Background. Surgical site infection following spine surgery is associated with increased morbidity, mortality and increased cost for the health care system. The reported pooled incidence is 3%. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and often involve the lumbar spine. Accordingly, the objective was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column of the same lumbar vertebra using microdialysis in an experimental porcine model. Method. The lumbar vertebral column was exposed in 8 female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously over 10 min. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. Microdialysis is a catheter-based pharmacokinetic tool, that allows dynamic sampling of unbound and pharmacologic active fraction of drugs e.g., cefuroxime. The primary endpoint was the time with cefuroxime above the clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL as this has been suggested as the best predictor of efficacy for cefuroxime. The secondary endpoint was tissue penetration (AUC. tissue. /AUC. plasma. ). Results. Mean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105–141) in plasma, 97 min (79–115) in the anterior column and 93 min (75–111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40–0.56) and posterior column 0.40 (0.33–0.48). Conclusions. Open lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime resulted in comparable T>MIC between the anterior and posterior column of the lumbar spine. Mean cefuroxime concentrations decreased below the clinical breakpoint MIC for S. aureus of 4 µg/mL after 123 min (plasma), 97 min (anterior column) and 93 min (posterior column). This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours

Aim. Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). Method. In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). Results. During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. Conclusions. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Acknowledgments. We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study. This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020]

Aim. Cefuroxime is a time-dependent antibiotic widely used as intravenous perioperative prophylaxis in spine surgery. A previous study has indicated that a single dose of cefuroxime provided insufficient spine tissue concentrations for spine procedures lasting more than 2–3 hours. Due to the fact that postoperative pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates, we aimed to evaluate if a twofold increase of standard dosage of 1.5g cefuroxime given as one double dose or two single doses with 4-hours intervals will lead to sufficient cefuroxime spine tissue concentrations throughout the dosing interval. Method. This is preliminary data for 8 out of 16 female pigs. Data from all 16 pigs will be included for the conference. Eight pigs were randomized into two groups: Group A received one double dose of cefuroxime (3g) as a bolus, and Group B received two single doses of cefuroxime (2×1.5g) with 4-hours intervals. Measurements were obtained from plasma, subcutaneous tissue (SCT), vertebral cancellous bone and the intervertebral disc (IVD) for 8-hours thereafter. Microdialysis was applied for sampling in solid tissues. The cefuroxime concentrations were determined using ultra-high performance liquid chromatography. Results. The time with concentrations above the minimal inhibitory concentration (T>MIC) for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml, was superior in all compartments when administering cefuroxime as two single doses with 4-hours intervals. For the target MIC of 4 μg/ml, the mean T>MIC in all compartments ranged between 53–73% and 85–95% for Group A and B, respectively. For both groups the area under the concentration-curve (AUC) was higher for plasma compared to the remaining compartments, and the lowest AUCs were found in the vertebral cancellous bone and the IVD. There were no differences in AUC between the two groups. Furthermore, the maximal concentrations were lower for both vertebral cancellous bone and IVD compared to both SCT and plasma. When comparing the two groups, higher maximal concentrations were found in all compartments for Group A. Tissue penetration was incomplete and delayed for all compartments and comparable between the two groups. Conclusions. Despite comparable pharmacokinetic results between the two groups, Group B exhibited superior T>MIC in all compartments for the clinical breakpoint MIC for Staphylococcus aureus of 4 μg/ml. As such administration of cefuroxime as two single doses with 4-hours intervals provided sufficient cefuroxime spine tissue concentrations for a minimum of 85% of an 8-hour dosing interval, which may be acceptable for most spine procedures

