Korving, L. | bioRxiv Science

bioRxiv2024

Flumequine, a fluoroquinolone in disguise

Fluoroquinolone resistance in E. coli isolates from livestock in Europe remains high even though the EMA restricted fluoroquinolone use in animals. However, flumequine, a quinolone similar to fluoroquinolones, is still used in livestock in the Netherland, Belgium, Greece or France. Therefore, we investigated whether flumequine selects for the same resistance mechanisms in E. coli. To accomplish this, we investigated and enumerated resistant and non-resistant E. coli isolates obtained from caecal fermentation assays and from broilers exposed to different concentrations of flumequine and enrofloxacin. Flumequine usage leads to approximately 3-fold increase of resistant E. coli in the caecal fermentation, comparable with enrofloxacin. After in vitro exposure to flumequine and enrofloxacin we detected the same SNPs (S83L, D87G) in gyrA. Furthermore, the same resistance-causing SNPs were found in phenotypic resistant E. coli isolates from broilers treated with enrofloxacin and flumequine. Flumequine induces similar resistance mechanisms as enrofloxacin and restriction for use should be the same.

microbiology↗

bioRxiv2023

Defining minimal selective concentrations of amoxicillin, doxycycline and enrofloxacin in broiler-derived cecal fermentations by phenotype, microbiome and resistome

Antimicrobial resistance (AMR) is an emerging worldwide problem. Exposure to antimicrobials selects for resistant bacteria which are a health threat for humans and animals. The concentration at which selection for resistant bacteria occurs is often lower than the minimum inhibitory concentration (MIC) and also differs between environments. Defining this minimal selective concentration (MSC) under natural conditions is essential to understand the selective window for resistant bacteria which are exposed to residual antimicrobials in humans, animals and the environment. In this study we estimated the MSCs of three antimicrobial compounds, amoxicillin, doxycycline and enrofloxacin in a complex microbial community by conducting fermentation assays with cecal material derived from broilers. We examined the phenotypic resistance of Escherichia coli, resistome and microbiome after 6 and 30 hours of fermenting in the presence of antimicrobials of interest. The concentrations are 10 to 100 times lower than the epidemiological cut-off values in E. coli for the respective antimicrobials as determined by EUCAST (https://mic.eucast.org/). In contrast to the amoxicillin and doxycycline exposure we could not determine any molecular resistance mechanism in the resistome analysis for the enrofloxacin exposure, likely because they are the result of point mutations. Our findings show at which concentrations there still is selection for AMR bacteria. This knowledge can be used to manage the risk of the emergence of AMR bacteria. ImportanceAntimicrobial resistance is an emerging threat to the health of humans and animals; it might affect economic prosperity in the future. The rise of antimicrobial resistant bacteria is a consequence of the use of antimicrobial compounds in humans and animals which selects for resistant bacteria. It is critical to understand the relation between the concentrations of antimicrobial compounds and their selection for antimicrobial resistant bacteria. In our study we are providing the minimal selective concentrations for amoxicillin, doxycycline and enrofloxacin by using cecal fermentations assays.

microbiology↗