Administration of enrofloxacin during late pregnancy failed to induce lesions in the resulting newborn foals.

BACKGROUND: A recent study demonstrated that enrofloxacin and ciprofloxacin cross the equine placenta without causing gross cartilage or tendon lesions in the 9-month fetus; however, long-term effects of in utero fluoroquinolone exposure remain unknown. OBJECTIVES: To assess effects of fetal exposure to enrofloxacin on the resulting foal's cartilage and tendon strength. STUDY DESIGN AND METHODS: Healthy mares at 280 days' gestation were allocated into four groups: untreated (n = 5), therapeutic treatment (7.5 mg/kg enrofloxacin, PO × 14 days, n = 6), supratherapeutic treatment (15 mg/kg, PO × 14 days, n = 6) and no mare treatment with treatment of the foals post-partum (n = 2). Mares were allowed to carry pregnancy to term, and foals were maintained on pasture for 5 weeks. After that foals were euthanized, and their articular cartilage and extensor and flexor tendons were examined macroscopically and histologically for lesions. Tendon strength was tested by loading until failure. RESULTS: Administration of enrofloxacin at recommended doses in late gestation did not result in cartilaginous lesions or clinical lameness in any foal by 5 weeks old. Tensile strength was greater in hind tendons than front tendons, but no difference was found between foals born from treated and control mares. Expectedly, osteochondral changes were present both in foals born from enrofloxacin-treated mares and in negative control foals with no apparent association with fluoroquinolone treatment during pregnancy. MAIN LIMITATIONS: Only one time point in gestation was evaluated, and mares treated in the study were healthy at time of treatment. Additionally, it is possible that the assessments performed herein were not sensitive enough to detect subtle or functional changes in the articular cartilage. Further studies are needed to determine if enrofloxacin administration during late pregnancy potentiates osteochondral alterations in the first year of life. CONCLUSIONS: While this study did not assess other stages of gestation or long-term foal outcomes, short-term administration of enrofloxacin to late gestation mares did not result in macroscopic or microscopic lesions in the resulting foals by 5 weeks of age.

Diffusion of fluoroquinolones into equine fetal fluids did not induce fetal lesions after enrofloxacin treatment in early gestation.

While recent work demonstrated that enrofloxacin and ciprofloxacin reach the fetoplacental unit without causing obvious lesions in the 9-month-old equine fetus or resulting foal, many practitioners still hesitate to prescribe a fluoroquinolone during pregnancy. Since early gestation is a critical time for fetal skeletal development, if fluoroquinolones are chondrotoxic to the fetus at any point during gestation, this period would be important. The aim of this study was to assess the effects of 2 weeks' exposure to enrofloxacin on the equine fetus between 46 and 60 days gestation. Twelve pregnancies from nine healthy mares were allocated into two groups: untreated (n=7), or treatment (7.5mg/kg enrofloxacin, PO×14days, n=6). Abortion was induced with prostaglandin 24h after the last enrofloxacin dose, or on the equivalent day of gestation for untreated mares. Four of nine mares were rebred for a second cycle and were assigned to the opposite treatment to serve as their own controls. Fetal fluids from treated mares were analysed for enrofloxacin and ciprofloxacin concentrations. Fetal organs (heart, lungs, spleen, kidney, and liver) and limbs were examined histopathologically. Enrofloxacin and ciprofloxacin diffused to the fetal fluids during early gestation and did not result in detectable abnormalities in the fetus after 14 days of treatment. While current research does not determine long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.

Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares.

BACKGROUND: In selective cases, enrofloxacin may be an alternative antibacterial agent to treat unresponsive infections in pregnant mares. Supratherapeutic doses of enrofloxacin are toxic to adult horses and also to newborn foals, however, it is unknown if enrofloxacin crosses the equine placenta or if it is toxic to the fetus. OBJECTIVES: To assess the diffusion of enrofloxacin and its metabolite to fetal fluids and its effects on fetal cartilage when administered to pregnant mares. STUDY DESIGN: In vivo and terminal controlled experiment. METHODS: Healthy mares at 260 days of gestation were allocated into three groups: untreated (n = 3), therapeutic treatment (5 mg/kg enrofloxacin, i.v., n = 7) or supratherapeutic treatment (10 mg/kg, i.v., n = 6) for 11 days. Fetal fluids were collected on days 1, 5 and 11 of treatment. Premature delivery was induced on day 11 with oxytocin and fetal fluids and plasma were collected during delivery. Plasma and fetal fluid enrofloxacin and ciprofloxacin concentrations were measured by liquid chromatography-mass spectrometry. Fetal articular cartilage was examined macroscopically and histologically for lesions. RESULTS: Enrofloxacin and ciprofloxacin reached the minimum inhibitory concentrations for common pathogens in all fluids. Ciprofloxacin did not increase with the double enrofloxacin dose in maternal plasma, but allantoic fluid showed a 10-fold increase relative to fetal trough plasma concentrations. Administration of enrofloxacin at recommended doses did not result in cartilaginous lesions in fetuses. MAIN LIMITATIONS: Only one time point in gestation was evaluated and mares treated in the study were healthy at the time of treatment. It remains to be determined if enrofloxacin shows toxicity at other stages of pregnancy, after a longer duration of treatment, or once the foals are delivered and articular surfaces are weightbearing. CONCLUSIONS: Short-term administration of enrofloxacin to late gestation mares resulted in detectable enrofloxacin and ciprofloxacin concentrations in fetal fluids and did not result in macroscopic or microscopic lesions in the fetus. While further research is needed to address long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.

Canine intrathoracic sarcoma with ultrastructural characteristics of human synovial sarcoma - case report.

BACKGROUND: Canine joint sarcomas, designated synovial sarcomas, are uncommon malignant mesenchymal neoplasms that occur in the large joints of the extremities of middle-aged, large-breed dogs. We report the diagnosis of an intrathoracic sarcoma with ultrastructural characteristics reminiscent of human synovial sarcoma in a dog. CASE PRESENTATION: A 7-year-old female spayed Tibetan terrier crossbred dog was presented for acute severe labored breathing and diagnosed with an intrathoracic neoplastic mass. The neoplasm resulted in the accumulation of substantial amounts of viscous pleural fluid that led to dyspnea. The neoplastic mass consisted of interweaving bundles of large pleomorphic mesenchymal cells, supported by an alcian blue positive myxomatous matrix. The neoplastic cells were immunohistochemically negative for cytokeratin and CD18. Transmission electron microscopy indicated that the neoplastic cells had desmosome junctions, short microvilli-like structures and ample amounts of rough endoplasmic reticulum resembling type B-like synoviocytes and synovial sarcoma as reported in people. Despite complete surgical excision of the neoplastic mass, clinical signs recurred after a month and led to the euthanasia of the dog. CONCLUSION: Currently, there are no immunohistochemical markers specific for synovial sarcoma. Canine neoplasms with transmission electron microscopy characteristics resembling type B-like synoviocytes should be considered similar to the human sarcomas that carry the specific translocations between chromosomes X and 18.