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Simple Summary Antibiotics perturb the gastrointestinal microbiota by killing bacteria beneficial for animal health and favoring the emergence of potential pathogens. Furthermore, antibiotics favor the emergence of resistant bacteria. Current knowledge on animals’ intestinal microbiota and effects of antibiotics is blurred by the various posology, administration routes, and implemented methodologies for its analysis. We summarized 71 studies analyzing the administration of antibiotics by different routes, conducted on the main food-producing and companion animals, highlighting differences in the methodology applied for the intestinal microbiota and antibiotic resistance analysis. Overall, therapeutic dosage decreased bacterial species diversity and richness in the microbiota and selected antibiotic resistance genes. For non-therapeutic dosage, information on the selection of antibiotic resistance was scarce and the effect on the intestinal microbiota scattered. Understanding the gut microbiota composition and function in animals could open up strategies for its modulation to improve animal health and performance, and to minimize the negative impact of antibiotics. Abstract Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of ARGs. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals’ health status, with positive consequences on global health.

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Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended- spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other—mostly older—antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.

Resistance to carbapenems in animals in the absence of use. Carbapenems, a class among beta-lactams are antibiotics of crucial importance in human medicine. Even though carbapenems are not authorized in veterinary medicine, various bacteria harbouring resistance to carbapenems have been reported in the animal sector. Here, based on recent examples, we provide an update on the epidemiological situation of carbapenem resistance in domestic animals in France. Notably, the case of Pseudomonas aeruginosa in the context of external otitis in dogs highlights to what extent resistance to carbapenems may have likely been selected by the use of fluoroquinolones and/ or aminoglycosides. At the end, these data stress again the importance of a rational use of antibiotics at any time in veterinary medicine., Les carbapénèmes, classe d’antibiotiques naturels ou semi-synthétiques de la famille des bêta-lactamines sont des antibiotiques de première importance en médecine humaine. Même si l’usage des carbapénèmes est interdit en médecine vétérinaire (antibiotiques critiques), des souches bactériennes résistantes à cette classe d’antibiotiques sont décrites dans le secteur animal. À partir d’exemple récents, cette communication a pour objectif de faire un point sur la situation chez l’animal domestique en France. En particulier, l’exemple de Pseudomonas aeruginosa dans des infections cutanées chez le chien illustre comment la résistance aux carbapénèmes est très probablement sélectionnée par l’usage des fluoroquinolones et/ ou des aminosides (mécanismes d’efflux). Au final, ces éléments constituent une occasion supplémentaire de rappeler à la profession vétérinaire, l’importance de l’usage raisonné des antibiotiques en toutes circonstances., Haenni Marisa, Lupo Agnese, Madec Jean-Yves. Résistance aux carbapénèmes chez les animaux en l’absence d’usage. In: Bulletin de l'Académie Vétérinaire de France tome 171 n°1, 2018. pp. 4-8.

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