Extended-Spectrum β-Lactamase-Producing Escherichia coli and Pediatric UTIs: A Review of the Literature and Selected

Vanessa Tamas1, Erlinda R Ulloa2,3, Monika Kumaraswamy4,5

  • 1Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.

PubMed

Insights

Pediatric urinary tract infections (UTIs) caused by drug-resistant E. coli may be impacted by host defenses. The antimicrobial peptide cathelicidin (LL-37) and cephalexin showed reduced bacterial burden in vivo, suggesting immune factors influence pathogen virulence.

Area of Science:

  • Pediatric infectious diseases
  • Microbiology
  • Immunology

Background:

  • Urinary tract infections (UTIs) are common in children, often caused by uropathogenic Escherichia coli (UPEC).
  • An increasing number of UPEC strains produce extended-spectrum β-lactamases (ESBLs), conferring resistance to crucial β-lactam antibiotics.
  • Clinical improvement in some patients with ESBL-producing UTIs treated with cephalexin, despite in vitro resistance, suggests alternative clearance mechanisms.

Purpose of the Study:

  • To review current knowledge on pediatric ESBL-producing UPEC infections.
  • To evaluate the combined effects of the antimicrobial peptide cathelicidin (LL-37) and cephalexin on clinical ESBL-producing UPEC isolates.
  • To investigate the role of host immune factors in combating drug-resistant UTI pathogens.

Main Methods:

  • Literature review of pediatric ESBL-producing UPEC infections.
  • In vitro and in vivo experimental evaluation of LL-37 and cephalexin combinations.
  • Assessment of bacterial burden in a relevant in vivo model.

Main Results:

  • No synergistic effect was observed between LL-37 and cephalexin in vitro or in vivo.
  • ESBL-producing UPEC isolates exhibited a reduced bacterial burden in vivo compared to non-ESBL UPEC strains.
  • These findings highlight the potential influence of host factors on pathogen fitness.

Conclusions:

  • Host immune factors, like LL-37, may play a significant role in controlling ESBL-producing UPEC infections, independent of antibiotic synergy.
  • Environmental conditions and host immunity can modulate the virulence and fitness of drug-resistant UTI pathogens.
  • Further research is warranted to elucidate the complex interplay between host defenses and antibiotic resistance in pediatric UTIs.

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