Staphylococcus aureus (S. aureus) is a common pathogen that causes mastitis, an infection of the milk-secreting tissue of the udder, in dairy cows, and presents a huge economic problem for the dairy industry worldwide. Thus, control and treatment of mastitis in dairy cows is vital in order to reduce the costs associated with the disease. The main purpose of the current work was to examine the current dosage of rifaximin for the treatment mastitis in cows caused by S. aureus using pharmacokinetic/pharmacodynamic integration in a mouse mastitis model. The mouse mastitis model was established via injection of S. aureus Newbould 305 (400 CFU/gland) into the mouse mammary gland. A single dose of 50, 100, 200, or 400 μg/gland, administered via intramammary infusion, was used to study the pharmacokinetics of rifaximin. The pharmacokinetic parameters were analyzed by non-compartment and non-linear mixed-effect models using Phoenix software (version 8.1; Pharsight, USA). In vivo pharmacodynamics was used to examine 18 therapeutic regimens covering various doses ranging from 25 to 800 μg/gland and three dosing intervals of 8, 12, and 24 h per 24 h experiment cycle. The antibacterial effect of rifaximin was elevated with higher concentrations of rifaximin or shorter intervals of administration. The percentage of time that drug concentrations exceeded the MIC during a dose interval (%T > MIC) was generally 100% for rifaximin and was not better than AUC₂₄/MIC in the sigmoid E_max model of inhibitory effect. The optimal antibacterial effect was 2log₁₀CFU/gland when the magnitude of AUC₂₄/MIC reached 14,281.63 h. A total of 14,281.63 h of AUC₂₄/MIC was defined as a target value in the Monte Carlo simulation. The clinically recommended dosage regimen of 100 mg/gland every 8 h in 1 day achieved an 82.97% cure rate for the treatment of bovine mastitis caused by Staphylococcus aureus infection.

Deltamethrin, an important pyrethroid insecticide, is frequently detected in human samples. This study aims to assess the potential effects of deltamethrin on human health and investigate the patterns of residue enrichment and elimination in 112 healthy laying hens. These hens were administered 20 mg·kg⁻¹ deltamethrin based on their body weight. Gas chromatography-mass spectrometry (GC-MS) was used to investigate the residue enrichment pattern and elimination pattern of deltamethrin in the hens. The results indicated a significant increase in the concentration of deltamethrin in chicken manure during the treatment period. By the 14th day of administration, the concentration of deltamethrin in the stool reached 13,510.9 ± 172.24 μg·kg⁻¹, with a fecal excretion rate of 67.56%. The pulmonary deltamethrin concentration was the second highest at 3844.98 ± 297.14 μg·kg⁻¹. These findings suggest that chicken feces contain substantial amounts of deltamethrin after 14 days of continuous administration, and that it can easily transfer to the lungs. After 21 days of drug withdrawal, the residual concentration of deltamethrin in the fat of laying hens was 904.25 ± 295.32 μg·kg⁻¹, with a half-life of 17 days and a slow elimination rate. In contrast, the lungs showed relatively low elimination half-lives of 0.2083 days, indicating faster elimination of deltamethrin in this tissue. These results highlight differences in the rate of deltamethrin elimination in different tissues during drug withdrawal. The fat of laying hens exhibited the highest residue of deltamethrin and the slowest elimination rate, while the lungs showed the fastest elimination rate. Moreover, deltamethrin was found to accumulate in the edible tissues of eggs and laying hens, suggesting that humans may be exposed to deltamethrin through food.

In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the residue depletion of imidocarb (IMD) in bovine tissues, and the drug withdrawal time of IMD was determined. Twenty-five clinically healthy cattle (body weight 300 kg ± 15 kg) were randomly divided into five groups of five cattle each. The cattle were treated subcutaneously injecting a single dose of a generic IMD formulation, at the recommended dosage of 3.0 mg/kg. The five groups of cattle were slaughtered respectively at 96, 160, 198, 213, and 228 days after IMD administration. Samples from the liver, kidney, muscle, fat, and injection site were collected from each animal. After subtilis proteinase was used to digest the tissue, the content of IMD in the samples was analyzed by UPLC-MS/MS method. In conclusion, the method validation results showed that the method meets the criteria, and the longest withdrawal time of 224 days for the liver can be selected as the conclusive withdrawal time to guarantee consumer safety.

Imidocarb (IMD) is commonly used for treatment of eperythrozoon, babesia, piroplasma and trypanosoma in animals, but there are few studies on its pharmacokinetics in cattle. The purpose of this study was to obtain pharmacokinetic parameters and assess the bioequivalence of subcutaneous injections of two IMD formulations in cattle. Forty-eight healthy cattle, 24 males and 24 females, were randomLy divided into two groups (test group and reference group) with 12 males and 12 females per group. The generic IMD was injected subcutaneously with a single dose of 3.0 mg/kg in the test group. Reference group animals were given one injection of the marketed IMD at the same dosage. The limit of detection (LOD) and limit of quantification (LOQ) for IMD in cattle plasma were 0.05 ng/mL and 0.1 ng/mL, respectively. The recoveries ranged from 88.50% to 92.42%, and the equation of this calibration curve was Y = 13672.1X+187.43. The pharmacokinetics parameters of the test group showed that the maximum concentration of 2257.5±273.62 ng/mL was obtained at 2.14±0.67 h, AUC_0-t 14553.95±1946.85 ng·h/mL, AUC_∞ 15077.88±1952.19 ng·h/mL, T_1/2 31.77±25.75 h, CL/F 0.14±0.02 mL/h/g, and V_z/F 6.53±5.34 mL/g. There was no significant difference in AUC_0-t, AUC_∞ and C_max between the test group and the reference group (P>0.05). The 90% confidence interval of AUC_0-t, AUC_0-∞ and C_max in the test group was included in 80%–125% AUC_0-t, AUC_0-∞ and 70%–143% C_max in the reference group, respectively. Based on these results, the two preparations were found to be bioequivalent.

Dairy manure is a nutrition source for cropland soils and also simultaneously serves as a contamination source of antibiotic resistance genes (ARGs). In this study, five classes of antibiotics including aminoglycosides, beta-lactams, macrolides, sulfonamides, and tetracyclines, were spiked in dairy manure and incubated with soil for 60 days. The high throughput qPCR and 16S rRNA amplicon sequencing were used to detect temporal shifts of the soil antibiotic resistomes and bacterial community. Results indicated dairy manure application increased the ARG abundance by 0.5–3.7 times and subtype numbers by 2.7–3.7 times and changed the microbial community structure in soils. These effects were limited to the early incubation stage. Selection pressure was observed after the addition of sulfonamides. Bacterial communities played an important role in the shifts of ARG profiles and accounted for 44.9% of the resistome variation. The incubation period, but not the different antibiotic treatments, has a strong impact on the bacteria community. Firmicutes and Bacteroidetes were the dominant bacterial hosts for individual ARGs. This study advanced our understanding of the effect of dairy manure and antibiotics on the antibiotic resistome in soils and provided a reference for controlling ARG dissemination from dairy farms to the environment.