Carbapenem-Resistant Enterobacteriaceae an Increasing Threat in the United States

By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Hospital Epidemiologist, Sequoia Hospital, Redwood City, CA, Editor of Infectious Disease Alert.

Synopsis: The frequency of isolation of carbapenem-resistant enterobacteriaceae is increasing in the U.S., with the highest prevalence in the northeastern region.

Source: Centers for Disease Control and Prevention. Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR 2013;62:165-70.

The emergence of resistance in Enterobacteriaceae to ertapenem, imipenem, meropenem, and doripenem due to the production of a carbapenemase is occurring in two primary enzyme groups. One group, also classified within Ambler Class B, is called metalo — lactamases because of a requirement for zinc for their catalytic activity. These metalloenzymes remain rare in the U.S., but are prevalent in a number of other countries -- the New Delhi metallocarbapenemase (NDM) is a recently emerged example. Another group of carbapenemases, termed serine proteases because of the presence of this amino acid within their catalytic site, belong to Ambler Classes A, C, and D. One of these, KPC, first emerged in Klebsiella pneunoniae (hence the name, standing for K. pneumoniae carbapenemase), but has since spread via plasmids to other members of the Enterobacteriaceae. KPC-producing bacteria first emerged in the U.S. and are becoming increasingly prevalent both here and in other countries in which it has appeared.


The CDC has now assessed the extent of the problem of carbapenem-resistant Enterobacteriaceae (CRE) in the U.S. Among almost 4000 acute care hospitals that performed surveillance for either catheter-associated urinary tract infections or central line-associated blood stream infections during the first 6 months of 2012, 181 (4.6%) reported at least one CRE infection. This represented an approximate 4-fold increase in the last 10 years. CRE were reported by 3.9% of short-stay and 17.8% of long-term acute-care hospitals. The prevalence ranged from 3.2%-3.6% in the Midwest, South and West to 9.6% of hospitals in the Northeast. Klebsiella species were most frequently affected, followed by Enterobacter species and by Escherichia coli. In 2011, 4.2% of Enterobacteriaceae were carbapenem-resistant.

As pointed out in the CDC document, invasive infections, such as blood stream infection are associated with high mortality. Furthermore, CRE often contain multiple resistance mechanisms in addition to carbapenemases, making treatment of infections due to them highly problematic. They may rapidly spread within hospitals, where they are most prevalent.

The CDC has published extensive recommendations for control of CRE, including 8 core measures.1 These are:

  • Hand hygiene adherence with monitoring and feedback
  • Contact precautions
  • Healthcare personnel education
  • Minimization of device (e.g., vascular access devices, endotracheal tubes, urinary catheters) utilization
  • Patient and staff cohorting
  • Procedures for rapid notification of appropriate personnel by the laboratory
  • Antimicrobial stewardship
  • Screening for CRE colonization

For hospitals that rarely or have never previously identified a CRE2, they recommend contact isolation in a single room, reinforcement of hand hygiene, and education of staff about prevention measures. They further recommend screening of epidemiologically-linked patient contacts with, at a minimum, stool, rectal or perirectal cultures. Consideration may be given to a point-prevalence study of the affected unit, as well as to preemptive contact precautions. If additional colonizations/infections are detected, consideration may be given to cohorting patients and staff.


  1. CDC. 2012 CRE Toolkit- Guidance for Control of Carbapenem-Resistant Enterobacteriaceae (CRE). Part 1: Facility-level CRE Prevention.
  2. CDC. 2012 CRE Toolkit- Guidance for Control of Carbapenem-Resistant Enterobacteriaceae (CRE). Appendix B: General Approach to Carbapenem-resistant Enterobacteriaceae (CRE) Control in Facilities that Rarely or Have Not Identified CRE.