Aim. Pyogenic spondylodiscitis is associated with prolonged antimicrobial therapy and high relapse rates. Nevertheless, tissue pharmacokinetic studies of relevant antimicrobials in both prophylactic and therapeutic situations are still sparse. Previous approaches based on bone biopsy and discectomy exhibit important methodological limitations. The objective of this study was therefore to assess the concentration of cefuroxime in intervertebral disc (IVD), vertebral body cancellous bone, subcutaneous adipose tissue (SCT) and plasma pharmacokinetics after single dose administration by use of microdialysis (MD) in a large animal model. Method. Ten female pigs were assigned to receive 1,500 mg of cefuroxime intravenously over 15 min. Measurements of cefuroxime were obtained from plasma, SCT, the vertebral cancellous bone and the IVD for 8 hours thereafter. MD was applied for sampling in solid tissues. The cefuroxime concentration in both the MD and plasma samples was determined using ultra-high performance liquid chromatography. Results. For both the IVD and the vertebral cancellous bone, the area under the concentration-curve from zero to the last measured value was significantly lower than that of free plasma. Tissue penetration of cefuroxime was incomplete for the IVD, whereas for vertebral cancellous bone and SCT it was not. Furthermore, the penetration of cefuroxime from plasma to IVD was delayed. Additionally, a noticeable prolonged elimination rate of cefuroxime in the IVD was found. The maximal concentration and the elimination of cefuroxime were reduced in IVD compared to both SCT and vertebral cancellous bone. Due to this delay in elimination of cefuroxime, the time with concentrations above the minimal inhibitory concentration (T>MIC) was significantly higher in IVD than in SCT, vertebral cancellous bone and free plasma for MICs up to 6 μg/ml. Conclusions. MD was successfully applied for serial assessment of the concentration of cefuroxime in the IVD and the vertebral cancellous bone. Penetration of cefuroxime from plasma to IVD was found to be incomplete and delayed, but due to a prolonged elimination, the best results regarding T>MIC was found in IVD

Aim. This study evaluated target tissue concentrations of double dose cefuroxime administered intravenously as either one 15 min infusion of 3,000 mg (Group 1) or two single 15 min infusions of 1,500 mg administered 4 h apart (Group 2). Method. Sixteen pigs were randomised into two groups of eight. Cortical and cancellous bone, synovial fluid of the knee joint and subcutaneous adipose tissue concentrations were measured based on sampling via microdialysis. Plasma samples were collected as a reference. Comparison of the groups was based on time with concentrations above relevant minimal inhibitory concentrations (fT>MIC) of 4 μg/mL. Results. The mean time fT>MIC (4 μg/mL) across compartments was longer for Group 2 (280–394 min) than for Group 1 (207–253 min) (p<0.01). Cortical bone showed a tendency towards longer fT>MIC (4 μg/mL) in Group 2 (280 min) than in Group 1 (207 min) (p=0.053). Within 50 min after administration, the mean concentration of 4 μg/mL was reached in all compartments for both groups. The mean concentrations decreased below 4 μg/mL after approximately 4 h (Group 1) and 3 h (Group 2) from initiation of administration (time zero). Conclusions. During an 8 h interval, double-dose cefuroxime administered as 2 × 1,500 mg with a 4 h interval provides longer time above MIC breakpoint for Staphylococcus aureus (4 μg/mL) than a single bolus of 3,000 mg cefuroxime. To maintain sufficient tissue concentrations during longer surgeries, re-administration of cefuroxime (1,500 mg) should be considered 3 h after the first administration

Aim. A reason for treatment failure, in cases of periprosthetic bone infections and osteomyelitis, may be incomplete or heterogeneous tissue distribution of antimicrobials to the affected bone. Decreased bioavailability has been demonstrated in healthy bones but never in pathological bone tissue. Therefore, the aim was to obtain pharmacokinetic parameters of cefuroxime in infected bone tissue by means of microdialysis in a porcine model of implant associated osteomyelitis. Method. An implant cavity of 4 mm in diameter was drilled 25 mm into the right tibial bone of ten pigs (30 kg/BW). Subsequently, a small steel implant (K-wire 2 × 2 mm) and 10. 4. CFU of Staphylococcus aureus was inserted and injected into the implant cavity. Five days after inoculation, two additional drill holes of 2 × 25 mm were drilled into the trabecular bone tissue adjacent to the implant cavity and into the left uninfected tibia. After intravenous administration of 1500 mg of cefuroxime, the concentration was measured in plasma and in the three tibial drill holes for 8 hours. All measurements were performed with microdialysis. Post mortem, the presence of bone infection was assessed by computed tomography (CT) scans and cultures of swabs. Results. Destruction of bone tissue was seen on CT scans around all implant cavities but not in the adjacent trabecular bone tissue of the right leg or in the left leg. All swabs from the implant cavity and 8/10 swabs from the adjacent trabecular tissue were positive for S. aureus. Conversely, all swabs from the left tibia were negative. The area under the concentration-time curves differed significantly, with the lowest found in the implant cavity (P<0.001). Although not significant, cefuroxime penetration into the adjacent bone tissue was incomplete. Conclusions. This is the first study to show, by microdialysis, that the destructive bone processes associated with implant associated osteomyelitis significantly impair cefuroxime penetration. Our results support the clinical conception of fast diagnosis and initiation of antibiotic treatment if surgery is to be avoided. It is of crucial importance to know the exact level of antibiotics, which actually reaches a pathological bone focus in order to obtain more targeted and effective antibiotic treatments of bone infections

