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Analysis of β-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey
Latania K Logan1, Andrea M Hujer2, Steven H Marshall3
1Department 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.
Insights
Multidrug-resistant infections in children are rising, with most pediatric Enterobacteriaceae isolates carrying resistance genes. Understanding these diverse resistance mechanisms is crucial for public health.
Area of Science:
- Pediatric Infectious Diseases
- Antimicrobial Resistance
- Molecular Epidemiology
Background:
- Multidrug-resistant (MDR) Enterobacteriaceae infections are an increasing concern in U.S. children.
- There is limited multicentered data on the antibiotic resistance genes driving MDR phenotypes in pediatric Enterobacteriaceae.
Purpose of the Study:
- To analyze the antibiotic resistance genes responsible for MDR phenotypes in pediatric Enterobacteriaceae isolates.
- To characterize the molecular epidemiology of these resistant isolates in a U.S. pediatric population.
Main Methods:
- Analysis of 225 pediatric Enterobacteriaceae isolates (ages 0-18) exhibiting extended-spectrum β-lactamase (ESBL) or carbapenemase phenotypes.
- Utilized DNA microarrays for detecting β-lactamase genes (ESBL, plasmid-mediated AmpC [pAmpC], carbapenemase).
- Employed repetitive-sequence-based PCR, multilocus sequence typing (MLST), and plasmid replicon typing for isolate and plasmid characterization.
Main Results:
- 90.7% of isolates contained a β-lactamase (bla) gene; blaCTX-M-1 group was most common (49.8%).
- Carbapenem resistance was observed in 1.8% of isolates (blaKPC, blaIMP).
- pAmpC genes (blaACT/MIR, blaCMY) were present in 14.2%; predominant E. coli (phylogenetic group B2) carried blaCTX-M-1 and specific plasmid types.
Conclusions:
- Pediatric β-lactam resistance in Enterobacteriaceae is diverse, with distinct mechanisms compared to adults.
- Specific molecular types and plasmid elements are associated with resistance genes in pediatric isolates.
- Further research is needed to understand the impact and dissemination of MDR Enterobacteriaceae in children.
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.