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Pediatric Carbapenem-resistant Enterobacteriaceae in Los Angeles, California, a High-prevalence Region in the United States

Pannaraj, Pia S. MD, MPH*†; Bard, Jennifer Dien PhD†‡; Cerini, Chiara MD*; Weissman, Scott J. MD§

The Pediatric Infectious Disease Journal: January 2015 - Volume 34 - Issue 1 - p 11–16
doi: 10.1097/INF.0000000000000471
Original Studies

Background: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are on the rise worldwide but are not well described in pediatric populations. This study characterizes the clinical, phenotypic and genotypic characteristics of CRE infections at a free-standing US children’s hospital.

Methods: CRE were defined as any clinical Enterobacteriaceae isolate non-susceptible to either imipenem or meropenem and resistant to ceftriaxone, cefotaxime and ceftazidime determined by routine antimicrobial susceptibility testing. The modified Hodge test was performed to screen for the production of carbapenemase. Clinical data were reviewed, and molecular characterization of phylogenetic and resistance-associated traits was performed.

Results: CRE isolates were recovered from sterile and non-sterile sites in 10 patients, 6 weeks to 24 years of age, between 2011 and 2013. Co-morbidities included hematologic, genetic and urologic abnormalities. Two patients had traveled abroad (India, Lebanon) before CRE recovery. Carbapenemase determinants were detected in 5 cases, including KPC-3 in 2 Klebsiella pneumoniae (ST258 and ST18) and 1 Escherichia coli (ST131), and NDM-1 in 1 K. pneumoniae (ST37) and 1 E. coli (ST101) isolate. Additional resistance determinants were detected, including CTX-M-15, SHV-11, TEM-1, CMY-2, CMY-4 and CMY-42. Four patients died, including 2 of 3 patients with CRE bacteremia. There was no evidence of epidemiologic or molecular relatedness between any 2 cases.

Conclusions: This report documents the appearance of highly resistant Gram-negative pathogens in a vulnerable patient population at a pediatric tertiary referral center in a major US metropolitan area. Detailed understanding of the distribution and spread of CRE is essential for the timely detection and containment of these perilous pathogens.

Supplemental Digital Content is available in the text.

From the *Division of Infectious Diseases, Department of Pediatrics, Molecular Microbiology and Immunology, Children’s Hospital Los Angeles, Los Angeles, CA; Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Pathology, Children’s Hospital Los Angeles, Los Angeles, CA; and §Center for Global Infectious Disease Research, Seattle Children’s Hospital Research Institute and University of Washington, Seattle, WA.

Accepted for publication June 25, 2014.

S.W. has a patent application pending for a point-of-care diagnostic test to optimize the initial selection of antibiotics for urinary tract infections. The method remains in the developmental stage, and S.W. has received no financial compensation for or benefit from the patented entity. S.W. has also received grant funding from Pfizer to study Antimicrobial Stewardship Program effectiveness at US children’s hospitals. All other authors report no conflicts of interest.

Supported by NIH Grant Number 5 K23 HD072774-02 awarded to P.S.P.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Pia S. Pannaraj, MD, MPH, Children's Hospital Los Angeles, 4650 W. Sunset Blvd., MS#51, Los Angeles, CA 90027. E-mail:

© 2015 by Lippincott Williams & Wilkins, Inc.