Current perception is that standard Cefuroxime only [C4] based prophylaxis regimen demonstrated higher association with C Difficile (C. Diff) diarrhoea. This has prompted change in antibiotics prophylaxis combination regimens like Flucloxacillin-Gentamycin (F-G], Teicoplanin- Gentamycin [T-G] and single dose Cefuroxime-Gentamycin [C-G]. The current study was done to investigate the association of C. Diff diarrhoea and surgical site infection (SSI) rate with Cefuroxime only regimen prophylaxis in fracture neck of femur surgery. A retrospective analysis for 2009–2012 was performed for 1502 neck of femur fracture patients undergoing surgery. The factors studied were ASA grade, SSI, C. Diff diarrhoea rates in patients with Cefuroxime (induction plus two doses) based prophylactic regimen. The data was obtained from coding department and further streamlined based on microbiology. 1242 patients were included in the study who received Cefuroxime only regimen. The Male : Female distribution was 353 : 889. The average ASA grade was 3. The analysis demonstrated that C. Diff diarrhoea rate in the study population was 1.29%. The SSI rate stood at 3.06% with superficial infection at 2.5 % and deep at 0.56 %. Our single centre based study demonstrated low C. Difficile related diarrhoea rates with Cefuroxime only regimen. The SSI rates were also low as compared to the current literature thus concluding that Cefuroxime only antibiotic regimen can safely be administered in neck of femur surgery

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

Aim. The current antibiotic treatment of periprosthetic joint infection (PJI) is optimized by measuring concentrations in plasma. However, it remains unclear whether effective concentrations of the antibiotics are reached at the site of PJI. Nonetheless, adequate target site concentrations are important to achieve effective eradication of the micro-organism. In order to determine the efficacy of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue in relation to the minimal inhibitory concentration (MIC) of the pathogen causing the PJI, we perform a pharmacokinetic/pharmacodynamic (PK/PD) study. Therefore, we aimed to develop validated analytical methods for analysis of cefuroxime and flucloxacillin in synovial fluid, synovial tissue and bone tissue. Method. Blank samples of synovial fluid, synovial tissue and bone tissue were obtained by orthopedic surgeons during surgery. For validation the samples of each matrix were spiked with both cefuroxime and flucloxacillin. Synovial tissue and bone tissue was pulverized with a mikro-dismembrator. Samples were kept frozen at −20°C until analysis. After a sample preparation quantification of cefuroxime and flucloxacillin in each matrix was performed on the ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). Stable-isotope-labeled meropenem-d6 served as internal standard. The linearity, limits of quantification, accuracy and precision and carry-over were determined for all methods separately. The methods were validated according to the European Medicine Agency (EMA) and Food and Drug Administration (FDA) guidelines on bioanalytical method validation. Results. These methods were successfully validated for cefuroxime and flucloxacillin quantification in all matrices according to the EMA and FDA guidelines. The limits of quantification were adequate to cover potential cefuroxime and flucloxacillin concentration in synovial fluid, synovial tissue and bone tissue as described in literature, with a range of 1–100mg/L for synovial fluid and 1–20 µg/g for synovial tissue and bone tissue (r >0.995). Accuracy and within-run precision were validated according to acceptance values (RSD <15%). Carry over was less than 20%. Matrix effects and recovery were investigated for synovial fluid. The results were within the range of 80–120%. Conclusions. The results of the validation fall within the limits of quantification according to the EMA and FDA guidelines. Therefore, these methods can be applied during a PK/PD study to discover the exposure of antibiotics in synovial fluid, synovial tissue and bone tissue at the site of infection in patients with a PJI

