# Fluoroquinolone Resistance Patterns in Multidrug-Resistant Escherichia coli from the Gut Microbiota of Young Children

## TL;DR

This study shows that fluoroquinolone-resistant E. coli is increasing in young children's gut microbiota in Russia, posing a public health risk due to the spread of antibiotic resistance.

## Contribution

The study identifies specific genetic mutations and resistance patterns in fluoroquinolone-resistant E. coli from children, highlighting the role of the gut microbiota as a reservoir for multidrug-resistant clones.

## Key findings

- The frequency of multidrug-resistant E. coli in children's gut microbiota increased from 15.7% to 32.5% over a decade.
- Resistance to moxifloxacin (MFX) was highest at 80.9%, with distinct genetic pathways for resistance to different fluoroquinolones.
- ST131 and ST38 clones were predominant in multidrug-resistant E. coli isolates from children.

## Abstract

Background/Objectives: The high prevalence of fluoroquinolone-resistant E. coli in healthy children represents a significant public-health risk, facilitating the spread of antimicrobial resistance and increasing the potential for difficult-to-treat extraintestinal infections with severe clinical outcomes. This study aimed to investigate the prevalence of fluoroquinolone resistance in multidrug-resistant E. coli isolated from presumptively healthy children in St. Petersburg, Russia, with a particular focus on fluoroquinolone resistance determinants. Methods: Phenotypic AST was performed on 307 E. coli isolates from fecal pediatric samples, comprising 230 isolates from 2012 to 2013 and 77 isolates from 2021 to 2022. A subset (n = 47) of MDR isolates underwent whole-genome sequencing. Results: The frequency of MDR E. coli strains rose significantly from 15.7% to 32.5% over the study period. The most significant increases in resistance among E. coli strains were to third-generation cephalosporins (CTX, CTZ) and fluoroquinolones (CIP), rising fourfold over a decade. Based on phenotypic resistance profiles of MDR E. coli to quinolones, the highest resistance rates were observed for MFX (80.9%) followed by NAL (74.5%), LVX (44.7%) and CIP (40.4%). Genotypic analysis revealed distinct pathways: low-level NAL resistance required only an S83 mutation in gyrA, whereas low-level MFX resistance was predominantly conferred by a plasmid-borne qnr gene. In contrast, resistance to CIP and LVX involved at least three QRDR mutations: S83L and D87N/Y in gyrA, and S80I in parC. Notably, our study showed the predominance of the ST131 and ST38 clones in E. coli isolated from pediatric samples. Conclusions: Our findings suggest that the efficacy of moxifloxacin for empirical treatment of infections caused by MDR E. coli might be severely compromised. Overall, the current study highlights that the pediatric gut microbiota serves as a reservoir for resistant E. coli with the expansion of multidrug-resistant clones independently of direct antibiotic selection pressure.