Abstract
A pair-matched longitudinal study conducted on three dairy farms in the U.S. High-Plains explored the temporal effects of two-dose ceftiofur crystalline-free acid (CCFA) treatment for metritis on third-generation cephalosporin (3GC) resistance among enteric E. coli in Holstein-Friesian cows. The current 13-day slaughter withholding period does not account for rising populations of third-generation cephalosporin (3GC) resistant bacteria in feces of animals following CCFA treatment. A total of 124 matched-pairs of cows were enrolled in the study. Cows diagnosed with postpartum metritis received the product twice at the labeled dose of 6.6 mg/kg subcutaneously at the base of alternating ears. Untreated cows–absent clinical metritis–were matched on lactation number and calving date. Feces were collected per rectum on days 0 (baseline), 6, 16, 28, and 56. Environmental samples, from watering troughs as well as surface manure from fresh-cow, hospital, maternity, and milking pens, and from the compost pile were collected prior to the animal sample collection period. Historical data on metritis rates and CCFA use were compiled from herd records. On day 0, cows exhibited an overall mean difference of over 4 log10 colony forming units (CFU) comparing 3GC resistant E. coli to the general E. coli population. At the first eligible slaughter date, the difference declined to 3.31 log10 CFU among cows in the CCFA group (P<0.01 compared to control cows). Such differences were no longer observed between the treated and control groups by day 28. Results suggest a 13-day withholding period following the final treatment is insufficient to allow levels of 3GC resistant E. coli to return to baseline. This effect varied by farm and was dependent upon the starting level of resistance. A farm-specific extended slaughter-withholding period could reduce the microbial risk to food products at slaughter.
Highlights
Over the past five decades, antimicrobial resistance (AMR) among bacteria of clinical importance has continued to expand its threat to public health, drawing the attention of national and international agencies, researchers, and industry [1]
Total E. coli colony forming units (CFU) counts were similar across all three dairy farms; Dairy Farm 3 had mean quantifiable levels of 3GC resistant E. coli approximately 1.5 log10 CFU greater than the other two farms (Dairy Farm 1 95% CI: 0.575– 3.116; Dairy Farm 2 95% CI: 0.286–2.939; Dairy Farm 3 95% CI: 1.765–4.575; Table 1)
The data show that a 13-day withholding period from the final administration of a two-dose treatment of ceftiofur crystalline-free acid (CCFA) for metritis may be insufficient to ensure that 3GC resistant E. coli populations return to baseline levels in all treated cattle and mitigate the risk of these organisms “escaping from the farm” as illustrated in the risk assessment of Hurd [28, 29]
Summary
Over the past five decades, antimicrobial resistance (AMR) among bacteria of clinical importance has continued to expand its threat to public health, drawing the attention of national and international agencies, researchers, and industry [1]. Metritis is a common postpartum disease in dairy cows, clinically expressed as fever above 39.5 ̊C, with a thickened uterine wall, and emitting a malodorous reddish-brown discharge [3]. These symptoms typically occur within 21 days after calving [3]. Prior to April 2012, a single-dose treatment with ceftiofur crystalline-free acid (CCFA) was on-label for treatment of metritis; subsequently, a two-dose treatment is required to remain on-label Antibiotics, such as CCFA, are frequently used to treat metritis in dairy cows; penicillin, ampicillin, and oxytetracycline can be prescribed in dairy production settings [8,9,10,11]. This has since changed, as the U.S Food and Drug Administration (FDA) banned most extra-label uses of cephalosporins in food animals in 2012 [15]
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