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

Abstract

Summary 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.

Fluoroquinolone exposure in utero did not affect articular cartilage of resulting foals

“…While our concurrent study showed that enrofloxacin and its active metabolite (ciprofloxacin) cross the equine placenta without causing gross or histological lesions in foals born from mares treated during late pregnancy, 3…”

Clinical insights: Recent development in equine neonatology and foal medicine (2017–2019)

“…No gross or microscopic lesions were noted in the articular cartilage collected from the 5-week-old foals in either treatment groups nor were any differences in tendon strength noted between the treatment and control groups [18]. However, gross articular lesions were noted in multiple joints of the two positive control foals in the study; these foals were treated with 10 mg/kg of enrofloxacin per os, once daily for 7-10 days starting at 2 and 3 weeks of age [18]. In this complementary study, administration of enrofloxacin in late pregnant mares did not cause tendinopathies or articular damage in the resulting foals examined at 5 weeks of age.…”

“…As anticipated, detectable maternal plasma concentrations of enrofloxacin and ciprofloxacin were noted throughout the treatment period; unexpectedly, both of these drugs were still detectable in the amniotic and allantoic fluids 30 – 40 days after administration of the last oral dose of enrofloxacin. No gross or microscopic lesions were noted in the articular cartilage collected from the 5‐week‐old foals in either treatment groups nor were any differences in tendon strength noted between the treatment and control groups . However, gross articular lesions were noted in multiple joints of the two positive control foals in the study; these foals were treated with 10 mg/kg of enrofloxacin per os, once daily for 7 – 10 days starting at 2 and 3 weeks of age .…”

“…Other antimicrobials such as ceftiofur sodium and ceftiofur crystalline free acid can be used in the pregnant mare, but do not reliably cross the equine placenta . Recently, Equine Veterinary Journal published two manuscripts examining enrofloxacin in pregnant mares, fetal fluids and fetuses as well as the impact of enrofloxacin administration to pregnant mares on fetal cartilage . Enrofloxacin undergoes hepatic metabolism into ciprofloxacin or is excreted unchanged in the urine, but both enrofloxacin and ciprofloxacin are effective against a variety of equine pathogens.…”

“…In a follow‐up study, the same group of investigators evaluated cartilage and tendon strength of 5‐week‐old foals that were born from mares administered enrofloxacin at 280 days gestation utilising dosages of 7.5 mg/kg, per os and 15 mg/kg, per os, once daily for 14 consecutive days . Fetal fluids were collected 30 – 40 days after the last enrofloxacin dose was administered to determine if residual amounts of enrofloxacin could be detected post‐administration.…”