Aim. Tourniquet is widely used in extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios. Method. Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration. Results. Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 µg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 µg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08). Conclusions. Administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release

Background. We switched our antibiotic prophylaxis for elective hip and knee surgery from cefuroxime to flucloxacillin with single dose gentamicin in order to reduce the incidence of C. Diff diarrhoea. More patients subsequently appeared to develop acute kidney injury (AKI). Methods. During a twelve month period we examined the incidence of AKI sequentially in 198 patients undergoing elective hip or knee surgery: cefuroxime (n = 48); high dose flucloxacillin (median 8g) (n = 52); low dose flucloxacillin (median 4g) (n = 46); and cefuroxime again (n = 52). Results. There were no statistically significant differences between the four groups by chi-square tests for age, gender, nature of operation (hip or knee surgery), American Society of Anaesthesia (ASA) grade, mode of anaesthesia (spinal ± general anaesthetic v GA), baseline serum creatinine, pre-operative co-morbidity (hypertension, diabetes), pre-operative medication (NSAIDs, ACEI/ARBs or betablockers) and post-operative hypotension. Patients receiving high dose flucloxacillin required more vasopressors during surgery (p = 0.02 by Kruskal-Wallis test). The proportion of patients in each antibiotic group with any form of AKI by RIFLE criteria was: first cefuroxime group (8%), high dose flucloxacillin (52%), low dose flucloxacillin (22%), second cefuroxime (14%) (p < 0.0001). Odds ratios (OR) for AKI derived from a multivariate logistic regression model and arbitrarily assigning an OR of 1 to first cefuroxime group, were: high dose flucloxacillin 14.5 (95% CI, 4.2–49.7); low dose flucloxacillin 3.0(0.8–10.8); cefuroxime again 2.0(0.5–7.7). Three patients required temporary haemodialysis. Biopsies in two of these showed acute tubulo-interstitial nephritis. All three patients belonged to the high dose flucloxacillin group. None of the patients developed C Diff diarrhoea. Summary. We have shown a strong association between high dose flucloxacillin with single dose gentamicin prophylaxis and subsequent development of AKI which was not confounded by any of the co-variates we measured

Introduction. Acute renal dysfunction (ARD) following orthopaedic surgery is known to increase morbidity, mortality, and length of hospital stay. The aim of this study was to compare the incidence of new acute post-operative renal dysfunction between two cohorts of elective orthopaedic surgical patients receiving either cefuroxime or a combination of gentamicin and flucloxacillin as prophylactic antibiotic regimes. The study was initiated following a change in antibiotic prophylaxis within our unit from cefuroxime to gentamicin and flucloxacillin. Method. Using a standardised data collection tool we retrospectively reviewed medical records of 238 patients who had received 1.5g of cefuroxime (TKR: n = 128; THR: n=110). This data was compared to prospectively collected data from 254 patients (TKR=117 THR=137) who had received Flucloxacillin 2g and Gentamicin (with the dose based on height). Primary outcome measure for the study was the RIFLE criteria which grades renal impairment: 0-Nil, 1-Risk, 2-Injury, 3-Renal failure. Results. In a cohort of 238 patients who underwent arthroplasty and were administered cefuroxime, there were 4 patients (1.68%) who developed renal impairment. All 4 patients were grade 1 RIFLE (Risk) and all resolved by day 3 post-op. Of the 254 patients who received the new antibiotic regime of Flucloxacillin and Gentamicin, 24 (9.45%) had new onset renal impairment. 12 were RIFLE grade 1 (Risk), 7 RIFLE Grade 2 (Injury) and 5 were Grade 3 (Renal Failure) (p=0.0001, Fishers exact test). 7 of these patients remained in acute renal impairment between day 5 and day 7 post-op. Discussion. Patients who received the combination of Flucloxacillin and Gentamicin had a significant increased risk of renal impairment which was also likely to be more severe and last longer. Following analysis of this study we have now reverted back to Cefuroxime for antibiotic prophylaxis

