The effect of fluoroquinolone antibiotics on growing cartilage in the lamb model.
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Department of Orthopedics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Jason M
JM
Sansone
Norman J
NJ
Wilsman
Ellen M
EM
Leiferman
James
J
Conway
Paul
P
Hutson
Kenneth J
KJ
Noonan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D002358:Cartilage, Articular / Q000187:drug effects* / Q000254:growth & development; D002648:Child; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000633:toxicity*; D000077734:Gatifloxacin; D006132:Growth Plate / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008297:Male; D023421:Models, Animal; D012756:Sheep; D013977:Tibia / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D005456:Fluorescent Dyes; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D000077734:Gatifloxacin