A murine model to study the gut bacteria parameters during complex antibiotics like cefotaxime and ceftriaxone treatment

Background: The globally increasing resistance due to extended-spectrum beta-lactamase producing Enterobacteriaceae is a major concern. The objective of this work was to develop a murine model to study the gut bacteria parameters during complex antibiotics like cefotaxime and ceftriaxone treatment and to compare the fecal carriage of ESBL-producing Enterobacteriaceae. Methods: SWISS mice were treated either with ceftriaxone or with cefotaxime or with NaCl 0.9% as a con-trol group from day 1 to day 5. We performed a gavage at day 4 with a Klebsiella pneumonia CTX-M9. We collected stools and performed pharmacological measurements, cultures and 16S rRNA gene amplifica-tion and sequencing during the 12 days of the stool collection. Results: Mice treated with ceftriaxone were more colonized than mice treated with cefotaxime after gav-age (p-value = 0.008; Kruskal-Wallis test). Ceftriaxone and cefotaxime were both excreted in large quan-tity in gut lumen but they drove architecture of the gut microbiota in different trajectories. Highest levels of colonization were associated with particular microbiota composition using principal coordinate anal-ysis (PCoA) which were more often achieved in ceftriaxone-treated mice and which were preceded by highest fecal antibiotics concentrations in both cefotaxime or ceftriaxone groups. Using LEfSe, we found that twelve taxa were significantly different between cefotaxime and ceftriaxone-treated mice. Using SplinectomeR, we found that relative abundances of Klebsiella were significantly higher in CRO than in CTX-treated mice (p-value = 0.01). Conclusion: Ceftriaxone selects a particular microbial community and its substitution for cefotaxime could prevent the selection of extended-spectrum beta-lactamase producing Enterobacteriaceae. (C) 2021 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Bio-technology.