A study to examine the relationship between metritis severity and depletion of oxytetracycline in plasma and milk after intrauterine infusion

Abstract

Metritis is a frequent problem in postpartum dairy cows. Intrauterine therapy with the antimicrobial oxytetracycline (OTC) is often used, although this therapy has not been shown to be superior to systemic therapy. The objectives of this study were to (1) determine the plasma and milk concentrations of OTC following intrauterine infusion in postpartum dairy cows with varying degrees of metritis severity; (2) determine the depletion time of OTC in an attempt to provide veterinarians withdrawal guidelines, should they use this therapy; and (3) correlate metritis severity scores with OTC concentrations in plasma and milk. Our hypothesis was that cows with more severe metritis would have higher OTC concentrations in milk following intrauterine therapy. Thirty-two cows were selected to participate in the study after farm personnel had determined that they had metritis based on evaluation of vaginal discharge between 4 and 14 DIM, in accordance with the farm's treatment protocols. Metritis scores (1-4) were assigned based on a published scheme: 1 represented yellow-to-orange thick discharge or translucent mucus with no fetid smell; 2 represented blood-tinged vaginal mucus, slightly watery, with little or no fetid smell; 3 represented red to red/brown watery discharge with moderate fetid smell; and 4 represented red to red/brown watery discharge containing pieces of placenta and an intense fetid smell. Trial cows received a single treatment of 4g of OTC (approximately 6.7mg/kg) via intrauterine infusion. Blood samples were collected over 96h, and milk samples were collected before intrauterine therapy and 3 times a day for 4 d following infusion. Following treatment, OTC rapidly diffused to plasma and subsequently to milk. Maximum OTC concentrations in plasma and milk occurred within the first 24h following intrauterine infusion, and 25 of the 32 cows had detectable OTC concentrations in milk at 4 d after intrauterine infusion. Cows with clinical metritis (metritis severity scores of 3 or 4) at the initiation of treatment were significantly and positively correlated with higher milk OTC concentrations at the second [time (T)9 h; r=0.43], fourth (T25 h; r=0.42), and fifth milking following treatment (T33 h; r=0.38) compared with cows with normal vaginal discharge. We also observed a positive correlation between initial metritis score and milk maximum concentration (r=0.36) and milk area under the concentration curve (r=0.36). Given that intrauterine administration of OTC is an extra-label therapy, dairy producers should consult with their veterinarian to ensure that milk is being tested at or below the established tolerance for OTC. This will ensure that violative drug residues do not enter the human food supply.

Evaluation of tetracycline in milk following extra-label administration of topical tetracycline for digital dermatitis in dairy cattle

“…In the present study, tetracycline was present in 22% of all milk samples, but only 1% of all milk samples had concentrations higher than the Canadian MRL of 100 ng/mL. Tetracycline-class drug residues higher than 100 ng/mL have been reported in milk samples after intravenous, intramuscular, subcutaneous, and intrauterine administration (Anderson et al, 1995;Gorden et al, 2016). A study by Rodrigues et al (2010) on 12 cows reported mean milk tetracycline concentrations from 0.1 to 6.2 ng/mL at 8 to 120 h following DD treatment with tetracycline.…”

“…Reporting tetracycline concentrations measured in the blood was of notable interest. It is anticipated that, after absorption following extravascular, oral, uterine, or intramammary routes of administration, tetracycline will distribute widely and quickly in the body, reaching low concentrations in plasma (Rodrigues et al, 2010;Gorden et al, 2016). However, we were not able to find relevant information regarding the absorption, distribution, and excretion of antibiotics when administered topically for lameness therapy in dairy cattle (Fajt and Apley, 2001).…”

“…When compared with our LC-MS/MS results, the sensitivity of the Charm ROSA TET test for tetracycline concentrations between 10 and 30 ng/ mL was low (50-70%); however, at tetracycline concentrations above 100 ng/mL, sensitivity was of 100%. Comparison of test characteristics to those obtained in other studies is challenging due to use of differing screening tests [e.g., Charm II Test for tetracycline (Anderson et al, 1995;Gorden et al, 2016), or Charm II 6700 system (Al-Mazeedi et al, 2010)]. In addition, comparison is difficult because not all studies evaluated similar diagnostic test characteristics (Anderson et al, 1995) or only compared Charm-positive or suspected positive samples to a gold standard (LC-MS/MS; Al-Mazeedi et al, 2010).…”

“…Overall, when using a high dose of tetracycline (50 g/cow), it is likely that tetracycline would be below 100 ng/mL with a minimum withdrawal interval of 70 h for milk discard from an individual treated cow. If 1 cow in a 10-cow herd was treated using a maximum of 10 g of tetracycline per cow, it is likely that tetracycline concentrations at bulk tank level would not exceed 300 ng/mL at a milk withdrawal interval of 0 h. In agreement with Gorden et al (2016), withdrawal interval estimates should be accompanied with residue-screening tests on all treated animals to ensure food safety.…”

“…In the United States, there have been reports of quantifiable levels of tetracycline in milk samples purchased from supermarkets (Fritz and Zuo, 2007) and quantifiable oxytetracycline concentrations in milk following intrauterine therapy (Gorden et al, 2016). Studies from the Middle East have reported the presence of tetracycline higher than the allowable maximum levels (100 ng/mL) in pasteurized milk samples collected from markets (Al-Mazeedi et al, 2010;Mesgari Abbasi et al, 2011).…”