The objective was to determine the effect of milking frequency and dosing interval on pharmacokinetics of cephapirin after intramammary infusion. Six healthy Holstein cows were administered cephapirin (200 mg) into 1 rear mammary gland after each of 2 milkings. Cows were milked twice daily (2x) and dosed at a 12-h interval or 3 times daily (3x) and dosed at an 8- or 16-h interval. A duplicated Latin square design allowed each cow to receive all 3 frequency-dose treatments, with intervening washout periods. Concentrations of cephapirin (CEPH) and desacetylcephapirin (DAC) in milk from the treated glands were determined at each milking after infusion using liquid chromatography-mass spectrometry. Data were fitted using 1- and 2-compartment pharmacokinetic models, as well as a noncompartmental model. Cephapirin was rapidly metabolized to DAC in the mammary gland, with DAC being the predominant agent in milk until 48 h after infusion. Pharmacokinetics of CEPH and DAC were similar for all treatment groups, with a 1-compartment model providing a better fit than a 2-compartment model in most instances. Milking frequency did not affect the length of time that milk CEPH concentration exceeded MIC(50) or MIC(90) values (the minimum inhibitory antimicrobial concentration needed to inhibit 50 or 90% of microbial activity, respectively) for common mastitis pathogens, except that cows milked 3x and dosed at a 16-h interval maintained inhibitory concentrations approximately 8 h longer than those dosed at an 8-h interval. Time for milk CEPH concentration to reach the FDA tolerance did not differ among treatment groups [mean +/- SD; 68 +/- 20, 66 +/- 22, and 57 +/- 18 h after last treatment for cows treated at 12, 16, and 8 h, respectively]. Mean residence time for CEPH in the mammary gland was linearly and negatively associated with the volume of milk produced. Calculated CEPH concentration in composite milk from all 4 mammary glands was below the FDA tolerance in all cows by 96 h after the last infusion, which is the labeled withholding time for the preparation used. Our findings suggest that this CEPH preparation, which is labeled for 2 doses 12 h apart, could be administered at a 16-h interval in herds milking 3x, with no significant effect on inhibitory concentrations in milk or withdrawal time; extended withdrawal times would be prudent for cows with very low milk production. Further investigation is needed to determine if milking frequency affects CEPH pharmacokinetics in cows with clinical mastitis.

Clinical mastitis in dairy cows is commonly treated with intramammary (IMM) antimicrobial agents. Pharmacokinetic data are used to design treatment regimens and determine withholding times. In some pharmacokinetic studies, investigators measure antimicrobial concentrations in foremilk, whereas in others, they use bucket milk or do not specify the milk fraction sampled. Our objective was to compare antimicrobial concentrations in foremilk, bucket milk, and strippings after IMM treatment of six healthy Holsteins. One mammary gland/cow was infused with 200 mg of cephapirin (CEPH) after each of the two milkings, using different milking frequencies and treatment intervals in a randomized crossover design. Treated glands were sampled at the first milking following each infusion. Antimicrobial concentrations in milk were measured using HPLC/MS/MS. CEPH concentration was higher in foremilk (geometric mean 44.2 microg/mL) than in bucket milk (15.7 microg/mL) or strippings (18.5 microg/mL), as it was true for desacetylcephapirin (DAC) (59.5, 23.0, and 30.2 microg/mL, respectively). This finding, which was based on milk samples collected at the first milking after IMM infusion, suggests that pharmacokinetic data based on drug concentrations in foremilk may be misleading. Strippings were more representative of bucket milk than foremilk. The relationship between milk fraction and antimicrobial concentration should be investigated for other IMM antimicrobial agents. Meanwhile, it is essential that pharmacokinetic and residue studies report the fraction of milk that was analyzed.

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The transition from a high forage to a high concentrate diet is an important milestone for beef cattle moving from a stocker system to the feedlot. However, little is known about how this transition affects the rumen epithelial gene expression. This study assessed the effects of the transition from a high forage to a high concentrate diet as well as the transition from a high concentrate to a high forage diet on a variety of genes as well as ruminal papillae morphology in rumen fistulated Jersey steers. Jersey steers (n = 5) were fed either a high forage diet (80% forage and 20% grain) and transitioned to a high concentrate diet (20% forage and 80% grain) or a high concentrate diet (40% forage and 60% grain) and transitioned to a high forage diet (100% forage). Papillae from the rumen were collected for histology and RT‐qPCR analysis. Body weight had a tendency for significant difference (p = .08). Histological analysis did not show changes in papillae length or width in steers transitioning from a high forage to a high concentrate diet or vice versa (p > .05). Genes related to cell membrane structure (CLDN1, CLDN4, DSG1), fatty acid metabolism (CPT1A, ACADSB), glycolysis (PFKL), ketogenesis (HMGCL, HMGCS2, ACAT1), lactate/pyruvate (LDHA), oxidative stress (NQO1), tissue growth (AKT3, EGFR, EREG, IGFBP5, IRS1) and the urea cycle (SLC14A1) were considered in this study. Overall, genes related to fatty acid metabolism (ACADSB) and growth and development (AKT3 and IGFBP5) had a tendency for a treatment × day on trial interaction effect. These profiles may be indicators of rumen epithelial adaptations in response to changes in diet. In conclusion, these results indicate that changes in the composition of the diet can alter the expression of genes with specific functions in rumen epithelial metabolism.

Maternal antibodies interfere with BRSV vaccine responses and efficacy in young calves. The objective of this study was to determine if vaccination before the complete absorption of colostral antibodies results in adequate immune priming and clinical protection of beef calves. Within 6 h of life, calves were randomly assigned to 2 different treatment groups. Group Vacc (n = 25) received a single dose of a modified-live virus (MLV) BRSV vaccine intranasally (IN) and group Control (n = 25) received 2 mL of 0.9% saline IN. At approximately 3 months of age, all calves were experimentally challenged with BRSV. Serum and nasal secretion samples were collected before and after challenge for BRSV real-time RT-PCR and antibody testing. Respiratory signs were not observed before challenge. After challenge, respiratory scores were similar between groups. On the challenge day, >40% of calves in each group were febrile. The mean serum and nasal BRSV-specific antibody titers indicated natural BRSV exposure before the experimental challenge in both groups. All calves tested positive for BRSV and had a similar duration of shedding after challenge. Based on these results, vaccination at birth does not offer advantages for immune priming or clinical protection for beef calves in BRSV-endemic cow-calf herds.