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General Orthopaedics

DURATION OF ANTIBIOTIC PROPHYLAXIS WITH INTRAVENOUS CEFUROXIME AFFECTS INFECTION RATE WITH STAPHYLOCOCCUS AUREUS IN AN OPEN FRACTURE MODEL IN RABBITS

European Bone and Joint Infection Society (EBJIS), Nantes, France, September 2017



Abstract

Aim

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.

Method

A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole-LCP and inoculated with Staphylococcus aureus (2×106 colony forming units, CFU per inoculum). This inoculum was previously shown to result in a 100% infection rate in the absence of any antibiotic 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. Blood samples were taken from rabbits preoperatively and on days 3, 7 and 14 after surgery to measure white blood cell count (WBC) and C-reactive protein (CRP) levels.

Results

Duration of PAP had a significant impact on the success of antibiotic prophylaxis. The single shot regimen completely failed to prevent infection. All samples (soft tissue, implant and bone) from this group displayed high numbers of bacteria. Additionally, abscesses were present in two of six rabbits. The 24-hour regimen showed a reduced infection rate (1 out of 6 rabbits infected), but only the 72-hour course was able to prevent FRI in all animals in our model. After an initial postoperative peak on day three, CRP levels then decreased to baseline (approx. 30 µg/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).

Conclusions

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.

Acknowledgements

This work was funded by AOTrauma


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