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A Multi-Centered Case-Case-Control Study of Factors Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults

Logan, Latania K., MD, MSPH*,†,‡,§; Nguyen, David C., MD*,¶,‖,**; Scaggs Huang, Felicia A., MD*,††; Qureshi, Nadia K., MD‡‡; Charnot-Katsikas, Angella, MD§§; Bartlett, Allison H., MD, MS¶¶; Zheng, Xiaotian, MD, PhD‖‖; Hujer, Andrea M., BS; Domitrovic, T. Nicholas, MS; Marshall, Steven H., MS; Bonomo, Robert A., MD‡,***; Weinstein, Robert A., MD†††,‡‡‡

The Pediatric Infectious Disease Journal: May 2019 - Volume 38 - Issue 5 - p 490–495
doi: 10.1097/INF.0000000000002176
Antimicrobial Reports

Background: Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population.

Methods: A case-case-control study of patients (0–22 years) at 3 tertiary-care Chicago-area medical centers, 2008–2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls had negative cultures. Case-control matching was 1:1:3 by age, infection site and hospital. Statistical and molecular analyses were performed.

Results: Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, 2 were unrelated, non-ST258 KP strains harboring blaKPC-2, one was a ST258 KP harboring blaKPC-3, and the last was an E. coli containing blaKPC-2. KPC-CRE and CSE-infected patients had more multidrug-resistant organisms infections, long-term care facility admissions and lengths of stay (LOS) > 7 days before culture. KPC-CRE and CSE patients had more gastrointestinal comorbidities (odds ratios [Ors], 28.0 and 6.4) and ≥ 3 comorbidities (Or 15.4 and 3.5) compared with controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs, 11.4 and 6.1). Compared with controls, CSE patients had more prior fluoroquinolone use (OR, 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs, 10.0 and 8.0). Race, gender, LOS and mortality differences were insignificant.

Conclusions: Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

From the *Department of Pediatrics

Section of Pediatric Infectious Diseases, Rush University Medical Center, Rush Medical College, Chicago, IL

Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, OH

§Department of Pediatrics, Cook County Health and Hospitals System, Chicago, IL

Department of Medicine, Rush University Medical Center, Rush Medical College, Chicago, IL

Department of Pediatrics, Division of Infectious Diseases

**Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH

††Department of Pediatrics, Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

‡‡Department of Pediatrics, Section of Pediatric Infectious Diseases, Loyola University Medical Center, Maywood, IL

§§Department of Pathology, The University of Chicago Medicine, Chicago, IL

¶¶Department of Pediatrics, Division of Pediatric Infectious Diseases, The University of Chicago Medicine, Chicago, IL

‖‖Department of Pathology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL

***Department of Medicine, Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western University, Cleveland, OH

†††Department of Medicine, Division of Infectious Diseases, Rush University Medical Center, Rush Medical College, Chicago, IL

‡‡‡Department of Medicine, Cook County Health and Hospital Systems, Chicago, IL.

Accepted for publication July 5, 2018.

Supported by National Institutes of Health - National Institute of Allergy and Infectious Diseases grant K08AI112506 (Dr. Logan) and grants R01AI072219, R01AI063517, and R01AI100560 (Dr. Bonomo). This work was also supported by the Department of Veterans Affairs Research and Development under award number I01BX001974, VISN 10 Geriatrics Research, Education and Clinical Center (Dr. Bonomo).

The authors have no funding or conflicts of interest to disclose.

Address for correspondence: Latania K. Logan, MD, MSPH, Rush University Medical Center 1653 W. Congress Parkway, Suite 951 Jelke, Chicago, IL 60612. E-mail:

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