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

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms (MDRO) 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; control 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, two were unrelated, non-ST258 KP strains harboring bla(KPC-2), one was a ST258 KP harboring bla(KPC-3), and the last was an E. coli containing bla(KPC-2). KPC-CRE and CSE-infected patients had more MDRO infections, long-term care facility admissions, and lengths of stay (LOS) >7 days before culture. KPC-CRE and CSE patients had more gastrointestinal (GI) comorbidities (ORs 28.0 and 6.4) and ≥3 comorbidities (ORs 15.4 and 3.5) compared to 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 to 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.