Aim. Local antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine. With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ. Method. The bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation. The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate. Results. The mean concentration of CFZ in the eluate obtained from BC type A incubated for 2h was higher compared to BC type B, respectively 581 mg/l and 297 mg/l. However, the elution profile is the same for both types: the CFZ concentration in the eluates drops within the first 24h from 581 mg/l to 365 mg/l (37%) for BC type A and from 297 mg/l to 132 mg/l (56%) for BC type B. After 24h no further significant CFZ release is seen. Impregnation of the bone chips before or after gamma irradiation did not affect this elution profile. Conclusions. Bone chips treated with scCO2 show a comparable elution pattern compared to non-scCO2 treated bone chips. AB release depends on the properties of the AB, making it impossible to copy the same impregnation protocol for different antibiotics. The stability of CFZ in solution at 37°C and its release are a major concern when establishing an impregnation protocol with CFZ

Aim. Allograft bone chips used in complex bone reconstruction procedures are associated with an increased infection risk. The perioperative use of systemic cefazolin is standard to prevent infection, but is less effective in the presence of avascular bone grafts. Bone chips have been described as a carrier for local delivery of antibiotics, but impregnation with cefazolin in a prophylactic setting has not been described. We aimed to obtain a prolonged cefazolin release from bone chips to maximize the prophylactic effect. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were incubated for 20 min- 4h under atmospheric pressure or under vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Without hydrogel, cefazolin release was limited to 4 hours. When vacuum was applied during impregnation, elution of cefazolin exceeding the MIC (minimal inhibitory concentration) from decellularized lyophilized bone chips was obtained for 36 hours. Use of a collagen hydrogel and vacuum treatment resulted in a high concentration at 24 hours, but did not support prolonged release for any of the three types of tested bone chips. In contrast, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 μg/ml, declining to the MIC at 72 hours, while no longer measurable after 92 hours. Such elution profile is desirable, since high initial levels are important to maximize antibacterial action whereas the complete wash out prevents antibiotic resistance. By increasing the cefazolin concentration during impregnation, elution above the MIC could be obtained for 120 hours. Impregnated bone chips stored at −20° C for 3 months performed similarly to freshly impregnated bone chips. Conclusions. Bone chips processed with the described hydrogel-based impregnation protocol allows tunable delivery of cefazolin for a local prophylactic effect

Aim. To prevent infections after orthopaedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics and may provide the necessary local antibiotic levels for prophylaxis. To be efficient a prolonged release is required. In contrast to vancomycin with proven efficient prolonged release from Osteomycin, this has not been described for cefazolin. We developed a protocol to bind cefazolin to bone chips by means of a hydrogel composed of proteins naturally present in the human body. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analysed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Conclusions. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile seems desirable, with high initial levels to maximize anti-bacterial action and low levels for a limited time to stimulate osteogenesis. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Aim. Periprosthetic joint infection (PJI) is a severe complication after total joint arthroplasty. To prevent PJI, strict infection prevention measures are followed in combination with surgical antibiotic prophylaxis (SAP). To date, scientific reports concerning the optimal duration of SAP in revision arthroplasty are scarce. The aim of this multicenter open-label, randomized controlled trial in the Netherlands, is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip and knee. Method. Included patients with an assumed aseptic hip or knee revision procedure received a single dose of 2 or 3 gram cefazolin preoperatively. Patients were randomly assigned in a 1:1 ratio to receive extended prophylaxis of cefazolin during 5 days postoperatively versus no prophylaxis after wound closure. Patients were excluded if evidence of PJI at revision. The primary endpoint was the incidence of PJI within one year after revision arthroplasty. PJI was defined according to the 2018 Philadelphia consensus criteria. With a sample size of 746 patients, an alpha of 5% and a power of 80%, superiority of the extended regimen would be shown if the lower boundary of the 95% confidence interval (CI) of the absolute between-group difference of the percentage of PJI is below −4%. Results. In total 751 patients were included for analysis: 379 in the single dose cefazolin group and 372 in the extended group. Within one year, PJI occurred in 2.6% (10/379) in the single dose group and 2.4% (9/372) in the extended group (risk difference, −0.2 percentage points; 95% CI, −2.5 to 2.0%), thus superiority was not shown. Adverse drug events were seen in 20 cases with extended and 7 cases with a single dose prophylaxis. Conclusions. Extended prophylaxis is not significantly superior to a single dose of cefazolin to prevent PJI within the first year after revision arthroplasty of the hip or knee. This is the first randomized controlled trail in which the duration of SAP in the selected group of patients undergoing revision arthroplasty was studied. Extending SAP after closure of the wound could increase the selection or induction of antimicrobial resistance, has an increased risk for adverse drug events, and is therefore not in line with the primary goal of antimicrobial stewardship, comprising optimizing clinical outcomes and ensuring cost-effective therapy while minimizing unintended consequences of antimicrobial use

