A dairy farm can make a concerted effort to limit antimicrobial use and still have resistance genes represented in its cattle microbiome. Tetracycline resistance is one example. Recent research from the University of Wisconsin found these genes remained common on farms reporting relatively low antimicrobial use, raising questions about how resistance persists and what veterinarians should consider when making treatment decisions.
Across eight commercial Wisconsin dairy farms, tetracycline resistance genes were prevalent regardless of whether farms were classified as low or high antimicrobial users. The findings also revealed substantial differences among cattle groups, suggesting that a farm’s overall antimicrobial-use numbers may miss important details about resistance within the herd.
Resistance Can Persist Beyond Current Antimicrobial Use
The study included four low-use and four high-use dairy farms. Average antimicrobial use was 9.76 defined daily doses per 1,000 herd-days on low-use farms, compared with 28.6 on high-use farms. Fecal samples were collected from calves, healthy lactating cows, sick cows and cull cows during four sampling visits in 2020. Metagenomic sequencing was used to characterize antimicrobial resistance genes in the samples.
Tetracycline and beta-lactam resistance genes were among the most abundant classes across both farm groups. Despite the substantial difference in overall antimicrobial use, the composition of tetracycline resistance genes did not differ significantly between low- and high-use farms. Other resistance classes, however, showed associations with antimicrobial use. Several clinically relevant beta-lactamase genes, including blaCMY and blaCTX, were less abundant on low-use farms.
The persistence of tetracycline resistance may reflect several factors beyond current treatment practices:
- Historical antimicrobial exposure: Resistance genes can remain in bacterial populations after the antimicrobial selection pressure that initially favored them has declined.
- Co-selection: Exposure to other antimicrobials or environmental compounds can favor bacteria carrying multiple resistance genes, including tetracycline resistance genes.
- Environmental reservoirs: Manure, soil and water can harbor bacteria and resistance genes, potentially allowing them to persist beyond the animals currently receiving treatment.
Previous research offers some context for these possibilities. A 2019 study detected tetracycline resistance genes in both conventional and raised-without-antibiotics beef and dairy production systems, including a dairy operation that had reportedly gone 14 years without antibiotic use. Other studies have documented the persistence of tetracycline resistance genes in soils amended with cattle feces, including after manure application or antimicrobial selection pressure ended.
These studies do not establish why tetracycline resistance remained common on the Wisconsin farms. They do, however, show that resistance genes can persist in production environments beyond the period of active antimicrobial use.
So why does tetracycline resistance persist when current antimicrobial use is relatively low? Available evidence points to several possible contributors as listed above, but as the researchers put it, “Some resistance classes are ubiquitous in dairy systems regardless of historical AMU.”
Calves Add Another Layer to the Resistance Picture
Cattle group was another important factor in the study. Calves had the greatest richness and diversity of antimicrobial resistance genes compared with healthy lactating cows, sick cows and cull cows.
Tetracycline resistance genes accounted for 48.8% of the relative abundance of resistance genes in calves, compared with 36.5% in adult cattle. Beta-lactam resistance genes showed the opposite pattern, representing 16.8% and 36.8%, respectively.
Differences in antimicrobial exposure may help explain some of this variation. Calves may receive systemic or oral treatments, while adult dairy cows commonly receive intramammary antimicrobials. These routes can result in different levels of antimicrobial exposure in the gastrointestinal tract. Early-life microbial exposures from dams and the farm environment may also influence the calf resistome. The study did not establish where the resistance genes originated or which exposures were responsible for the differences.
The results highlight why antimicrobial resistance should be considered across different cattle groups rather than treated as a single herd-level measure.
What Does This Mean for Tetracycline Use?
The findings do not suggest that tetracyclines should be avoided or that switching to another antimicrobial class will necessarily reduce resistance. Treatment decisions still need to be based on the disease being treated, the likely pathogen, available diagnostic information and the expected effectiveness of the drug.
Instead, the results reinforce the value of thoughtful antimicrobial selection. Veterinarians can consider whether treatment is indicated, whether the chosen drug is appropriate for the suspected pathogen, and whether the dose, duration and route of administration are appropriate. Susceptibility testing, when available and relevant, can also help guide drug selection.
The study did not compare treatment alternatives or evaluate whether changing antimicrobial protocols would reduce tetracycline resistance. Resistance genes detected in fecal samples also do not necessarily indicate that clinical pathogens are resistant or that treatment will fail. The findings are a reminder that current antimicrobial use is only one part of a more complex resistance picture.
The Herd Average Can Hide Important Differences
Together, antimicrobial use and cattle group accounted for approximately 86% of the variation in resistome patterns. By comparison, the broad low- or high-use farm classification alone explained about 8.6% of the variation in resistance-class composition.
That distinction is important for interpreting antimicrobial-use data. A herd-level total can provide a useful overview, but it may not reflect which animals are exposed, which drug classes are used or how resistance patterns differ across the operation.
“The signal is easiest to detect when the analysis aligns with how antimicrobial exposure and selection actually occur in practice,” the researchers noted.
When evaluating antimicrobial use and resistance on dairy farms, the findings point to several considerations:
- Which cattle groups are being treated: Calves had the greatest resistance gene richness and diversity in this study.
- Which antimicrobial classes are being used: Associations with resistance varied by drug class.
- How exposure occurs: Treatment route can influence antimicrobial exposure in the gastrointestinal tract.
- What the data measure: Resistance genes detected in fecal samples do not necessarily indicate clinical resistance or predict treatment failure.
Antimicrobial resistance on dairy farms develops within a complex microbial and environmental system. Tracking antimicrobial use remains important, but understanding which animals are exposed, which drug classes are involved and how resistance differs among cattle groups can provide a more complete picture than herd-level totals alone.
