Clinical and Genetic Characteristics of Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae Among Canadian Children
Bibliographic record
Abstract
Background: Infections with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) in nonoutbreak settings have not demonstrated the presence of dominant strains. Our objective was to determine the incidence, clinical characteristics, and genetic characteristics of ESBL-E infections among a group of Canadian children. Methods: From 2012 through 2017, patients aged ≤18 years with first-episode ESBL-E infections who presented at a pediatric center were reviewed. All clinical isolates were phenotypically identified in the laboratory as ESBL-producers. Demographic and clinical data were collected, including comorbid conditions, presence of devices, and previous antibacterial exposure. Community-associated infection was defined as a positive culture from a sterile site within the first 48 hours of hospital admission and no healthcare exposure during the preceding year. Isolates were sent to the Public Health Ontario Laboratory for whole-genome sequencing. Multilocus sequence typing was used to determine clonal relationship. Results: During the study period, 102 patients were identified with first-episode ESBL-E infection, and the proportion of ESBL-E isolates among all clinical isolates of E. coli and Klebsiella spp increased from 0.6% to 2.6% between 2012 and 2017, respectively (P = .001). The median age was 1 year (interquartile range, 0.8–5 years). Women comprised 66% of cases. No comorbid conditions were noted among 58 patients (57%), and 24% had previous antibiotic exposure, most frequently a cephalosporin (16%). ESBL-E was most frequently isolated in the urine (91%) and least frequently in the blood (2.2%) and was predominantly Escherichia coli (90%). Infection was most frequently diagnosed in the outpatient setting (61%); there were 11 healthcare-associated infections. Whole-genome sequencing of ESBL-E isolates revealed predominance of blaCTX-M-15 (63 isolates, 62%) and blaCTX-M-27 (16%) genes, and sequence type (ST) 131 (41%). Mutations conferring fluoroquinolone nonsusceptibility were noted among 62 isolates (61%), most frequently associated with ST131 (38 of 62 isolates, 61%) and among all 5 isolates with ST1193, an emerging multidrug-resistant E. coli clone. In addition, 15 patients had recurrence of ESBL-E infection at median of 113 days (IQR, 26–208); blaCTX-M-27 was found in 33% of recurrent infections compared to 12% of primary infections (P = 0.045). Conclusions: This study is the first in Canada to provide whole-genome sequencing data regarding ESBL-E in a pediatric population. The gene blaCTX-M-15 and ST131 clone were predominant. More than 60% of infections were community associated and demonstrated cross resistance to fluoroquinolones. With 76% of infections in antibiotic-naïve children, ESBL-E is a public health concern, and a One Health approach is critical to understanding the epidemiology and curbing the spread of multidrug-resistant Enterobacteriaceae. Funding: None Disclosures: None
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".