Aim. To provide proof of concept in an in vivo animal model for the prevention of prosthetic joint infection prevention using electric fields along with conventional antibiotic prophylaxis. Corresponding Author: Marti Bernaus. Method. First, we standardized the animal model to simulate implant contamination during the surgical procedure. We then implanted cobalt-chrome prostheses adapted to both knees of two New Zealand White rabbits, under standard aseptic measures and antibiotic prophylaxis with cefazolin. Prior to implantation, we immersed the prostheses in a 0.3 McFarland inoculum of S. aureus (ATCC 25923) for 30 seconds. In the first animal (control), the joint was directly closed after washing with saline. In the second animal (case), both prostheses were treated with electric current pulses for 30 seconds, washed with saline, and the joint was closed. After 72 hours, both animals were reoperated for the collection of periprosthetic tissue and bone samples, and prosthesis removal. In all samples, we performed quantitative cultures prior to vortexing and sonication, as well as prolonged cultures of the sonication broth. We confirmed the absence of contamination by identification with MALDI-TOF (VITEK-MS) and automated antibiotic susceptibility testing of the isolated colonies (VITEK-2). Results. In the “control” animal, we isolated S. aureus in all studied samples. The bacterial count expressed as log10 (cfu/cm2) in the prostheses of the right and left legs was 9.38 and 8.86, respectively. The bacterial count expressed as log10 (cfu/mL) in bone and periprosthetic tissue biopsies was 2.70 and 2.72 in the right leg and 3.24 and 3.87 in the left leg, respectively. In the “case” animal, where an electric field was applied to the implant after placement in addition to cefazolin prophylaxis, all samples (prosthesis, bone, and periprosthetic tissue) were negative, and no isolation of the inoculated strain of S. aureus was obtained after incubation of the sonication broth for 14 days. Conclusions. This in vivo model suggests the potential effectiveness of applying an electric field to a prosthetic implant in combination with cefazolin for the prevention of PJI development, after exposure of the implant to an inoculum of S. aureus (ATCC 25923). Our findings need to be confirmed using a larger sample size

Aim. In 10% of the presumed aseptic hip or knee revisions, a low-grade infection is unexpectedly diagnosed based on the tissue samples taken during revision. Extended antimicrobial prophylaxis can possibly reduce the failure rate in cases of unexpected PJI, because the prophylaxis can be considered as early empiric treatment. In this randomized controlled study we analysed whether extended antimicrobial prophylaxis compared to a single dose is beneficial to improve the outcome of treatment in unexpected PJI in revision arthroplasty. Method. This study was nested in a randomized clinical trial comparing single-dose cefazolin with prolonged prophylaxis (15 doses of cefazolin over 5 days) for revision arthroplasty of the hip or knee. For this analysis, patients were included if an unsuspected PJI (defined as ≥2 positive intraoperative tissue samples with the same microorganism) was diagnosed. PJI treatment consisted of 12 weeks of a rifampicin-based regimen in Staphylococcal PJI, without removal of the prosthesis. We examined Infection characteristics and success of treatment after one year, defined as the absence of signs or treatment for PJI during follow-up. Results. After randomization of 662 patients, 68 unexpected PJI were diagnosed. In 5 cases no antimicrobial treatment was started. The success rate after one year follow-up for those who received PJI treatment was 96% (28/29) in the single dose group and 91% (31/34) in the extended prophylaxis group (p=1.00). The most frequently identified pathogens in unexpected PJI were Cutibacterium acnes (n=50) and Staphylococcus epidermidis (n=14). The causatives were susceptible for the cefazolin prophylaxis in 61 of the 63 cases. The interval between the stopped prophylaxis and the re-start of antimicrobial treatment was on average 10 days (SD 4) for the single dose and 5 days (SD 4) for the extended group. The mean duration of antimicrobial treatment was 83 days (SD 12) and did not differ between both groups (p=0.16). Conclusions. This is the first randomized controlled trial in which extended prophylaxis showed no benefit on the prosthesis survival for patients with an unexpected PJI after assumed aseptic revision of the hip or knee prosthesis. The results imply that extended prophylaxis should not be given as part of early empiric therapy