In September 2011 our departmental protocol for peri-operative prophylactic antibiotic administration was altered from cefuroxime to gentamicin/flucloxacillin, in response to reported links between cephalosporin use and Clostridium difficile (C. diff) infection. As both gentamicin and flucloxacillin are known to be nephrotoxic in some patients, we investigated whether the new regimen increases the risk of Acute Kidney Injury (AKI) in patients undergoing elective and trauma hip and knee surgery, classified by severity (AKI Network criteria). The incidence of C. diff was noted. 10 out of 202 (5%) patients receiving cefuroxime (group A) developed AKI, compared with 23 of 210 (11%) patients receiving gentamicin and flucloxacillin (group B) (p=0.012). The severity of the renal injury was higher in the group B patients with 16 sustaining stage II/III AKI, whereas in Group A only one patient sustained a stage II injury and none stage III. The increased AKI rate in group B was observed equally in hip fracture patients and elective hip/knee replacement patients. However, 3 of 80 (4%) patients with hip fractures who received doses of cefuroxime developed C. diff, with none in the other groups (p=0.04). The choice of prophylactic antibiotics depends on a careful assessment of benefits and risks. Our data suggests that whereas hip fracture patients may have benefitted from the protocol change with reduced C. diff incidence, elective hip and knee replacement patients sustained additional harm. Different antibiotic regimens may be appropriate for these two groups

Treatment of open fractures is complex and controversial. The purpose of the present study is to add evidence to the management of open tibial fractures, where tissue loss necessitates cover with a free flap. We identified factors that increase the risk of complications. We questioned whether early flap coverage improved the clinical outcome and whether we could improve our antibiotic treatment of open fractures. From 2002 to 2013 we treated 56 patients with an open tibial fracture covered with a free flap. We reviewed patient records and databases for type of trauma, smoking, time to tissue cover, infection, amputations, flap loss and union of fracture. We identified factors thatincrease the risk of complications. We analyzed the organisms cultured from open fractures to propose the optimal antibiotic prophylaxis. Follow-up was minimum one year. Primary outcome was infection, bacterial sensitivity pattern, amputation, flap failure and union of the fracture. When soft tissue cover was delayed beyond 7 days, infection rate increased from 27% to 60% (p<0.04). High-energy trauma patients had a higher risk of amputation, infection, flap failure and non-union. Smokers had a higher risk of non-union and flap failure. The bacteria found were often resistant to Cefuroxime, aminoglycosides or amoxicillin, but sensitive to Vancomycin or Meropenem. Flap cover within one week is essential to avoid infection. High-energy trauma and smoking are important predictors of complications. We suggest antibiotic prophylaxis with Vancomycin and Meropenem until the wound is covered in these complex injuries. The authors wish to thank Christian E Forrestal for secretarial assistance, spreadsheets and figures, MD Maria Petersen for academic feedback and typography. Table: Culture results. Depicts the organisms isolated from the wounds, their number N and the number of bacteria that were fully susceptible to antibiotics according to the culture results in falling order on day 2–30 from the trauma. Most organisms were resistant to Cefuroxime. A blank space denotes that the organism was not tested against this antibiotic. A “0” denotes that the organism was not fully sensitive to the antibiotic

