Comparative genomic analysis of ESBL-producing from faecal carriage and febrile urinary tract infection in children: a prospective multicentre study.

Background: The reliability of ESBL-producing (ESBL-Ec) faecal carriage monitoring to guide probabilistic treatment of febrile urinary tract infection (FUTI) in children remains unclear.

Objectives: To compare the genomic characteristics of ESBL-Ec isolates from faecal carriage and FUTI to assess their correlation and identify a FUTI-associated virulence profile.

Methods: We conducted a prospective multicentre hospital and ambulatory-based study. We analysed the genotypes and virulence factors of both faecal and FUTI ESBL-Ec by whole genome sequencing. Correlations were assessed by non-parametric Spearman coefficient and virulence factors were assessed by chi-squared tests with Bonferroni correction.

Results: We included 218 ESBL-Ec causing FUTI and 154 ESBL-Ec faecal carriage isolates. The most frequent ST was ST131 (44%) in both collections. We found high correlation between carriage and ESBL-Ec FUTI regarding genes/alleles (rho = 0.88, < 0.0001) and combinations of virulence genes, MLST and serotypes (rho = 0.90, < 0.0001, rho = 0.99, = 0.0003, rho = 0.97, = 0.005 respectively). Beside this strong correlation, we found five genes that were significantly associated with FUTI (, , , and ). The strongest association with FUTI was found with adhesin gene allele (54% in FUTI versus 16% in carriage) and for and gene alone or in combination (63% versus 24%).

Conclusions: The genomic profile of ESBL-Ec causing FUTI in children strongly correlates with faecal carriage isolates except for a few genes. The presence of and/or in a previously identified carriage strain could be used as a marker of uropathogenicity and may guide the empirical antimicrobial choice in subsequent FUTI.