Aim. Duration of perioperative antimicrobial prophylaxis (PAP) remains controversial in prevention of fracture-related infection (FRI) – with rates up to 30% - in open fracture (OF) management. Objectives were to investigate the impact of the PAP duration exclusively in or related to long bone OF trauma patients and the influence of augmented renal clearance (ARC), a known phenomenon in trauma patients, as PAP consists of predominantly renally eliminated antibiotics. Method. Trauma patients with operatively treated OF, admitted between January 2003 and January 2017 at the University Hospitals Leuven, were retrospectively evaluated. FRI was defined following the criteria of the consensus definition of FRI. A logistic regression model was conducted with FRI as outcome. Results were considered statistically significant when p< 0.05. Results. Forty (8%) from the 502 patients developed a FRI, with 20% FRIs in Gustilo-Anderson (GA) III OFs. Higher GA grade and polytrauma were independently associated with the occurrence of FRI. The heterogeneity in OF management, especially with regard to the applied PAP regimens and duration, was striking and consequently hampering the investigation on the impact of PAP duration. To overcome this issue, a subgroup analysis was performed in patients treated with the two PAP regimens as defined in the hospitals' guidelines – i.e. cefazolin, with metronidazole and tobramycine when extensive contamination was present -, revealing flap coverage and relative duration of augmented renal ARC as independently associated factors. Conclusions. For the first time, a definition based on diagnostic criteria was used to objectively include patients with a FRI. In order to support clinicians in establishing strategies to prevent FRI in long bone OFs, further prospective large randomized controlled trials with clearly predefined PAP regimens are needed to provide reliable recommendations regarding the impact of duration of PAP and ARC

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