Pharmacokinetics of Intrauterine Ciprofloxacin in the Mare and Establishment of Minimum Inhibitory Concentrations for Equine Uterine Bacterial Isolates

Abstract Infectious endometritis can have a significant adverse impact on fertility of broodmares. Unfortunately, some Gram-negative bacteria cultured from the equine uterus are resistant to common antimicrobial agents (e.g., aminoglycosides). Fluoroquinolones could be an alternative for resistant Gram-negative bacteria; however, the commercial formulation of enrofloxacin has been reported to cause severe ulcerative hemorrhagic endometritis in mares following intrauterine infusion. The aim of the present study was to evaluate the pharmacokinetics of ciprofloxacin in the uterine lumen, endometrial tissue, and blood plasma following intrauterine infusion. Mares (n = 10) were evaluated by ultrasound and infused with 600 mg of undiluated ciprofloxacin (10 mg/mL) when in estrus. Intraluminal fluid samples and peripheral blood samples were collected at 10 minutes, 2, 4, 8, 12, and 24 hours postinfusion. Uterine biopsy samples were collected at 2 and 24 hours after infusion in three additional mares. Concentration of ciprofloxacin in endometrial tissue and the uterine lumen was 7,433.3 ± 4,027.1 μg/g and 2,487.1 ± 99.8 μg/mL, respectively, 2 hours after intrauterine infusion and 65.4 ± 31.5 μg/g and 91.2 ± 51.3 μg/mL, respectively, 24 hours after treatment (mean ±standard error of the mean). In contrast, the average plasma ciprofloxacin concentration was only 0.0723 ± 0.0749 μg/mL over the observation period. Minimum inhibitory concentration (MIC) and MIC 90 were determined for common bacterial species associated with equine endometritis. Ciprofloxacin concentrations remained above MIC 90 for Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa in the uterine lumen and endometrial tissue. Ciprofloxacin may be an appropriate option for treatment of infectious endometritis associated with susceptible bacterial organisms in the mare.