2003 Abstract : S4 – Haleem

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Authors: A.A. HALEEM, M.S. ROUSE, D.G. LEWALLEN, A.D. HANSSEN, J.M. STECKELBERG, & R. PATEL.

Title: The Effect of Gentamicin or Vancomycin on Experimental Fracture Healing

Address: Mayo Clinic, 200 1st St S.W., Rochester, MN 55900

Purpose: Quinolone antimicrobial agents have shown to impede experimental fracture healing. It is not known whether gentamicin or vancomicin impairs fracture healing. These antibiotics are used systemically for treating bone and joint infections and also mixed into polymethylmethacrylate for local delivery. It is important to have baseline knowledge of these drugs in relation to their effect on bone healing.

Methods: Using a rat model of implant stabilized non-displaced fractures, we studied the mechanical strength and radiological features of fracture healing after gentamicin or vancomycin treatment. Both femurs of 47 Wistar rats were stabilized by intramedullary rod placement and fractured on a three point bending device. Fracture type and location were verified radiologically. Beginning 7 days later, the rats received no treatment, gentamicin 1.5 mg/kg IM, or vancomycin 25 mg/kg IP, bid for 21 days. Twelve hours after the last treatment, the rats were sacrificed and the left femurs were harvested. Tissues were radiographed, femurs from 2 animals were processed for histological exam, and the remaining tissues were process for mechanical strength testing. Mechanical strength was determined by testing the bones to failure in torsion at room temperature on an electromagnetic testing machine at a rate of 1.25o/sec with no axial load. Torque and stiffness were calculated from a continuous X-Y plot. Results were expressed as mean torque and stiffness for each treatment group and analyzed by Student's t test. The mean 30 minute serum concentration of gentamicin and vancomycin were 4.5 and 35.1 mg/mL, respectively.

Results:

Treatment  No.  Torque  Torsional Rigidity  Mean Goldberg 
Group   Animals   Mean ± SE(N-mm)  Mean ± SE (N-mm/deg)  Radiological Scores 
No treatment  12   334 ± 44  40 ± 6   2.3 
Gentamicin  15  437 ± 30   50 ± 4  2.6 
Vancomycin  14   424 ± 36  56 ± 4   2.6 

Discussion: The torsional rigidity of experimental fracture callus after 21 days gentamicin exposure disclosed a 20% increase in torsional rigidity (P=0.37) when compared with 21 days of no treatment. The torsional rigidity of experimental fracture callus after 21 days vancomycin treatement disclosed a 29% increase in torsional rigidity (P=0.40) when compared with 21 days of no treatment.

Significance: We did not detect statistically significant differences in mechanical strength or radiological observations in experimental fractures from animals treated with gentamicin, vancomycin or no treatment. Whereas impaired fracture healing has been previously reported after quinolone treatment, this was not observed after vancomycin or gentamicin treatment.