Prosthetic joint infection (PJI) remains one of the most challenging complications to manage following total joint arthroplasty (TJA). There is a paucity of published data on the management of PJI in smaller, rural hospital settings. In this study, we investigate [1] the success rate of surgical management for PJI following TJA and [2] the microbiology of infecting organisms in this unique geographical environment. We performed a retrospective single-centre study at a rural hospital (Southland Hospital, Invercargill, New Zealand) over a 3-year period (2019 to 2022). All patients presenting with a first episode of PJI fulfilling Musculoskeletal Infection Society criteria after hip or knee arthroplasty were included. All patients had a minimum follow up of 6 months. Treatment success was defined eradication of infection. Twenty-one cases (14 hips and 7 knees) were identified. These were managed with Debridement, antibiotics, and implant retention (DAIR) procedure (n=14, 67%), single-stage revision (n=6, 29%), or long-term suppressive antibiotics (n=1, 4%). Of the DAIR patients, infection recurred in 50% and underwent subsequent revision. Of the single-stage revision patients, 17% failed and underwent subsequent revision. The overall success rate was 90%. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most isolated pathogen (57%,) with no methicillin-resistance Staphylococcus aureus (MRSA) identified. Overall, 90% of infecting organisms were cefazolin sensitive. These results suggest that management of PJI is a safe and viable treatment option when performed in a rural hospital setting, with comparable treatment success rates to urban centres. The incidence of MRSA is low in this setting. Rates of antibiotic resistance were relatively low and most organisms were sensitive to cefazolin, the routine antibiotic used in prophylaxis

Aim. Periprosthetic joint infection (PJI) is a feared complication of total joint arthroplasty of hip (THA) or knee (TKA). Debridement, antibiotic treatment, and implant retention (DAIR) is an effective treatment of early PJI. In the Netherlands, cefazolin resistance in early PJI after primary arthroplasty is low. Little is known about causative micro-organisms and resistance patterns in PJI after revision arthroplasty. No recommendations for empirical treatment are described in the current guidelines. The aim of this study is to describe the characteristics of PJI after revision arthroplasty and to evaluate whether the used empirical treatment regimens are adequate, based on microbiology data. Method. In this retrospective study we included patients with early PJI after aseptic revision of THA or TKA, treated with DAIR between 2012 and 2020. Success rate was defined as implant retention and no persistent or recurrent infection during one year follow-up. Results. We identified 96 patients with PJI. PJI was most frequently caused by Staphylococcus spp. (n=73), Gram-negative bacilli (n=31) or Enterococcus spp. (n=13). Polymicrobial infection was diagnosed in 38 PJIs. Mismatches were present in 72 (75%) of the PJIs (95% CI: 0.66–0.84). Table 1 shows the number of mismatches per empirical treatment regimen. Figure 1 shows the responsible micro-organisms for the mismatches. Success rate of PJI treatment was significant reduced for patients with mismatching compared to matching empirical therapy: 62% vs. 95% respectively (OR: 0.09, 95% CI: 0.01–0.68, p=0.004). If vancomycin would have been the empirical treatment, mismatches would have been reduced to 31 (32%) (95% CI: 0.23–0.42). With vancomycin-ciprofloxacin combination therapy the mismatches would have been reduced to 1% (95% CI: −0.01–0.03). Conclusions. There is a high number of mismatches in empirical treatment in early PJI after revision arthroplasty, which have significant influence on the outcome. Based on our data cefazolin should not be recommended as empirical treatment for this specific group. Our data shows that review of local data is necessary to improve treatment strategies, that eventually might improve outcome. Besides changing Gram-positive coverage, a prospective study is needed to assess the benefits of broader spectrum empiric antimicrobial treatment taken into account toxicity and other side effects such as antimicrobial resistance. For any tables or figures, please contact the authors directly

