A Multicentered Study of the Clinical and Molecular Epidemiology of TEM- and SHV-type Extended-Spectrum Beta-Lactamase Producing Enterobacterales Infections in Children

Latania K. Logan*, Jared R. Rispens, Rachel L. Medernach, T. Nicholas Domitrovic, Andrea M. Hujer, Steven H. Marshall, Susan D. Rudin, Nadia K. Qureshi, Xiaotian Zheng, Mary K. Hayden, Robert A. Weinstein, Robert A. Bonomo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales-(Ent) infections are increasing in pediatrics. Before CTX-M ESBL emerged, the most common infection-associated ESBL genes were TEM and SHV-type ESBLs. We sought to define the current epidemiology of Ent infections in children due to blaTEMand blaSHV(TEM-SHV-Ent). Methods: A retrospective case-control analysis of children with TEM-SHV-Ent infections at 3 Chicago-area hospitals was performed. Cases had extended-spectrum-cephalosporin (ESC)-resistant infections due to blaTEMor blaSHV. DNA analysis assessed β-lactamase (bla) genes, multilocus sequence types, and E. coli phylogenetic grouping. Controls had ESC-susceptible Ent infections, matched 3:1 to cases by age, source, and hospital. Clinical-epidemiologic infection predictors were assessed. Results: Of 356 ESC-R-Ent isolates from children (median 4.3 years), 38 (10.7%) were positive solely for blaTEM-ESBL(26%) or blaSHV-ESBLgenes (74%). Predominant organisms were Klebsiella (34.2%) and E. coli (31.6%); 67% of E. coli were phylogroup B2. Multilocus sequence types revealed multiple strains, 58% resistant to ≥3 antibiotic classes. On multivariable analysis, children with TEM-SHV-Ent infections more often had recent inpatient care (OR, 8.2), yet were diagnosed mostly as outpatients (OR, 25.6) and less in Neonatal Intensive Care Units (OR, 0.036) than controls. TEM-SHV-Ent patients had more gastrointestinal (OR, 23.7) and renal comorbidities (OR, 4.2). Differences in demographics, antibiotic exposure, and foreign bodies were not found. Conclusion: TEM-SHV-Ent are commonly linked to inpatient exposures in children with chronic conditions but most often present in outpatient settings. Clinicians should be aware of the potential increased risk for TEM-SHV-Ent infections in outpatients with gastrointestinal and renal comorbidities and histories of prolonged hospital stays.

Original languageEnglish (US)
Pages (from-to)39-43
Number of pages5
JournalPediatric Infectious Disease Journal
Volume40
Issue number1
DOIs
StatePublished - Jan 1 2021

Funding

Supported by National Institutes of Health—National Institute of Allergy and Infectious Diseases grant K08AI112506 (L.K.L.) and grants R01AI072219, R01AI063517, and R01AI100560 (R.A.B.). This work was also supported by the Department of Veterans Affairs Research and Development under award number I01BX001974, VISN 10 Geriatrics Research, Education, and Clinical Center (R.A.B.). We gratefully acknowledge the contribution of the late Dr. Paul Schreckenberger to this work. We thank the microbiology laboratories of the participating institutions for providing isolates for this study. We thank Kendrick Reme of the Logan Laboratory and Diane Springer, Joyce Houlihan, Kathleen McKinley, Violeta Rekasiu, Cindy Bethel, and Donna Carter of participating institutions for collection, shipping, and cultivation of organisms. We thank the team of curators of the Institut Pasteur MLST and whole-genome MLST databases for curating the data and making them publicly available at http://bigsdb.web.pasteur.fr/. This publication also made use of the Enterobacter cloacae MLST website (https:// pubmlst.org/ecloacae/) sited at the University of Oxford. The development of the pubmlst.org site has been funded by the Wellcome Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs.

Keywords

  • Enterobacterales infections
  • Gram-negative bacteria
  • children
  • drug resistance
  • epidemiology

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pediatrics, Perinatology, and Child Health

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