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Carbapenem Resistance

The Enterobacteriaceae are a large family of gram-negative bacilli that includes Escherichia coli, Klebsiella species, and Enterobacter species. They are normal inhabitants of the gastrointestinal tract of humans and animals and a common cause of community-acquired and health-care–acquired infections.  They have gradually developed resistance to broad spectrum antibiotics. In the United States, these resistant strains have been treated with carbapenem antibiotics including imipenem, meropenem, doripenem, and ertapenem.  However, a new class of beta-lactamase enzymes that hydrolyze & inactivate the carbapenems is being detected in the United States. These carbapenemases are usually plasmid-mediated, which facilitates transfer between bacteria. Carbapenem-resistant Enterobacteriaceae (CRE) were uncommon in the United States before 2000, but have increased in hospitals over the past 13 years. In 2012, 3.9% of acute-care short stay hospitals and 17.8% of long-term acute-care hospitals reported at least one CRE HAI.  Klebsiella species accounted for most of this increase (MMWR, March 8, 2013, 62(09);165-170). Invasive bloodstream infections with CRE have mortality rates as high as 50%. Therefore, they have become a serious infection control concern.

The most common carpabenemase to date is found in Klebsiella pneumoniae, and is hence referred to as KPC. Other enteric bacteria in which this type of plamid-mediated carbapenemase has been reported include E. coli, K. oxytoca, S. marcescens, E. cloacae, E. aerogenes, C. freundii, and Salmonella.  Klebsiella pneumoniae carbapenemase (KPC), is encoded by a highly transmissible gene that has now spread widely throughout the United States and around the world. In addition to KPC, other carbapenemases have emerged among Enterobacteriaceae outside the United States.  The best known example is the New Delhi metallo-beta-lactamase (NDM). The unfortunate clinical significance of the carbapenemase-producing organisms is that they are usually resistant to most other anti-microbials, including all classes of beta-lactam agents, and often aminoglycosides and quinolones as well.

Centers for Disease Control (CDC) & Clinical Laboratory Standards Insitute (CLSI) have issued recommendations for the detection of carpabenemases. Some gram-negative organisms producing this enzyme may fall within the susceptible range for carbapenems by automated test systems, but will exhibit an elevated MIC to carbapenems. When these organisms are also resistant to a 3rd-generation cephalosporin, such as ceftriaxone, additional testing for carbapenemase production should be performed. This confirmatory testing is called the Modified Hodge Test. Organisms tested by this method are reported as positive or negative for carbapenemase production. All carbapenems will be reported as resistant when an organism tests positive. Carbapenem resistance of the NDM-1 type is detected by standard susceptibility test methods. Enteric organisms suspicious for NDM-1 would be forwarded to the CDC for confirmation. 

Current CRE prevention strategies are based on the identification of patients colonized or infected with CRE.  Contact precautions are implemented for those patients harboring CRE.


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