Aim. Following clean (class I, not contaminated) surgical procedures, the rate of surgical site infection (SSI) should be less than approximately 2%. However, an infection rate of 12.2% has been reported following removal of orthopedic implants used for treatment of fractures below the knee. The objective of this trial was to evaluate the effect of a single dose of preoperative antibiotic prophylaxis on the incidence of SSIs following removal of orthopedic implants used for treatment of fractures below the knee. Method. This multicenter, double-blind, randomized clinical trial included 500 patients from 19 hospitals with a follow-up of 6 months. Eligible were patients aged 18 to 75 years with previous surgical treatment for fractures below the knee who were undergoing removal of orthopedic implants. Exclusion criteria were an active infection or fistula, antibiotic treatment, reimplantation of osteosynthesis material in the same session, allergy for cephalosporins, known kidney disease, immunosuppressant use, or pregnancy. The intervention was a single preoperative intravenous dose of 1000 mg of cefazolin (cefazolin group, n = 228) or sodium chloride (0.9%; saline group, n = 242). Primary outcome was SSI within 30 days as measured by the criteria from the US Centers for Disease Control and Prevention. Secondary outcome measures were functional outcome, health-related quality of life, and patient satisfaction. Results. Among 477 randomized patients (mean age, 44 years [SD, 15]; women, 274 [57%]; median time from orthopedic implant placement, 11 months [interquartile range, 7–16]), 470 patients completed the study. Sixty-six patients developed an SSI (14.0%): 30 patients (13.2%) in the cefazolin group vs 36 in the saline group (14.9%) (absolute risk difference, −1.7 [95% CI, −8.0 to 4.6], P = .60). Conclusions. In patients undergoing surgery for removal of orthopedic implants used for treatment of fractures below the knee, a single preoperative dose of intravenous cefazolin compared with placebo did not reduce the risk of surgical site infection within 30 days following implant removal

Topically applied vancomycin powder has been used to decrease surgical site infection rates in spinal surgeries, however, randomized controlled trials in total joint arthroplasty are lacking. Application of vancomycin powder topically in the surgical site has theoretical benefit including high local concentration. In this study, we aimed to determine whether intra-operative topical antibiotics are safe and effective as IV antibiotics in preventing post-surgical site infections. The trial was a randomized controlled, double blind, non-inferiority study. All patients received pre-operative IV antibiotics (cefazolin or vancomycin) within 60 minutes of skin incision. The controlled group received two doses of post-operative IV antibiotics (two grams cefazolin or one gram vancomycin if cefazolin allergy). In the treatment group, the orthopaedic surgeon applied one gram vancomycin powder (500mg applied directly on the prosthesis and 500mg applied above the closed joint capsule). The incidence of acute surgical site infection was defined as positive deep cultures within 42 days of procedure. All patients with evidence of infection underwent joint aspiration for culture. After one year, 80 patients had received the topical vancomycin treatment and 85 patients had received the standard treatment. In the topical vancomycin group versus the controlled group, the average age was 64 vs 66, average BMI was 35.7 vs 33.4, number of males 33 vs 29, number of females 47 vs 56, and diabetic patients 16 vs 13. The number of infections in the topical vancomycin group was three vs zero in the post-operative IV antibiotic treatment group. One Tailed Z-test P Value = 0.03. This study statistically demonstrated inferiority of topical vancomycin in comparison to the use of IV antibiotics post-operatively in preventing deep wound infections in TKA. The authors would caution against the sole use of intra-operative vancomycin in TKA to prevent post-operative infection

