gms | German Medical Science

Objectives: Open fractures still have a high risk for Fracture Related Infection (FRI). The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial due to heterogeneous guidelines and highly variable prophylactic regimens in clinical practice. In order to provide further evidence with which to support the selection of antibiotic duration for open fracture care, we performed a preclinical evaluation in a contaminated rabbit fracture model.

Methods: A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole-LCP and inoculated with Staphylococcus aureus in an amount (2x10⁶ per inoculum) that was tested to result in 100% infection rate without prophylaxis. Cefuroxime was administered intravenously in a weight-adjusted dosage equivalent to human medicine (18.75 mg/kg) as a single shot only, for 24 hours (every 8 hours) and for 72 hours (every 8 hours) in separate groups of rabbits (n=6 per group). Infection rate per group was assessed after two weeks by quantitative bacteriological evaluation of soft tissue, bone and implants (lower limit of detection 100 CFU per sample). Blood samples were taken from rabbits preoperatively and on days 3, 7 and 14 after surgery (outcomes: white blood cell count (WBC) and C-reactive protein (CRP) levels). Radiographs of the operated limb were taken postoperatively and then weekly.

Results:

Duration of PAP had a significant impact on the success of antibiotic prophylaxis. The single shot regimen completely failed to prevent infection. All cultured tissue samples from the corresponding group (soft tissue, implant and bone) displayed high numbers of bacteria (see figure 1A). Aditionally, abscesses were present in two of six rabbits in that group. The 24 hours regimen showed a reduced infection rate (1 out of 6 rabbits infected, figure 1B), but only the 72 hour course was able to prevent FRI in all animals in our model (figure 1C).

CRP levels in all three study groups were typically elevated on post-operative day three, which is attributed to the surgical procedure. CRP levels then decreased to baseline (approx. 30 ug/ml) in the 24h-group and 72h-group, but remained significantly higher in the single shot group at day 7 and 14 (p<0.05). Other clinical observations between the study groups were not significantly different.

Conclusion:

When contamination with high bacterial loads is likely (e.g. in an open fracture situation), a 72-hour course of intravenous cefuroxime appears to be superior in preventing FRI compared to a single shot or 24-hour antibiotic regimen.