A Multicenter Study of the Clinical and Molecular Epidemiology of TEM- and SHV-type Extended- Spectrum β-Lactamase producing (ESBL) Enterobacteriaceae (Ent) Infections in Children

Abstract

Background. ESBL Ent infections are increasingly prevalent in the pediatric population; however, most ESBL Ent studies have focused on adults and/or CTX-M-type strains. We sought to characterize the molecular epidemiology of ESBL Ent strains and to identify factors associated with TEM-and SHV-type ESBL Ent (TEMSHV Ent) infections in children. Methods. A case-control study of children (0-18 years) cared for by 3 Chicago hospitals during 2011-2016 was performed. Cases were 38 children with infections due to Ent harboring a lone TEM-or SHV-type ESBL as detected by DNA microarray (Check-Points). PCR, DNA sequencing, Rep-PCR, plasmid typing, and phylogenetic grouping were also performed. Controls (ctrls) were137 children with third-generation cephalosporin susceptible Ent infections matched by age and hospital. Demographics; patient residence; comorbidities; device, antibiotic, and healthcare exposures were evaluated. Bivariate and multivariable logistic regression analyses explored associations between predictors and TEMSHV Ent infection. Results. Of 38 TEMSHV Ent infections, 74% were SHV-type and 26% TEM-type. The median age of TEMSHV Ent patients was 4.3 (0-17.9) years. Predominant organisms were Klebsiella spp. (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Most strains were unrelated; 47% were MDRO. On bivariate analysis, TEMSHV Ent patients were more likely to be male (53% vs. 34%, P = 0.04), have longer LOS After infection (35d vs. 14d, P < 0.001) but no Difference in mortality, and have less UTIs (53% vs. 75%, P = 0.01) than ctrls. On multivariable analysis, children with TEMSHV Ent infections more ofen had recent inpatient care (OR 8.2), yet were diagnosed more frequently as outpatients (OR 25.6) and less ofen in NICUs (OR 0.036) than ctrls. TEMSHV Ent patients had more gastrointestinal (GI) (OR 23.7) and renal comorbidi-ties (OR 4.2) vs. ctrls. Differences in race, gender, residential neighborhood, antibiotic exposure, and foreign bodies were not significant After controlling for other factors. Conclusion. In children, factors associated with TEMSHV Ent infections include recent inpatient care and GI and renal comorbidities. Infections are associated with longer LOS but not greater mortality. Control of TEMSHV Ent infections in children should focus on validating and responding to these risk factors.