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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.
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.
Abstract:
Urinary tract infections (UTIs) are common in children and are predominantly caused by uropathogenic Escherichia coli (UPEC). An increasing proportion of these strains produce extended-spectrum β-lactamases (ESBLs), which render β-lactam antibiotics ineffective. Interestingly, some patients with ESBL-producing UTIs improve clinically following treatment with antibiotics like cephalexin, despite demonstrated in vitro resistance. Working alongside and at times synergistically with antibiotics, host immune factors, such as the antimicrobial peptide cathelicidin (LL-37), contribute to bacterial clearance through direct killing and inhibition of biofilm formation. In this review, we summarize the current understanding of pediatric ESBL-producing UPEC infections and present selected in vitro and in vivo experimental data evaluating the combined effects of LL-37 and cephalexin on clinical isolates. Although no synergy was observed, ESBL-producing isolates demonstrated reduced bacterial burden in vivo compared to a non-ESBL UPEC strain. These findings suggest that host immune factors and environmental conditions may influence the fitness and virulence of drug-resistant UTI pathogens, warranting further investigation.
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