Objective—To determine whether a combination of vaccination and extended intramammary antimicrobial treatment would eliminate chronic intramammary Staphylococcus aureus infections in lactating dairy cows.
Design—Randomized controlled clinical trial.
Animals—50 dairy cows with chronic mastitis caused by S aureus.
Procedure—Cows were identified and paired within herd on the basis of days in milk, lactation number, milk production, and numbers of quarters infected. Treated cows (n = 20) received 3 doses of a polyvalent S aureus bacterin on days 1, 15, and 21 of the study along with intramammary administration of pirlimycin in all 4 quarters once daily for 5 treatments (days 16 to 20). Control cows (n = 23) received no treatment. Follow-up samples for bacteriologic culture were collected for at least 3 months after treatment to determine treatment success rates.
Results—Significantly more S aureus infections were eliminated from treated cows (8/20 [40%]), compared with control cows (2/23 [9%]). The proportion of infected quarters that yielded negative results throughout the follow-up period was also significantly higher in treated cows (13/28 [46%]) than in control cows (2/41 [5%]).
Conclusions and Clinical Relevance—Results indicate that a combination of vaccination and antimicrobial treatment can be successful in eliminating some cases of chronic intramammary S aureus infections in dairy cattle. However, it is important to consider extended treatment protocols carefully because many cows are likely to remain infected with S aureus despite treatment and vaccination.
Objective—To evaluate effects of 2 commercially available colostrum replacement products on serum IgG and total protein concentrations in dairy calves.
Design—Prospective clinical trial.
Animals—84 Holstein bull calves from a single dairy.
Procedures—Calves were randomly assigned to be given 4 quarts of colostrum (group 1; n = 21), 2 packages of a colostrum replacement product (product A; group 2; 21), 1 package of a different colostrum replacement product (product B; group 3; 21), or 2 packages of product B (group 4; 21). Treatments were given within 3 hours after birth, and blood samples were collected 24 hours later and submitted for determination of serum total protein and IgG concentrations.
Results—Group 1 calves had significantly higher serum total protein and IgG concentrations than did calves in the other 3 groups. However, the percentage of calves with adequate passive transfer (ie, serum IgG concentration > 1,000 mg/dL) was not significantly different among groups 1 (90%), 3 (81%), and 4 (95%). In contrast, only 10% of calves in group 2 had adequate passive transfer. It was predicted that calves fed product B that had serum total protein concentrations > 5.2 g/dL would have serum IgG concentrations > 1,000 mg/dL at least 90% of the time.
Conclusions and Clinical Relevance—Results indicated that product B could be considered as an alternative to colostrum in dairy calves, but product A failed to routinely provide adequate serum IgG concentrations when fed according to label directions.
Objective—To determine the effects of 3 commercially available, orally administered electrolyte solutions (OAEs) on abomasal luminal pH and emptying rate in dairy calves, compared with the effect of orally administered milk replacer.
Design—Randomized crossover study.
Animals—6 male dairy calves (age, 12 to 31 days).
Procedures—Calves were surgically instrumented with an abomasal cannula and were administered 4 treatments in randomized order: all-milk protein milk replacer, high-glucose high-bicarbonate OAE, high-glucose high-bicarbonate OAE containing glycine, and low-glucose OAE containing acetate and propionate. Abomasal luminal pH was measured with a miniature glass pH electrode prior to treatment administration and every second afterward for 24 hours.
Results—Feeding of orally administered milk replacer resulted in a rapid increase in mean abomasal luminal pH from 1.3 to 5.8, followed by a gradual decrease to preprandial values by 8 hours afterward (mean 24-hour pH, 3.2). High-glucose high-bicarbonate OAEs caused a large and sustained increase from 1.3 to 7.5 (mean 24-hour pH, 4.1 for the solution without glycine and 3.5 for the solution with glycine). In contrast, feeding of the acetate-containing OAE was followed by only a mild and transient increase (mean 24-hour pH, 2.1); luminal pH returned to preprandial values by 3 hours after ingestion.
Conclusions and Clinical Relevance—Ingestion of a bicarbonate-containing OAE resulted in sustained abomasal alkalinization in dairy calves. Because persistently high abomasal luminal pH may facilitate growth of enteropathogenic bacteria, administration of OAEs containing a high bicarbonate concentration (> 70mM) is not recommended for calves with diarrhea.
Objective—To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.
Design—Prospective controlled clinical trial.
Animals—20 lactating Holstein cows.
Procedures—Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra–high-performance liquid chromatography with mass spectrometric detection.
Results—For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.
Conclusions and Clinical Relevance—Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.
Objective—To determine elimination kinetics of tilmicosin in milk following intramammary administration in lactating dairy cattle.
Design—Prospective pharmacokinetic study.
Animals—6 lactating dairy cows.
Procedures—Following collection of baseline milk samples, 1,200 mg (4 mL) of tilmicosin was infused into the left front and right rear mammary glands of each cow. Approximately 12 hours later, an additional 1,200 mg of tilmicosin was infused into the left front and right rear glands after milking. Milk samples were then collected from each gland at milking time for 40 days. Concentration of tilmicosin was determined by means of ultraperformance liquid chromatography–mass spectrometry, and a milk withdrawal interval for tilmicosin was calculated on the basis of the tolerance limit method.
