ANTIBIOTICS DURING FRACTURE HEALING: WHICH ONES ARE SAFE? AN EXPERIMENTAL STUDY

Abstract

Aim: Antibiotics are currently used during fracture healing for prevention or treatment of infection. Quinolones are well known to delay fracture healing, but little is known about other antibiotics. Cefazolin is the most commonly used drug for antibiotic prophylaxis, but many centres use cefuroxime. When allergy to cephalosporins is present, current recommendations include clindamicin or vancomicin. The purpose of this study is to know if other commonly used antibiotics can delay fracture healing.

Methods: 100 male 3-months-old Wistar rats were used. After anaesthesia with ketolar, a closed fracture in the middle third of the femur was carried out. Rats were divided in five groups (20 rats each): one receiving cefazolin (a first generation cephalosporin, CZ), other receiving cefuroxime (a second generation cephalosporine, CF), other vancomicin (group V), other clindamicin (group CL) and the other receiving placebo (P) for 4 weeks. Group CZ received a subcutaneous dose of 50mg/kg/daily, Group CF received a dose of 100 mg/Kg/daily, Group V received a dose of 20 mg/Kg/daily, Group CL received a dose of 25 mg/Kg/daily and group P received water. 4 weeks later rats were killed and femora extracted. A mechanical test (low speed torsion) was performed to evaluate healing. All four groups (CZ, CF, V, CL) were compared to placebo through ANOVA.

Results: Six bones were discarded because of technical errors, no infections were found. The maximum torque achieved by the calluses before breaking were 240 mNm in group P (n=18), 238 in group CZ (n=20), 178 in group CF (n=19), 167 in group V (n=19), and 205 in group CL (n=18). When compared to placebo, cefazolin and clindamicin showed no statistical differences (N.S, p> 0,10), vancomicin had lower callus strength (p=0,015), and cefuroxime had also lower callus strength near the significance level (p=0,084).

Conclusion: The mechanical strength of fracture callus is similar when rats are given cefazolin or clindamicin during fracture healing. The mechanical strength of fracture callus is lower when vancomicin (and probably cefuroxime) is given. If these results are similar to human, cefazolin and clindamicin are safe drugs to use during fracture healing. If possible, vancomicin (and perhaps cefiuroxime) use during fracture healing should be restricted.