Salmonella osteomyelitis occurs infrequently in children without a sickle cell disease, and its subacute form is rare. Diagnosis is often delayed because its slow onset, intermittent pain and it can be confused with bone tumors. An otherwise healthy 13-year-old boy was admitted from another center in order to discard bone tumor in proximal tibia, with compatible radiologic findings. There was no history of trauma or previous illness. Twenty days ago, he had flu symptoms and myalgia. On the physical examination the child was feverless, showed increased heat over his left knee, considerable effusion and painful restriction of movement. Inflammatory laboratory results revealed erythrocyte sedimentation rate 46mm/h and C-Reactive protein, 11,2 mg/L. Radiographs revealed a lytic lesion localized in the proximal metaphysis and epiphysis. The MRI showed an area of edema around the lytic lesion and surrounding soft tissues. Images supported the diagnosis of subacute osteomyelitis, (Brodie abscess). Empirically, intravenous cefuroxime was started. Forty-eight hours post admission, the patient underwent abscess surgical debridement, washout and cavity curettage. Samples were sent for cytology, culture and sensitivity and acid fast bacilli culture and sensitivity. Collection´s count cell was 173.000/ L white cells. Collection´s culture revealed Salmonella B sensitive to ciprofloxacin. Stool culture did not yield any growth. Intravenous cefuroxime was administered during 10 days. The patient responded well as evidenced by clinical and laboratory improvement He was discharged with his left leg immobilized in a cast during 1 month and treatment was completed with oral ciprofloxacin 500mg /12 h during 2 months. The patient had full range of knee motion after 2 months. Last reviewed, after two years of the income, he was completed recovered, and the radiograph showed bone healing without physeal neither damage nor limb leg discrepancy. The most effective therapy of a confirmed salmonella osteomyelitis is a combination of radical operative intervention and targeted intravenous antibiotics as in our case. Faced with a subacute osteomyelitis, we have to remember that it may mimic bone tumors. We highlight the isolation of Salmonella B in a patient without sickle cell disease

Total joint arthroplasty (TJA) is one of the most successful procedures in orthopaedics. Despite the excellent clinical and functional results, periprosthetic joint infection (PJI) following TJA is a feared complication. For instance, the reported PJI rate after primary total knee arthroplasty is about 0.5–1.9%. In general, prevention of periprosthetic joint and surgical site infections is of utmost importance. This can be reduced by strict antisepsis, adequate sterilization of the surgical instruments and meticulous surgical technique. An indisputable role in prevention of SSI in TJA has been the use of peri-operative systemic antibiotic prophylaxis. The most common recommended antibiotics for prophylaxis in TJA are cefazolin or cefuroxime. In contrast, routine use of commercial antibiotic-loaded bone cement (ALBC) in primary total joint arthroplasty is still a concern of open debate. The use of antibiotic-loaded bone cement delivers a high concentration of antibiotics locally and can decrease the infection rate, which is supported by several studies in the literature. In this context, we present the pros of routine use of commercial antibiotic-loaded bone cement

Aim. Infection rates after management of open fractures are still high. Existing guidelines regarding prevention of this complication are inhomogeneous. A survey directed to orthopaedic trauma surgeons worldwide aims to give an overview of current practices in the management of open fractures. Method. An international group of trauma surgeons and infection specialists with experience in the field of musculoskeletal infections developed a questionnaire that was distributed via email to all AOTrauma members worldwide. Descriptive statistical analysis was performed. Results. 1197 orthopaedic trauma surgeons answered the survey (response rate: 4,9% of all opened emails). Cephalosporins are the most commonly used antibiotics for systemic prophylaxis in open fractures (cefazolin: 51,46% cefuroxime: 23,6%, ceftriaxone: 14,54%). In Gustilo type III open fractures gentamicin (49,12%) and metronidazole (33,58%) are often added. 86% (n=1033) reported to give the first dosage of systemic antibiotics in the emergency department as soon as the patient arrives. Only 3% (n=34) reported pre-hospital administration at the scene of the accident or during transport to the hospital. While most respondents administer antibiotics over 24h in type I open fractures (34%, n=405), for type II open fractures the most often mentioned duration is 72h (26%, n=306). For type III a 7 days course was most often performed (38%, n=448). Overall, there is a tendency to longer durations with increasing severity. However, a vast majority agreed that the optimal duration is not well defined in the literature (71%, n=849). 20psi,”Jet-Lavage”). The amount of irrigation fluid has a bimodal distribution with two peaks at 4–6 liters (24%, n=286) and at 8–10 liters (24%, n=282). Conclusions. Results from our survey give an overview of current practices and identify certain aspects in the management of open fractures where treatment protocols are very heterogenous and guidelines not well accepted. These controversies demand for further research in this field to provide better evidence