Results—Although there was considerable variation between glands, concentration of tilmicosin was high in milk from treated glands and had a long half-life in treated and untreated glands. Tilmicosin was detected in all treated glands for the entire 40-day study period and was detected in untreated glands for approximately 30 to 35 days.
Conclusions and Clinical Relevance—Findings indicated that tilmicosin should not be administered by the intramammary route in lactating dairy cows. Milk from all glands of any cows accidentally treated should be discarded for a minimum of 82 days following intramammary administration.
Objective—To determine the tissue depletion profile of tulathromycin and determine an appropriate slaughter withdrawal interval in meat goats after multiple SC injections of the drug.
Animals—16 healthy Boer goats.
Procedures—All goats were administered tulathromycin (2.5 mg/kg, SC) twice, with a 7-day interval between doses. Blood samples were collected throughout the study, and goats were euthanized at 2, 5, 10, and 20 days after the second tulathromycin dose. Lung, liver, kidney, fat, and muscle tissues were collected. Concentrations of tulathromycin in plasma and the hydrolytic tulathromycin fragment CP-60,300 in tissue samples were determined with ultrahigh-pressure liquid chromatography–tandem mass spectrometry.
Results—The plasma profile of tulathromycin was biphasic. Absorption was very rapid, with maximum drug concentrations (1.00 ± 0.42 μg/mL and 2.09 ± 1.77 μg/mL following the first and second doses, respectively) detected within approximately 1 hour after injection. Plasma terminal elimination half-life of tulathromycin was 61.4 ± 14.1 hours after the second dose. Half-lives in tissue ranged from 2.4 days for muscle to 9.0 days for lung tissue; kidney tissue was used to determine the withdrawal interval for tulathromycin in goats because it is considered an edible tissue.
Conclusions and Clinical Relevance—On the basis of the tissue tolerance limit in cattle of 5 ppm (μg/g), the calculated withdrawal interval for tulathromycin would be 19 days following SC administration in goats. On the basis of the more stringent guidelines recommended by the FDA, the calculated meat withdrawal interval following tulathromycin administration in goats was 34 days.
OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg).
ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers.
PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves.
RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.
Objective—To determine the elimination kinetics of
ceftiofur hydrochloride in milk after intramammary
administration in lactating dairy cows.
Animals—5 lactating dairy cows.
Procedure—After collection of baseline milk samples,
300 mg (6 mL) of ceftiofur was infused into the
left front and right rear mammary gland quarters of
each cow. Approximately 12 hours later, an additional
300 mg of ceftiofur was administered into the
same mammary gland quarters after milking. Milk
samples were collected from each mammary gland
quarter every 12 hours for 10 days. Concentrations of
ceftiofur and its metabolites in each milk sample
were determined to assess the rate of ceftiofur elimination.
Results—Although there were considerable variations
among mammary gland quarters and individual
cows, ceftiofur concentrations in milk from all treated
mammary gland quarters were less than the tolerance
(0.1 µg/mL) set by the FDA by 168 hours (7 days)
after the last intramammary administration of ceftiofur.
No drug concentrations were detected in milk
samples beyond this period. Ceftiofur was not detected
in any milk samples from nontreated mammary
gland quarters throughout the study.
Conclusions and Clinical Relevance—Ceftiofur
administered by the intramammary route as an extralabel
treatment for mastitis in dairy cows reaches
concentrations in milk greater than the tolerance set
by the FDA. Results indicated that milk from treated
mammary gland quarters should be discarded for a
minimum of 7 days after intramammary administration
of ceftiofur. Elimination of ceftiofur may be correlated
with milk production, and cows producing smaller
volumes of milk may have prolonged withdrawal
times. (J Am Vet Med Assoc 2004;224:1827–1830)
To determine the influence of stage of lactation on the pharmacokinetics in milk when multiple doses of meloxicam were administered alone or in combination with gabapentin to postpartum (PP) and mid-lactation (ML) cows.
8 postpartum and 8 mid-lactation dairy cows.
Cows were randomly divided into 2 groups (n = 8) which included 4 PP cows and 4 ML cows. Group I received only 6 oral daily doses of meloxicam (1.0 mg/kg for 6 doses). Group II received 6 oral daily doses of co-administered meloxicam (1.0 mg/kg) and gabapentin (20 mg/kg) for 6 doses. Meloxicam and gabapentin were quantified in plasma and milk samples by ultra–high-performance liquid chromatography–tandem mass spectrometry, and the pharmacokinetic analysis of milk and plasma was performed using a non-compartmental approach.
Regardless of lactation status, dairy cattle administered multiple doses of meloxicam and/or gabapentin showed low drug residue concentrations and little accumulation in milk. The terminal plasma half-life of meloxicam was significantly increased (P < .02) in PP cows (12.9 hr) compared to ML cows (9.4 hr). The apparent terminal half-life in milk for meloxicam and gabapentin was not affected by stage of lactation. Co-administration of gabapentin did not alter plasma or milk concentrations of meloxicam.
The results of this study suggest that milk from cows treated with multiple doses of meloxicam alone or in combination with gabapentin will have low drug concentrations and falls below our reported limit of detection for meloxicam or gabapentin 120 and 60 hours respectively, following the final dose regardless of their stage of lactation.