Dataset Information

Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse.

ABSTRACT: Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence in their enteric bacteria, including potential pathogens such as Escherichia coli. These bacteria can contaminate animal products at slaughterhouses and cause food-borne illness, which can be difficult to treat if it is due to antimicrobial resistant bacteria. One potential intervention to reduce the dissemination of resistant bacteria from feedlot to consumer is to impose a withdrawal period after antimicrobial use, similar to the current withdrawal period designed to prevent drug residues in edible animal meat. We investigated tetracycline resistance in generic E. coli in the bovine large intestine during and after antimicrobial treatment by building a mathematical model of oral chlortetracycline pharmacokinetics-pharmacodynamics and E. coli population dynamics. We tracked three E. coli subpopulations (susceptible, intermediate, and resistant) during and after treatment with each of three United States chlortetracycline indications (liver abscess reduction, disease control, disease treatment). We compared the proportion of resistant E. coli before antimicrobial use to that at several time points after treatment and found a greater proportion of resistant enteric E. coli after the current withdrawal periods than prior to treatment. In order for the proportion of resistant E. coli in the median beef steer to return to the pre-treatment level, withdrawal periods of 15 days after liver abscess reduction dosing (70 mg daily), 31 days after disease control dosing (350 mg daily), and 36 days after disease treatment dosing (22 mg/kg bodyweight for 5 days) are required in this model. These antimicrobial resistance withdrawal periods would be substantially longer than the current U.S. withdrawals of 0-2 days or Canadian withdrawals of 5-10 days. One published field study found similar time periods necessary to reduce the proportion of resistant E. coli following chlortetracycline disease treatment to those suggested by this model, but additional carefully designed field studies are necessary to confirm the model results. This model is limited to biological processes within the cattle and does not include resistance selection in the feedlot environment or co-selection of chlortetracycline resistance following other antimicrobial use.

SUBMITTER: Cazer CL

PROVIDER: S-EPMC5627025 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse.

Cazer Casey L CL Ducrot Lucas L Volkova Victoriya V VV Gröhn Yrjö T YT

Frontiers in microbiology 20170920

Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence in their enteric bacteria, including potential pathogens such as <i>Escherichia coli</i>. These bacteria can contaminate animal products at slaughterhouses and cause food-borne illness, which can be difficult to treat if it is due to antimicrobial resistant bacteria. One potential intervention to reduce the dissemination of resistant bacteria from feedlot to consumer is to impose a withdrawal period after antimicro ...[more]

PMID: 29033901

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Project description:Treatment of food-producing animals with antimicrobial drugs (AMD) is controversial because of concerns regarding promotion of antimicrobial resistance (AMR). To investigate this concern, resistance genes in metagenomic bovine fecal samples during a clinical trial were analyzed to assess the impacts of treatment on beef feedlot cattle resistomes. Four groups of cattle were exposed, using a 2-by-2 factorial design, to different regimens of antimicrobial treatment. Injections of ceftiofur crystalline-free acid (a third-generation cephalosporin) were used to treat all cattle in treatment pens or only a single animal, and either chlortetracycline was included in the feed of all cattle in a pen or the feed was untreated. On days 0 and 26, respectively, pre- and posttrial fecal samples were collected, and resistance genes were characterized using shotgun metagenomics. Treatment with ceftiofur was not associated with changes to β-lactam resistance genes. However, cattle fed chlortetracycline had a significant increase in relative abundance of tetracycline resistance genes. There was also an increase of an AMR class not administered during the study, which is a possible indicator of coselection of resistance genes. Samples analyzed in this study had previously been evaluated by culture characterization (Escherichia coli and Salmonella) and quantitative PCR (qPCR) of metagenomic fecal DNA, which allowed comparison of results with this study. In the majority of samples, genes that were selectively enriched through culture and qPCR were not identified through shotgun metagenomic sequencing in this study, suggesting that changes previously documented did not reflect changes affecting the majority of bacterial genetic elements found in the predominant fecal resistome.IMPORTANCE Despite significant concerns about public health implications of AMR in relation to use of AMD in food animals, there are many unknowns about the long- and short-term impact of common uses of AMD for treatment, control, and prevention of disease. Additionally, questions commonly arise regarding how to best measure and quantify AMR genes in relation to public health risks and how to determine which genes are most important. These data provide an introductory view of the utility of using shotgun metagenomic sequencing data as an outcome for clinical trials evaluating the impact of using AMD in food animals.

Dataset Information

Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse.

Publications

Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse.

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