Aim. The current recommendation in Norway is to use four doses of a first-generation cephalosporin (cefazolin or cephalotin) as systemic antibiotic prophylaxis (SAP) the day of surgery in primary joint arthroplasty. Due to shortage of supply, scientific development, changed courses of treatment and improved antibiotic stewardship, this recommendation has been disputed. We therefore wanted to assess if one dose of SAP was non-inferior to four doses in preventing periprosthetic joint infection (PJI) in primary joint arthroplasty. Method. We included patients with primary hip- and knee arthroplasties from the Norwegian Arthroplasty Register and the Norwegian Hip Fracture Register for the period 2005-2023. We included the most used SAPs (cephalotin, cefazolin, cefuroxime, cloxacillin and clindamycin), administered as the only SAP in 1-4 doses, starting preoperatively. Risk of revision (Hazard rate ratio; HRR) for PJI was estimated by Cox regression analyses with adjustment for sex, age, ASA class, duration of surgery, reason for- and type of arthroplasty, and year of primary arthroplasty. The outcome was 1-year reoperation or revision for PJI. Non-inferiority margins were calculated for 1, 2 and 3 doses versus reference of 4 doses of SAP at the day of surgery, against a predetermined limit of 15% increased risk of PJI. Results. In total 274,188 primary arthroplasties (total hip 133,985, hemi hip 51,442, and total knee 88,761) were included. Of these primary arthroplasties, 2,996 (1.1%) had subsequent revisions for PJI during the first postoperative year. One dose of SAP was given in 9,603 arthroplasties, two doses in 10,068, three doses in 18,351, and four doses in 236,166 arthroplasties. With the recommended four doses as reference, the HRR (95% CI) for 1-year revision for infection was 0.9 (0.7-1.1) for one dose, 1.0 (0.8-1.2) for two doses, and 0.9 (0.8-1.1) for three doses. The corresponding adjusted 1-year revision incidences for PJI was 0.9 (0.7-1.1), 1.0 (0.8-1.2), 0.9 (0. 8-1.1) and 1.0 (1.0-1.1) for one, two, three and four doses respectively, and less than four doses was found to be non-inferior. Conclusions. One preoperative dose of SAP in primary joint arthroplasty surgery seems to be non-inferior to the current recommendation of four doses of a first-generation cephalosporin as PJI-prophylaxis. This finding may simplify the course of treatment for arthroplasty patients, save costs, and improve antibiotic stewardship

Large cartilage lesions in younger patients can be treated by fresh osteochondral allograft transplantation, a surgical technique that relies on stable initial fixation and a minimum chondrocyte viability of 70% in the donor tissue to be successful. The Missouri Osteochondral Allograft Preservation System (MOPS) may extend the time when stored osteochondral tissues remain viable. This study aimed to provide an independent evaluation of MOPS storage by evaluating chondrocyte viability, chondrocyte metabolism, and the cartilage extracellular matrix using an ovine model. Femoral condyles from twelve female Arcott sheep (6 years, 70 ± 15 kg) were assigned to storage times of 0 (control), 14, 28, or 56 days. Sheep were assigned to standard of care [SOC, Lactated Ringer's solution, cefazolin (1 g/L), bacitracin (50,000 U/L), 4°C storage] or MOPS [proprietary media, 22-25°C storage]. Samples underwent weekly media changes. Chondrocyte viability was assessed using Calcein AM/Ethidium Homodimer and reported as percent live cells and viable cell density (VCD). Metabolism was evaluated with the Alamar blue assay and reported as Relative Fluorescent Units (RFU)/mg. Electromechanical properties were measured with the Arthro-BST, a device used to non-destructively compress cartilage and calculate a quantitative parameter (QP) that is inversely proportional to stiffness. Proteoglycan content was quantified using the dimethylmethylene blue assay of digested cartilage and distribution visualized by Safranin-O/Fast Green staining of histological sections. A two-way ANOVA and Tukey's post hoc were performed. Compared to controls, MOPS samples had fewer live cells (p=0.0002) and lower VCD (p=0.0004) after 56 days of storage, while SOC samples had fewer live cells (p=0.0004, 28 days; p=0.0002, 56 days) and lower VCD (p=0.0002, 28 days; p=0.0001, 56 days) after both 28 and 56 days (Table 1). At 14 days, the percentage of viable cells in SOC samples were statistically the same as controls but VCD was lower (p=0.0197). Cell metabolism in MOPS samples remained the same over the study duration but SOC had lower RFU/mg after 28 (p=0.0005) and 56 (p=0.0001) days in storage compared to controls. These data show that MOPS maintained viability up to 28 days yet metabolism was sustained for 56 days, suggesting that the conditions provided by MOPS storage allowed fewer cells to achieve the same metabolic levels as fresh cartilage. Electromechanical QP measurements revealed no differences between storage methods at any individual time point. QP data could not be used to interpret changes over time because a mix of medial and lateral condyles were used and they have intrinsically different properties. Proteoglycan content in MOPS samples remained the same over time but SOC was significantly lower after 56 days (p=0.0086) compared to controls. Safranin-O/Fast Green showed proteoglycan diminished gradually beginning at the articular surface and progressing towards bone in SOC samples, while MOPS maintained proteoglycan over the study duration (Figure 1). MOPS exhibited superior viability, metabolic activity and proteoglycan retention compared to SOC, but did not maintain viability for 56 days. Elucidating the effects of prolonged MOPS storage on cartilage properties supports efforts to increase the supply of fresh osteochondral allografts for clinical use. For any figures or tables, please contact the authors directly

