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


Antimicrobial drug susceptibility data were obtained from The Surveillance Network (TSN) database-USA (Eurofin-Medinet, Herndon, VA, USA). This database has been used to characterize national antimicrobial drug susceptibility trends.[14,17–19] The network includes ≈300 clinical microbiology laboratories that serve one or more patient care facilities. Laboratories included in the network were selected to be representative of hospitals in each of the 9 US Census Bureau regional divisions. To be included in the TSN database, the laboratories must submit results from all routine antimicrobial drug susceptibility testing performed on site. Categorical result interpretations are based on the Clinical Laboratory Standards Institute ( criteria adopted by the reporting facilities at the time of testing and reflect susceptibilities as reported to clinicians. The data are electronically validated and merged into a central TSN database.

The database includes records with the following information: identified organism; tested drug and susceptibility result: susceptible, intermediate resistance, or resistant; source of the isolate: blood, urine, wound, lower respiratory tract, or other (upper respiratory tract and skin cultures); patient characteristics: age, sex; the health care setting where the patient sample was collected: outpatient (ambulatory), inpatient intensive care unit (ICU), inpatient (non-ICU), and long-term care settings; the geographic location of the laboratory where the specimen was tested; and the date of the drug susceptibility test.

Our analysis considered relevant isolates obtained from all children (age range 1–17 years) in outpatient (ambulatory), inpatient ICU, inpatient non-ICU, and long-term care settings during January 1, 1999-June 30, 2012. The included pathogens were Escherichia coli, K. pneumoniae, Proteus mirabilis, Enterobacter cloacae, E. aerogenes, Citrobacter freundii, C. koseri, and Serratia marcescens. K. oxytoca and Providencia species were not included in the TSN database. A separate analysis was performed on isolates from infants (age <1 year) because data were only available from 2010 onwards.

We defined the CRE phenotype by using CDC criteria to include relevant isolates that were resistant to all third-generation cephalosporins (ceftriaxone, cefotaxime, or ceftazidime), and nonsusceptible to ≥1 carbapenem (ertapenem, meropenem, imipenem, or doripenem).[20] Isolates that were not tested against all 3 third-generation cephalosporins were still classified as CRE if they were resistant against all tested third-generation cephalosporins. For bacteria with intrinsic imipenem nonsusceptibility (P. mirabilis, Providencia spp.), the CRE criteria required nonsusceptibility to meropenem, doripenem, or ertapenem.[20]

Data were filtered to retain isolates that were tested against ≥1 third-generation cephalosporin and ≥1 carbapenem of those considered for the CRE phenotype. When duplicate records (with same identification number, drug susceptibility test, and source location) existed, the first record was kept and the other records were discarded. The frequency of the CRE phenotype is reported as the proportion of positive isolates of all tested isolates included in the analysis. Individual susceptibility results were stratified by location (ICU, inpatient non-ICU, and outpatient); patient age (1–5, 6–12, and 13–17 years); patient sex, isolate source (blood, urine, wound, lower respiratory tract, and other); 2-year intervals; and geographic region on the basis of the location of the laboratory (West, Northeast, South Atlantic, South Central, East North Central, and West North Central). These 6 regions correspond to the 4 US Census regions (West, Northeast, South, Midwest). The South and Midwest regions were split (into South Central and South Atlantic, and East and West North Central, respectively) to achieve a more even regional distribution of isolates.

The χ2 (Cochran-Armitage) test for linear trend was used to test the significance of 2-year trends. A quadratic term was added to test for a nonlinear shape of the trend. If the parameter estimate for the square of the time variable was significant and positive (negative) (p<0.05), that implied that the trend was nonlinear and the frequency of resistance was changing at an increasing (decreasing) rate. Susceptibility patterns of CRE isolates to other antimicrobial drugs were also assessed. Data were analyzed by using the R statistical software environment.[21]