Aim. Antibiotic prophylaxis is critical for the prevention of fracture related infection (FRI) in trauma patients, particularly those with open wounds. Administration of prophylactic antibiotics prior to arrival at the hospital (e.g. by paramedics) may reduce intraoperative bacterial load and has been recommended; however scientific evidence for pre-hospital administration is scarce. Methods. The contaminated rabbit humeral osteotomy model of Arens was modified to resemble the sequence of events in open fractures. In an initial surgery representing the “accident”, a 2mm mid-diaphyseal hole was created in the humerus and the wound was contaminated with a clinical Staphylococcus aureus strain (mean 1.6×106 Colony Forming Units, CFU). The animals were allowed recover for 4 hours mimicking the period from trauma to debridement. At this time, a second procedure was performed in order to debride and irrigate the wound, and to fix a complete osteotomy that was made through the initial defect. Three test groups were included (n=8 rabbits per group): 1) no antibiotic therapy; 2) standard “in-hospital” antibiotic prophylaxis (24 hours therapy starting 30 minutes before surgery); 3) “pre-hospital” antibiotics (single dose 15 minutes after the “accident”). The antibiotic used was cefuroxime and was administered in a weight-adjusted dosage. Results. In the absence of any antibiotic administration (group 1), high bacterial counts were identified at fixation (1.89×106 CFU) and at euthanasia (day 7, 7.70×107 CFU) in all rabbits. When 24 hours of antibiotics were administered commencing “in hospital” (group 2), the bacterial load during fixation surgery was slightly reduced (CFU 9.88×105) and 50% of animals were infected at euthanasia. When one single shot of antibiotics was administered in the “pre-hospital” setting (group 3), the bacterial load during fixation surgery was significantly lower than for both groups 1 and 2(CFU 2.34×103) yet all animals were infected at euthanasia. Conclusions. Early pre-hospital administration of antibiotics significantly reduced the bacterial load in the operative field at the time of debridement compared to regular prophylaxis. However, continuation of systemic antibiotics is necessary in order to prevent infection in this model

In 2011 health policy dictated a reduction in iatrogenic infections, such as Clostridium difficile (C. diff), this resulted in local change to antimicrobial policy in orthopaedic surgery. Previous antimicrobial policy was Cefuroxime, this was changed to Flucloxacillin and Gentimicin. Following this change an increased number of patients appeared to suffer from acute kidney injury (AKI). We initially evaluated the incidence of AKI pre and post antibiotic change and found a correlation between the Flucloxacillin and AKI. We then made changes to antibiotic policy to mitigate the increased rates of AKI and proceeded to evaluate the outcomes. In this prospective study all patients admitted with fracture neck of femurs were identified from the National Hip Fracture database and data obtained. The degree of AKI was classified according to the validated RIFILE criteria. Evaluation showed a 4 fold decrease, from 13% to only 3%, in AKI after introduction of the modified antibiotic policy. C.difficile continues to be non-existent since this change. Flucloxacillin obviously had a significant impact on this patient group. However, we have shown that with appropriate changes to antibiotic policy AKI associated morbidity can be significantly reduced. Dose dependent antibiotics will now be given based on weight and eGFR

In late 2011 there was a change in antimicrobial policy in orthopaedic surgery to reduce the Clostridium difficile (C. diff) rate, this was inducted top down from government, to PCT, to hospital trust. The previous antimicrobial policy was Cefuroxime, this was changed to Flucloxacillin and Gentimicin. Following this change it was noticed an increased number of patients appeared to suffer from acute kidney injury (AKI). This led us to evaluate the incidence of AKI pre and post antibiotic change and look at the causes behind this. In this retrospective study all patients admitted with fracture neck of femurs were identified from the National Hip Fracture database and data pulled. The degree of AKI was classified according to the validated RIFILE criteria. Evaluation showed 2–4 fold increase in AKI since antibiotic change. Although mortality was decreased in these patients, the incidence of AKI had increased significantly. However, C. difficile has been obliterated by this change. The investigation highlights potential problems with increased rates of AKI amongst NOF patients, since antibiotic change. Flucloxacillin may have significant impact on this patient group. Dose dependent antibiotics will now be given based on weight and eGFR. Further analysis of this new change needs to be evaluated