title: Levofloxacin and trovafloxacin inhibition of experimental fracture-healing.
abstract: We previously have shown that experimental fractures exposed to ciprofloxacin have diminished fracture healing. The purpose of this study was to assess the effect of levofloxacin and trovafloxacin on experimental fracture healing to test the hypothesis that diminished fracture healing is a quinolone class effect. Sixty-one male Wistar rats were divided into three groups, which received 25 mg/kg of levofloxacin twice daily for 3 weeks, 35 mg/kg of trovafloxacin twice daily for 3 weeks, or no treatment, beginning 7 days after production of closed, nondisplaced, bilateral femoral fractures. The mean peak serum concentrations of levofloxacin and trovafloxacin drawn 30 minutes after administration were 6.9 and 7.0 microg/mL, respectively. Radiographic, histologic, and biomechanical studies were used to evaluate fracture healing. Torsional strength testing of fracture callus exposed to levofloxacin and trovafloxacin revealed a decrease in strength (299 and 257 N-mm, respectively) as compared with controls (364 N-mm). Radiographs revealed significantly more advanced healing in control animals (Goldberg score of 2.1) compared with the fractures in the rats treated with levofloxacin and trovafloxacin (Goldberg score of 1.5 in both groups). Fracture calluses in the animals treated with levofloxacin and trovafloxacin showed a lower histologic grade (5.3 and 3.5, respectively) as compared with control animals (7.5) representing a less mature callus with the presence of more cartilage and less woven bone. These data suggest that experimental fractures systemically exposed to levofloxacin or trovafloxacin have diminished healing during the early stages of fracture repair. The administration of quinolones during early fracture repair may compromise fracture healing in humans.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Archie C
authors.initials: AC
authors.lastname: Perry
authors.forename: Branko
authors.initials: B
authors.lastname: Prpa
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rouse
authors.forename: Kerryl E
authors.initials: KE
authors.lastname: Piper
authors.forename: Arlen D
authors.initials: AD
authors.lastname: Hanssen
authors.forename: James M
authors.initials: JM
authors.lastname: Steckelberg
authors.forename: Robin
authors.initials: R
authors.lastname: Patel
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000503:physiopathology; D024841:Fluoroquinolones; D017102:Fracture Healing / Q000187:drug effects*; D064704:Levofloxacin; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D015242:Ofloxacin / Q000097:blood / Q000494:pharmacology*; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D064704:Levofloxacin; C080163:trovafloxacin; D015242:Ofloxacin