Toward antibiotic stewardship: Route of antibiotic administration impacts the microbiota and resistance gene diversity in swine feces

Authors: RICKER, NICOLE - Orise Fellow; Trachsel, Julian; COLGAN, PHILLIP - Iowa State University; Jones, Jennifer; CHOI, JIN - Iowa State University; LEE, JAEJIN - Iowa State University; COETZEE, JOHANN - Kansas State University; HOWE, ADINA - Iowa State University; Brockmeier, Susan; Loving, Crystal; Allen, Heather

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/17/2020
Publication Date: 5/19/2020
Citation: Ricker, N., Trachsel, J.M., Colgan, P., Jones, J., Choi, J., Lee, J., Coetzee, J., Howe, A., Brockmeier, S., Loving, C.L., Allen, H.K. 2020. Toward antibiotic stewardship: Route of antibiotic administration impacts the microbiota and resistance gene diversity in swine feces. Frontiers in Veterinary Science. 7:255. https://doi.org/10.3389/fvets.2020.00255.
DOI: https://doi.org/10.3389/fvets.2020.00255

Interpretive Summary: Antibiotic resistance is a global concern, and calls for improved antibiotic stewardship in human and animal medicine. Antibiotics remain an important tool for limiting disease in swine, and while commonly delivered via oral administration in feed or water, injectable formulations are available. While the in-feed route is easier than injected to administer at the herd level, in-feed may have more impact on intestinal bacterial populations, including those harboring antibiotic resistance genes. A study was performed to compare impact of therapeutic dose of oxytetracycline in-feed versus injected on levels of oxytetracylcine in blood and feces, intestinal bacteria, and antibiotic resistance gene abundance. The in-feed route of antibiotic administration caused a greater shift to gut bacterial community and the abundance of some antibiotic resistance genes when compared to intramuscular injection. Specifically, two genes that confer resistance to tetracycline-family antibiotics increased in abundance in the guts of pigs fed oxytetracycline compared to bacteria in intestine of pigs in non-medicated and injected groups. In addition, increased abundance of a gene that confers resistance to an antibiotic not administered (aminoglycoside-family antibiotics) was detected in the in-feed group. Concentration of oxytetracycline was greatest in feces of pigs given in-feed oxytetracycline, compared to injected group, whereas levels were highest in plasma of the injected group. This research shows that in-feed antibiotic administration has a greater impact on the gut microbiota than intramuscular administration, and provides evidence that parenteral administration may mitigate the selection pressure for antibiotic resistance and while still providing a method to limit disease in swine.

Technical Abstract: Antibiotic-resistant bacterial infections are a global health crisis, which has resulted in calls for improved antibiotic stewardship in both human medicine and animal agriculture. Antibiotics are administered to food-producing animals to treat and prevent disease, and antibiotics are commonly administered via the oral route due to ease of delivery at the herd level. Altering antibiotic administration route may limit impact on intestinal microbiota, and reduce pressure on antimicrobial resistance gene (ARG) abundance and mobility. Thus, a study was performed in pigs to evaluate route of therapeutic oxytetracycline administration, an antibiotic commonly used in the U.S. swine industry, on intestinal microbial diversity and ARG abundance. Given that oral antibiotics would be in direct contact with intestinal bacteria, we hypothesized that oral administration would cause a major shift in intestinal bacterial community structure when compared to injected antibiotic. We further postulated that the impact would extend to the diversity and abundance of ARG in swine feces. Oxytet concentrations in the plasma revealed that injected antibiotics resulted in a spike one day after administration, which decreased over time, though plasma oxytet was still detected 14 days after administration. Conversely, in-feed oxytet delivery resulted in lower but less variable oxytet levels in circulation. Fecal bacterial community diversity was impacted by treatment, and the in-feed treatment group was significantly different from both the injected and non-medicated groups. Fecal ARG abundance was increased with in-feed administration over injected, with genes for tetracycline and aminoglycoside resistance enriched in the in-feed group. While injected oxytet resulted in a higher concentration of antibiotic in plasma, the disturbance on the gut microbial community and ARG abundance was limited. Findings are informative for disease management in food animals, but also manure management and antibiotic therapy in human medicine for integrated improved antibiotic stewardship.