Abstract
This work aimed to characterize the mammary gland pharmacokinetics of cefquinome after an intramammary administration and integrate pharmacokinetic/pharmacodynamic model. The pharmacokinetic profiles of cefquinome in gland tissue were measured using high performance liquid chromatograph. Therapeutic regimens covered various dosages ranging from 25 to 800 μg/gland and multiple dosing intervals of 8, 12, and 24 h. The in vivo bacterial killing activity elevated when dosage increased or when dosing intervals were shortened. The best antibacterial effect was demonstrated by a mean 1.5 log10CFU/gland visible count reduction. On the other hand, the results showed that the percentage of time duration of drug concentration exceeding the MIC during a dose interval (%T > MIC) was generally 100% because of the influence of drug distribution caused by the blood-milk barrier. Therefore, pharmacokinetic/pharmacodynamic parameter of the ratio of area under the concentration-time curve over 24 h to the MIC (AUC0-24/MIC) was used to describe the efficacy of cefquinome instead of %T > MIC. When the magnitude of AUC0-24/MIC exceeding 16571.55 h⋅mL/g, considerable activity of about 1.5 log10CFU/g gland bacterial count reduction was observed in vivo. Based on the Monte Carlo simulation, the clinical recommended regimen of three infusions of 75 mg per quarter every 12 h can achieve a 76.67% cure rate in clinical treatment of bovine mastitis caused by Staphylococcus aureus infection.
Highlights
Staphylococcus aureus is a common Gram-positive bacterium that frequently causes a variety of infections in humans and animals and is the primary pathogen responsible for bovine mastitis
S. aureus mastitis can lead to significant economic loss to the dairy industry due to the deterioration of milk quality, veterinary medicine expenses, and prohibitive labor costs (Gruet et al, 2001)
S. aureus can be isolated from the mammary gland (MG) tissue of all forms of mastitis because these organisms are capable of hiding in host phagocytes and mammary epithelial cell to avoid antibiotic effect (Hebert et al, 2000)
Summary
Staphylococcus aureus is a common Gram-positive bacterium that frequently causes a variety of infections in humans and animals and is the primary pathogen responsible for bovine mastitis. S. aureus mastitis can lead to significant economic loss to the dairy industry due to the deterioration of milk quality, veterinary medicine expenses, and prohibitive labor costs (Gruet et al, 2001). According to the clinical features, intramammary infection (IMI) is classified as clinical and subclinical mastitis. Clinical mastitis is acute and severe and may cause cow’s death. Dose Assessment of Cefquinome in Mastitis Treatment subclinical mastitis is generally not lethal, but can lead to huge financial losses. S. aureus can be isolated from the mammary gland (MG) tissue of all forms of mastitis because these organisms are capable of hiding in host phagocytes and mammary epithelial cell to avoid antibiotic effect (Hebert et al, 2000)
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