant pathogens.
Indeed, the genetic transfer factor also makes the CDC effort to contain CRKP a formidable challenge. "That resistant mechanism is going to [enable this] to disseminate more readily than something that is less likely to be transferable," says Mark Rupp, MD, an infectious disease physician at the University of Nebraska Medical Center in Omaha.