Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral and intravenous administration of marbofloxacin to turkeys (breed BUT 9; six animals per group) at a dose of 2 mg/kg of body weight (BW). At the same time, the serum concentrations of marbofloxacin were measured at different time intervals by a standardized high-performance liquid chromatography method, allowing the calculation of the most relevant kinetic parameters (PK parameters). The in vitro serum inhibitory activity of marbofloxacin against the selected E. coli strain, O78/K80, was 0.5 μg/ml in the blood serum of turkeys, and the ratio of the maximum concentration of the drug in serum to the serum inhibitory activity was 1.34. The lowest ratio of the measured serum concentration multiplied by the incubation period of 24 h to the serum inhibitory activity required for bacterial elimination was lower than the ratio of the area under the serum concentration-time curve (AUC) to the serum inhibitory activity. These first results suggested that the recommended dose of 2 mg/kg BW of marbofloxacin is sufficient to achieve a therapeutic effect in diseased animals. However, considering the risk of resistance induction, the applied dose should be equal to an AUC/MIC of >125, the generally recommended dose for all fluoroquinolones. According to the PK-PD results presented here, a dose of 3.0 to 12.0 mg/kg BW per day would be needed to meet this criterion. In conclusion, the results of the present study provide the rationale for an optimal dose regimen for marbofloxacin in turkeys and hence should form the basis for dose selection in forthcoming clinical trials.

Systemic therapy with oxytetracycline is often used for treatment of clinical metritis although data about its penetration into the uterus and uterine secretion are lacking. Uterine secretions and milk from six cows with clinical metritis were collected for microbiological assay. The animals were treated intramuscularly with long-acting oxytetracycline (20 mg/kg) and samples of plasma, milk and uterine secretions were collected for determination of the antibiotic concentrations by HPLC-PDA analysis. Pharmacokinetics of the antibiotic and in silico prediction of its penetration into the uterus were described. Trueperella pyogenes with MIC values of 16–64 µg mL⁻¹ was isolated (n of cows = 4) from uterine secretions. Oxytetracycline showed fast absorption and penetration in the uterine secretions and milk. No change of withdrawal time for milk was necessitated in cows with clinical metritis. Maximum levels in uterine secretions and predicted concentrations of oxytetracycline in the uterus were lower than MIC values. Systemic administration of long-acting oxytetracycline did not guarantee clinical cure and was not a suitable choice for treatment of clinical metritis associated with Trueperella pyogenes. The appropriate approach to antibiotic treatment of uterine infections of cows requires knowledge on penetration of the antibiotics at the site of infection and sensitivity of pathogens.

Puerperal metritis in cows is often treated with antibacterial drugs. The prudent use of antibiotics in farm animals requires state-of-the-art knowledge of their pharmacokinetics and data from sensitivity tests of pathogenic bacteria. Changes in oxytetracycline levels in the uterine secretion over time after intrauterine administration in cows with metritis were evaluated in relation to the sensitivity of pathogenic bacterial isolates. Oxytetracycline levels in plasma, milk and uterine secretion were determined via LC–MS/MS analysis. Pathogenic bacteria were isolated and their sensitivity to oxytetracycline was determined. The concentrations of oxytetracycline in the uterine secretion were 433.79 (39.17–1668.76) µg·mL⁻¹ six hours after the third application at a dose of 8 mg/kg and 84.33 (1.58–467.55) µg·mL⁻¹ 96 h after the last treatment. These levels were higher than the minimum inhibitory concentrations—namely, between 4 and 64 µg·mL⁻¹—against pathogenic isolates Trueperella pyogenes, Streptococcus intermedius, Escherichia coli and Bacillus pumilis. Higher concentrations over time were measured in milk rather than in plasma, indicating the need to monitor the withdrawal time for milk. The intrauterine infusion of oxytetracycline for three consecutive days resulted in the successful treatment of metritis in terms alleviating inflammation and restoring the estrus cycle in cows.