Affiliations: 1. Division of Infectious Diseases, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; and Epidemiology and Infection Prevention, Johns Hopkins Health System, Baltimore, Maryland; 2. Division of Medical Microbiology, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland; 3. Prevention and Health Promotion Administration, Infectious Disease Bureau, Maryland Department of Health and Mental Hygiene, Baltimore, Maryland. Received September 7, 2012; accepted February 16, 2013; electronically published May 22, 2013. 2013 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2013/3407-0011$15.00. DOI: 10.1086/671003 b-lactamase production is the most important resistance mechanism among gram-negative bacteria. The evolution of these enzymes has been driven by excessive antimicrobial use and pressure. Following the introduction of broad-spectrum cephalosporins, the first plasmid-encoded extended-spectrum b-lactamase (ESBL, an enzyme that can hydrolyze third-generation cephalosporins and aztreonam yet is inhibited by clavulanic acid) was described in Germany in 1983; the first report in the United States occurred in 1988. As a result of this resistance, carbapenem antibiotic use increased. The first Enterobacteriaceae isolates resistant to a carbapenem, mediated through chromosomally encoded carbapenemases, were described in the 1980s. In 1996, the first plasmid-mediated carbapenemase emerged in the United States, identified in a carbapenem-resistant Klebsiella pneumoniae. A b-lactamase gene, blaKPC1, identified in the strain, encoded the enzyme Klebsiella pneumoniae carbapenemase-1 (KPC-1). Dissemination of KPCs was likely facilitated by the encoding of blaKPC on a transposon structure (Tn4401) capable of inserting on different plasmids. Currently, 14 different KPC enzymes have been described (KPC-2–15; http://www.lahey.org/Studies /other.asp#table1, accessed February 2, 2013). Two metallo-b-lactamases (MBLs), VIM and IMP (for “active on imipenem”), initially described in Pseudomonas sp. likely conjugated and emerged in Enterobacteriaceae. More recently, another carbapenemase belonging to Ambler class B b-lactamases was described in India, Pakistan, and the United Kingdom and was named NDM-1. Since the initial description, 6 more NDM enzymes have been characterized (http://www.lahey.org/Studies/other.asp#table1; accessed February 2, 2013). Now that carbapenemases, mediated by a variety of molecular mechanisms (molecular classes A, B, or D), have been described in multiple Enterobacteriaceae species, these resistant organisms are now collectively referred to as carbapenemase-producing Enterobacteriaceae (CPE) for infection prevention and antimicrobial stewardship purposes. We use the term “CPE” here to represent any Enterobacteriaceae producing KPC, VIM, IMP, or NDM.