title: Pediatric carbapenem-resistant Enterobacteriaceae in Los Angeles, California, a high-prevalence region in the United States.
abstract: 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.
authors.affiliation: 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.
authors.forename: Pia S
authors.initials: PS
authors.lastname: Pannaraj
authors.forename: Jennifer Dien
authors.initials: JD
authors.lastname: Bard
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerini
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Weissman
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004755:Enterobacteriaceae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000473:pathology; D004926:Escherichia coli; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007711:Klebsiella pneumoniae; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D062606:Tertiary Care Centers; D055815:Young Adult; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
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