A Multicenter Case-Case–control Study of Factors Associated with Klebsiella pneumoniae Carbapenemase (KPC)-Producing Enterobacteriaceae (KPC-CRE) Infections in Children

BACKGROUND: KPC-CRE are multidrug-resistant organisms (MDRO) associated with morbidity and mortality worldwide. KPC-CRE infection prevalence is increasing in the pediatric population; however, multi-centered pediatric data are lacking. We sought to identify factors for KPC-CRE infections in children and to classify genotypes of infecting strains. METHODS: We conducted a case–case–control study of patients (0–22 years) at 3 tertiary care medical centers in Chicago, 2008–2015. Case group 1 were children identified with KPC-CRE infections; case group 2 possessed carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls (ctrls) were patients with completely negative cultures. Cases were matched to ctrls 1:1:3 by age, infection site, and hospital. Bivariate and stratified statistical analyses were performed. Molecular analysis was conducted on available isolates. RESULTS: We identified 18 KPC-CRE infections. Of 4 KPC-CRE available for molecular analysis, 3 were non-ST258 strains harboring bla(KPC-2); no strains were related. Median age of KPC-CRE patients 16 (1–22) years. Differences in race, gender, LOS, and mortality were not significant. KPC-CRE and CSE infected patients were more likely to have prior MDRO (KPC-CRE 95%, CSE 11%, Ctrl 0%), long-term care facility admission (KPC-CRE 21%, CSE 17%, Ctrl 0%), and LOS >7 days before culture. Both KPC-CRE and CSE more likely had gastrointestinal (GI) comorbidities (OR: 21.9, KPC-CRE; 6.9, CSE) and >3 comorbidities (OR: 12.0, KPC-CRE; 3.5, CSE) compared with ctrls; however only KPC-CRE patients had more pulmonary and neurologic comorbidities (ORs 5.4 and 4.6), or GI and pulmonary devices (ORs 9.3 and 5.3). Compared with ctrls, CSE patients more often had prior fluoroquinolone use (OR 7.4), while KPC-CRE patients were more likely exposed to carbapenems or aminoglycosides (ORs 9.1 and 7.1). CONCLUSION: In these children, factors associated with KPC-CRE infection reveal a high burden of disease and included pulmonary and neurologic comorbidities, GI and pulmonary devices, or exposure to carbapenems and aminoglycosides. Non-ST258 KPC-CRE strains were more common, and LOS and mortality rates were similar in all groups, which differs from adult reports. Control of CRE in children should focus on validating and mitigating these risk factors. DISCLOSURES: A. H. Bartlett, CVS Caremark: Consultant, Consulting fee; R. A. Bonomo, Merck: Grant Investigator, Research support; Allergan: Investigator, Research support; Wokhardt: Investigator, Research support; Glaxo Smith Kline: Investigator, Research support; Astra Zeneca: Investigator, Research support; Actavis: Speaker’s Bureau, Speaker honorarium