Carbapenem-Resistant Enterobacteriaceae in Children, United States, 1999-2012

Abstract

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.

Keywords: CRE; Surveillance Network–USA database; United States; antibacterial agents; antimicrobial resistance; bacteria; carbapenem-resistant Enterobacteriaceae; children; epidemiology; infections; β-lactamases.

Figure 1

National trends in prevalence of carbapenem-resistant Enterobacteriaceae (CRE) isolates from children, The Surveillance Network−USA database, 1999–2012. Markers show the percentage of isolates that belonged to the resistance phenotype for each 2-year period. Data for patients <1 year of age were not available for all years and were excluded from this analysis. The All Organisms trend encompasses Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, E. aerogenes, Citrobacter freundii, C. koseri, and Serratia marcescens. Each trend had a significant positive quadratic term: All Organisms (p = 1.3 × 10⁻⁴⁰), E. aerogenes and E. cloacae (p = 1.4 × 10⁻²⁹), K. pneumoniae (p = 6.6 × 10⁻¹¹), and E. coli (p = 2.4 × 10⁻¹¹). Trends for C. freundii and C. koseri, S. marcescens, and P. mirabilis are not shown but they all had significant positive quadratic terms (p = 0.0006; p = 0.002; and p = 1.0 × 10⁻⁷).

Figure 2

Prevalence of carbapenem-resistant Enterobacteriaceae (CRE) isolates from children by health care setting, The Surveillance Network-USA database, 1999–2012. Health care setting was determined by patient location at the time a microbiological sample was collected. Data for patients <1 year of age were not available for all years and were excluded from this analysis. There was a significant positive quadratic trend for intensive care unit (ICU) (p = 1.1 × 10⁻¹⁸), outpatient (p = 8.6 × 10⁻²⁶), and inpatient non-ICU (p = 5.0 × 10⁻¹¹). There was no significant trend for the nursing home setting, which made up 0.34% of total isolates (Table 1).

Figure 3

Regional trends in the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) isolates from children, The Surveillance Network−USA database, 1999–2012. A) Percentage of isolates with CRE phenotype, 1999–2006 (0%). The 6 regions shown correspond to the 4 US Census regions (West, Northeast, South, Midwest). However, the Midwest and South regions, respectively, were split into East and West North Central and South Central and South Atlantic. Isolates from Alaska and Hawaii are included in the West region. B–D) Percentage of isolates with CRE phenotype, by 2-year period, 2007–2012. There was a significant positive quadratic trend for West (p = 4.1 × 10⁻¹⁵), South Atlantic (p = 9.4 × 10⁻¹²), East North Central (p = 0.0002), South Central (p = 5.2 × 10⁻¹⁷), and West North Central (p = 7.2 × 10⁻⁸). There was a significant linear trend for North East (p = 5.8 × 10⁻⁸). Data for patients <1 year of age were not available for all years and were excluded from this analysis.