title: Analysis of β-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey.
abstract: Multidrug-resistant (MDR) Enterobacteriaceae infections are increasing in U.S. children; however, there is a paucity of multicentered analyses of antibiotic resistance genes responsible for MDR phenotypes among pediatric Enterobacteriaceae isolates. In this study, 225 isolates phenotypically identified as extended-spectrum β-lactamase (ESBL) or carbapenemase producers, recovered from children ages 0 to 18 years hospitalized between January 2011 and April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type β-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence typing (MLST) were performed to assess isolate similarity. Plasmid replicon typing was conducted to classify plasmids. The median patient age was 4.2 years, 56% were female, and 44% presented in the outpatient setting. The majority (60.9%) of isolates were Escherichia coli and from urinary sources (69.8%). Of 225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7% contained a bla gene. The most common genotype was the blaCTX-M-1 group (49.8%); 1.8% were carbapenem-resistant Enterobacteriaceae (three blaKPC and one blaIMP). Overall, pAmpC (blaACT/MIR and blaCMY) were present in 14.2%. The predominant E. coli phylogenetic group was the virulent B2 group (67.6%) associated with ST43/ST131 (Pasteur/Achtman MLST scheme) containing the blaCTX-M-1 group (84%), and plasmid replicon types FIA, FII, and FIB. K. pneumoniae harboring blaKPC were non-ST258 with replicon types I1 and A/C. Enterobacter spp. carrying blaACT/MIR contained plasmid replicon FIIA. We found that β-lactam resistance in children is diverse and that certain resistance mechanisms differ from known circulating genotypes in adults in an endemic area. The potential impact of complex molecular types and the silent dissemination of MDR Enterobacteriaceae in a vulnerable population needs to be studied further.
authors.affiliation: Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA latania_logan@rush.edu.
authors.forename: Latania K
authors.initials: LK
authors.lastname: Logan
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Hujer
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Marshall
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: T Nicholas
authors.initials: TN
authors.lastname: Domitrovic
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Rudin
authors.affiliation: Department of Microbiology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pediatrics, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: Nadia K
authors.initials: NK
authors.lastname: Qureshi
authors.affiliation: Departments of Medicine and Pathology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Hayden
authors.affiliation: Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Scaggs
authors.affiliation: Department of Pediatrics, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Karadkhele
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Department of Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA Departments of Molecular Biology and Microbiology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002641:Chicago / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; C063912:carbapenemase