Carbapenem-resistant Enterobacteriaceae in Children

United States, 1999-2012

Latania K. Logan; John P. Renschler; Sumanth Gandra; Robert A. Weinstein; Ramanan Laxminarayan


Emerging Infectious Diseases. 2015;21(11):2014-2021. 

In This Article

Abstract and Introduction


The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections is increasing in the United States. However, few studies have addressed their epidemiology in children. To phenotypically identify CRE isolates cultured from patients 1–17 years of age, we used antimicrobial susceptibilities of Enterobacteriaceae reported to 300 laboratories participating in The Surveillance Network–USA database during January 1999–July 2012. Of 316,253 isolates analyzed, 266 (0.08%) were identified as CRE. CRE infection rate increases were highest for Enterobacter species, blood culture isolates, and isolates from intensive care units, increasing from 0.0% in 1999–2000 to 5.2%, 4.5%, and 3.2%, respectively, in 2011–2012. CRE occurrence in children is increasing but remains low and is less common than that for extended-spectrum β-lactamase–producing Enterobacteriaceae. The molecular characterization of CRE isolates from children and clinical epidemiology of infection are essential for development of effective prevention strategies.


Gram-negative bacteria belonging to the family Enterobacteriaceae are major causes of health care-acquired and community-acquired infections. In the past 3 decades, antimicrobial drug resistance in this family of bacteria has increased dramatically, specifically because of enzymes that hydrolyze broad-spectrum β-lactam antimicrobial drugs.[1,2] Genes encoding AmpC cephalosporinases (AmpC) may be chromosomal or plasmid-based in origin, whereas genes encoding extended-spectrum β-lactamases (ESBLs) are most often carried on mobile genetic elements, such as plasmids or transposons, and cause resistance to all β-lactams except carbapenems and cephamycins.[1–4] However, ESBLs and AmpC can confer carbapenem resistance when associated with alteration or loss of porins, a family of proteins on the outer membrane of gram-negative bacteria.[2,5]

In recent years, the rapid global spread of carbapenem-resistant Enterobacteriaceae (CRE) has been facilitated by mobile genetic elements harboring genes encoding for carbapenemases, such as Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases.[6,7] More recently, oxacillinase 48 (OXA-48)–producing Enterobacteriaceae have emerged in the United States, adding to major increases in CRE infections.[8] Carbapenem-resistant organisms often carry additional plasmid-borne genes against other antimicrobial drug classes, rendering them multidrug resistant (MDR).

Few, if any, antimicrobial drugs are able to treat these infections, and their prevalence is increasing in the United States, including in children.[9] The National Healthcare Safety Network of the US Centers for Disease Control and Prevention (CDC) reported that the proportion of Enterobacteriaceae that were carbapenem-resistant increased from 1.2% in 2001 to 4.2% in 2011, and that in 2012, 4.6% of acute-care hospitals reported ≥1 CRE hospital-acquired infection.[10] In a 2013 Threat Report on Antimicrobial Resistance, the CDC prioritized CRE as an urgent threat (the highest level), requiring concerted commitment and action, and noted that ≈50% of hospitalized patients with bloodstream infection caused by CRE die from the infection.[10,11]

Despite this increased attention for CRE in the United States,[6,12–14] limited data are available on the epidemiology of these infections in children.[9,15,16] In this study, our primary objective was to describe the national and regional epidemiology of CRE in children in the United States.