Distribution of amoxicillin and clavulanic acid in the uterus of healthy and metritic cows after intramuscular injection

Metritis in dairy cows is associated with reduced animal welfare and significant economic losses. Although a combination of amoxicillin-trihydrate and clavulanic acid is approved for metritis treatment in Germany, data on the pharmacokinetics and uterine distribution is lacking. This study evaluated drug concentrations after systemic and local therapy with focus on uterine concentrations of both substances in postpartum dairy cows. A total of 24 cows received amoxicillin-trihydrate and clavulanic acid (4:1 ratio) intramuscularly at a dose of 8.75 mg/kg bodyweight according to the approved label, on average 9 d postpartum. Of these, 12 cows were clinically healthy and 12 were diagnosed with metritis. An additional group of 6 cows with metritis received a single intrauterine dose of one 800 mg amoxicillin tablet. Uterine swabs were collected for bacteriological analysis and determination of minimum inhibitory concentrations (MICs). Plasma, lochia, and uterine tissue samples were collected at defined time points, and drug concentrations were quantified by HPLC-MS/MS. After intramuscular administration, mean maximum amoxicillin concentrations were observed in plasma (0.75 µg/mL) and lochia (4.07µg/g) at 4 h, and uterine tissue (1.38 µg/g) at 2 h after treatment. Intrauterine application resulted in higher local concentrations for lochia (431.09 µg/g) and tissue (73.46 µg/g) at 2 h. Measured concentrations exceeded MICs for Trueperella pyogenes (0.05 µg/mL) in all matrices following intramuscular and local treatment. However, the MIC for Escherichia coli (4.43 µg/mL), a major pathogen for metritis, was not reached at any time point after systemic administration. In contrast, intrauterine treatment achieved effective concentrations against E. coli in lochia throughout the sampling period and in tissue for most of the observed time. These findings question the suitability of intramuscular amoxicillin-clavulanic acid in this formulation as antimicrobial treatment for metritis associated with E. coli.