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      Antimicrobial resistance of Clostridioides difficile in veterinary medicine around the world: A scoping review of minimum inhibitory concentrations

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          Abstract

          Objective

          To provide a comprehensive characterization of Clostridioides difficile antimicrobial resistance (AMR) data in veterinary medicine based on the minimum inhibitory concentrations (MICs) of all antimicrobial agents tested in relation to the techniques used.

          Methods

          A systematic scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR) and its associated checklist. The objective was to provide a synthesis of the evidence in a summarized and analyzed format.

          To this end, three scientific databases were consulted: Scopus, PubMed, and Web of Science, up until December 2021. Subsequently, all identified literature was subjected to screening and classification in accordance with the established study criteria, with the objective of subsequent evaluation.

          Study selection and data extraction

          A comprehensive analysis was conducted on studies regarding Clostridioides difficile antimicrobial resistance (AMR) in veterinary medicine across various animal species and related sources. The analysis included studies that presented data on antimicrobial susceptibility testing using the E-test, agar dilution, or broth microdilution techniques. The extracted data included minimum inhibitory concentration (MIC) values and a comprehensive characterization analysis.

          Results

          A total of 1582 studies were identified in scientific databases, of which only 80 were subjected to analysis. The research on Clostridioides difficile antimicrobial resistance (AMR) in veterinary medicine is most prolific in Europe and North America. The majority of isolates originate from production animals (55%) and pets (15%), with pigs, horses, and cattle being the most commonly studied species. The tested agents' minimum inhibitory concentrations (MICs) and resulting putative antimicrobial resistance profiles exhibited considerable diversity across animal species and sources of isolation. Additionally, AMR characterization has been conducted at the gene and genomic level in animal strains. The E-test was the most frequently utilized method for antimicrobial susceptibility testing (AST). Furthermore, the breakpoints for interpreting the MICs were found to be highly heterogeneous and frequently observed regardless of the geographical origin of the publication.

          Conclusions

          Antimicrobial susceptibility testing techniques and results were found to be diverse and heterogeneous. There is no evidence of an exclusive antimicrobial resistance pattern in any animal species. Despite the phenotypic and genomic data collected over the years, further interdisciplinary studies are necessary. Our findings underscore the necessity for international collaboration to establish uniform standards for C. difficile antimicrobial susceptibility testing (AST) methods and reporting. Such collaboration would facilitate a “One Health” approach to surveillance and control, which is of paramount importance.

          Graphical abstract

          Highlights

          • AMR data from 80 studies and >4600 isolates worldwide was assessed.

          • AST methodologies and interpretative criteria are heterogeneous across literature.

          • Production animals and pets' reports constitutes most of AMR data.

          • AMR profiles are highly diverse across animal species.

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          Most cited references100

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          Clostridium difficile infection

          Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.
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            AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence

            Antimicrobial resistance (AMR) is a significant public health threat. With the rise of affordable whole genome sequencing, in silico approaches to assessing AMR gene content can be used to detect known resistance mechanisms and potentially identify novel mechanisms. To enable accurate assessment of AMR gene content, as part of a multi-agency collaboration, NCBI developed a comprehensive AMR gene database, the Bacterial Antimicrobial Resistance Reference Gene Database and the AMR gene detection tool AMRFinder. Here, we describe the expansion of the Reference Gene Database, now called the Reference Gene Catalog, to include putative acid, biocide, metal, stress resistance genes, in addition to virulence genes and species-specific point mutations. Genes and point mutations are classified by broad functions, as well as more detailed functions. As we have expanded both the functional repertoire of identified genes and functionality, NCBI released a new version of AMRFinder, known as AMRFinderPlus. This new tool allows users the option to utilize only the core set of AMR elements, or include stress response and virulence genes, too. AMRFinderPlus can detect acquired genes and point mutations in both protein and nucleotide sequence. In addition, the evidence used to identify the gene has been expanded to include whether nucleotide or protein sequence was used, its location in the contig, and presence of an internal stop codon. These database improvements and functional expansions will enable increased precision in identifying AMR genes, linking AMR genotypes and phenotypes, and determining possible relationships between AMR, virulence, and stress response.
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              Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O'Toole 1935) Prévot 1938.

              The recent proposal by Lawson and Rainey (2015) to restrict the genus Clostridium to Clostridium butyricum and related species has ramifications for the members of the genera that fall outside this clade that should not be considered as Clostridium sensu stricto. One such organism of profound medical importance is Clostridioides difficile that is a major cause of hospital-acquired diarrhea and mortality in individuals. Based on 16S rRNA gene sequence analysis, the closest relative of Clostridium difficile is Clostridium mangenotii with a 94.7% similarity value and both are located within the family Peptostreptococcaceae that is phylogenetically far removed from C. butyricum and other members of Clostridium sensu stricto. Clostridium difficile is Clostridium mangenotii each produce abundant H2 gas when grown in PYG broth and also produce a range of straight and branched chain saturated and unsaturated fatty acids with C16:0 as a major product. The cell wall peptidoglycan contains meso-DAP as the diagnostic diamino acid. Based on phenotypic, chemotaxonomic and phylogenetic analyses, novel genus Clostridioides gen. nov. is proposed for Clostridium difficile as Clostridioides difficile gen. nov. comb. nov. and that Clostridium mangenotii be transferred to this genus as Clostridioides mangenotii comb. nov. The type species of Clostridioides is Clostridioides difficile.
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                Author and article information

                Contributors
                Journal
                One Health
                One Health
                One Health
                Elsevier
                2352-7714
                20 July 2024
                December 2024
                20 July 2024
                : 19
                : 100860
                Affiliations
                [a ]Grupo de Investigación en Enfermedades de Etiología Microbiana (GIEEM) & Observatorio Universitario de Genómica y Resistencia Antimicrobiana (OUGRAM), Instituto de Investigaciones en Microbiología (IIM), Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras, Honduras
                [b ]Institute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, Jena, Germany
                [c ]Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany
                [d ]Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany
                Author notes
                Article
                S2352-7714(24)00186-1 100860
                10.1016/j.onehlt.2024.100860
                11327573
                a4d8ba97-e0e7-4f68-9944-685b2f8f21ab
                © 2024 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 4 April 2024
                : 16 July 2024
                : 16 July 2024
                Categories
                Review Paper

                clostridium difficile,clostridioides,antimicrobial resistance,veterinary,animal,antimicrobial susceptibility testing,one health

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