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The effect of fluoroquinolone antibiotics on growing cartilage in the lamb model
Jason M Sansone1, Norman J Wilsman, Ellen M Leiferman
1Department of Orthopedics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Insights
Fluoroquinolone antimicrobials did not impact growth velocity or cause cartilage damage in lambs. These findings suggest fluoroquinolones may be safe for pediatric use, warranting further clinical studies.
Area of Science:
- Pediatric pharmacology
- Antimicrobial research
- Skeletal development
Background:
- Fluoroquinolones are antimicrobials with broad-spectrum activity.
- Pediatric use is limited due to concerns about cartilage damage and growth inhibition.
- Previous animal studies suggest potential negative effects on growth, but human data are inconclusive.
Purpose of the Study:
- To investigate the effects of fluoroquinolones on epiphyseal plate cartilage and growth velocity in a pediatric-relevant animal model.
- To assess potential chondrotoxicity and growth inhibition associated with fluoroquinolone administration.
Main Methods:
- Gatifloxacin and ciprofloxacin were administered to lambs for 14 days at pediatric-equivalent doses.
- Growth velocity was determined using double fluorochrome labeling.
- Articular cartilage was analyzed macroscopically and microscopically for pathological changes.
Main Results:
- Neither gatifloxacin nor ciprofloxacin affected proximal tibial growth plate velocity.
- No significant differences in recumbent versus standing intervals were observed between treated and control lambs.
- Articular cartilage examination revealed no evidence of chondrotoxicity.
Conclusions:
- Fluoroquinolone antimicrobials do not inhibit growth velocity or cause chondrotoxicity in the ovine model at pediatric-relevant doses.
- These findings suggest that concerns regarding fluoroquinolone use in children may be unfounded.
- Further studies in various species, including humans, are warranted to confirm clinical safety.
Background:
The fluoroquinolones are a relatively new class of antimicrobials with an appealing spectrum of activity. Their use in pediatric medicine is limited because of the concern over possible growth inhibition, as published reports have documented articular cartilage damage in animal models after their administration. These data, extrapolated to include the epiphyseal cartilage, suggest that these agents may reduce growth rates, but limited human data are at the least equivocal, if not strictly contradictory to such claims. Specific investigations into the effects of fluoroquinolones on epiphyseal plate cartilage and growth velocity have not been performed.
Methods:
Gatifloxacin and ciprofloxacin were used as representative agents of the fluoroquinolone class. Each drug was administered to experimental lambs over a 14-day interval at a dose designed to reflect those used in pediatric medicine. Recumbent versus standing intervals were used to monitor for arthropathy. Upon completion of fluoroquinolone administration, lambs underwent double fluorochrome labeling for determination of growth velocity. Gross and microscopic analysis of articular cartilage was performed to assess for pathologic changes. Age- and sex-matched lambs served as controls.
Results:
Neither gatifloxacin nor ciprofloxacin negatively affected growth velocity of the proximal tibial growth plate as measured by double fluorochrome labeling. In addition, no difference between experimental and control lambs in regard to recumbent versus standing intervals was noted. Examination of the articular cartilage failed to suggest chondrotoxicity.
Conclusion:
Fluoroquinolone antimicrobials do not affect growth velocity in the ovine model when administered along a dosing regimen that closely models that seen in pediatric medicine.
Clinical Relevance:
Fluoroquinolones may be acceptable for use in the pediatric population, as concerns over chondrotoxicity and growth inhibition may not be valid. These data suggest that expanded studies in lambs and other species, including humans, with differences in dosing and duration are justified to ultimately demonstrate clinical safety.
