Abstract
Antimicrobial resistance represents a major global threat to modern medicine. In vitro studies have shown that very low concentrations of drugs, as frequently identified in the environment, and in foods and water for human and animal consumption, can select for resistant bacteria. However, limited information is currently available on the in vivo impact of ingested drug residues. The objective of our study was to evaluate the effect of feeding preweaned calves milk containing antimicrobial drug residues (below the minimum inhibitory concentration), similar to concentrations detected in milk commonly fed to dairy calves, on selection of resistant fecal E. coli in calves from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR), and 15 calves were fed raw milk with drug residues (DR) by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 µg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth prior to the first feeding in the trial (pre-treatment) until 6 weeks of age. A significantly greater proportion of E. coli resistant to ampicillin, cefoxitin, ceftiofur, streptomycin and tetracycline was observed in DR calves when compared to NR calves. Additionally, isolates from DR calves had a significant decrease in susceptibility to ceftriaxone and ceftiofur when compared to isolates from NR calves. A greater proportion of E. coli isolates from calves in the DR group were resistant to 3 or more antimicrobial drugs when compared to calves in the ND group. These findings highlight the role that low concentrations of antimicrobial drugs have on the evolution and selection of resistance to multiple antimicrobial drugs in vivo.
Highlights
The rapid development of antimicrobial resistance in the past few decades is considered one of the greatest global threats to modern medicine [1, 2]
Most antimicrobial drugs used to treat cows result in the milk from these animals being withheld from sale because of the presence of drug residues above the tolerance concentration established by the U.S Food and Drug Administration (FDA)
Our understanding of the impacts of low concentrations of drugs on antimicrobial resistance is still limited, in vitro studies have indicated that selection and maintenance of resistant bacteria can occur [32]
Summary
The rapid development of antimicrobial resistance in the past few decades is considered one of the greatest global threats to modern medicine [1, 2]. In the dairy industry diseases have a great impact, resulting in treatment expenses and production losses such as lower milk yield and withholding of milk due to presence of drug residues [5]. Most antimicrobial drugs used to treat cows result in the milk from these animals being withheld from sale (waste milk) because of the presence of drug residues above the tolerance concentration established by the U.S Food and Drug Administration (FDA). To decrease production losses due to waste milk, 33% of dairy farms in the United States feed preweaned calves waste milk [7]. Feeding pasteurized waste milk instead of milk replacer to preweaned calves has been shown to result in an estimated saving of $0.69 per calf per day [8]
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