Perioperative antibiotic prophylaxis remains one of the most important strategies for prevention of periprosthetic joint infection (PJI) with current guideline recommending a first or second generation cephalosporin. Penicillin (PCN) allergy is often reported by patients, which often results in avoidance of administration of cephalosporins due to fear of cross-reactivity. Alternative medications, such as vancomyin, are often used despite reduced antimicrobial coverage. The purpose of this study was to determine if PCN allergic patients who received vancomycin alone prior to elective primary total joint arthroplasty were at increased risk of developing a subsequent PJI. A retrospective review of 7,602 primary total joint arthroplasties (TJAs) performed between 2005 and 2013 in two institutions were identified using a prospective institutional database. Patient reported PCN or cephalosporin allergy was electronically queried from the anesthesia note. Patients who recieved multiple prophylactic antibiotics, or had unavailable perioperative antibiotic information, or those who received medication other than cefazolin and vancomycin were excluded. PJI was determined using a cross-match with an institutional PJI database constructed from International Classification of Diseases (ICD)-9 codes. Logistic regression analysis was then performed to evaluate the risk of subsequent PJI. The rate of PJI was 1.4% (32/2296) in patients with a reported PCN allergy that received vancomycin alone versus 1.1% (59/5306) in non-PCN allergic patients that received cefazolin alone. The multivariate analysis, with the given sample size, did not detect a statistically significant increased risk of PJI when vancomycin was administered alone (adjusted odds ratio: 1.23, 95% CI 0.6–3.1, p=0.35). While there was no significant differences in the organism profile between PJIs in both groups, the rate of PJI caused by resistant organisms was higher in patients who received vancomycin alone (11.9%, 7/59) compared to those who received cefazolin (3.1%, 1/32). While administration of perioperative prophylactic vancomycin alone during elective primary arthroplasty does not seem to result in a higher rate of subsequent PJI, patients who received vancomycin alone and developed a PJI were more likely to develop an infection with an antibiotic resistant organism. Future studies are needed to determine the most appropriate prophylactic antibiotic for patients who undergo elective arthroplasty and report PCN allergy

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

INTRODUCTION. Surgical site infections (SSI) in orthopaedics are a major source of postoperative morbidity. Although perioperative antibiotic prophylaxis is a common practice, orthopaedic infections are still high in numbers, due to the increasing use of osteosynthesis material and implants. Implants are avascular and can be easily colonized with biofilm-producing germs. For both, effective prophylaxis and treatment of orthopaedic infections, the right choice of the antibiotics used, the mode of application (only systemic or systemic & local), the timing, dosage and the duration of antibiotics are of extremely high importance. Their inappropriate use does not only lead to failures in prevention or treatment of infections, but may also promote microbial resistance development and may cause serious side effects for the patients. SELECTION & USE OF ANTIBIOTICS. Prophylaxis. Broad-spectrum prophylactic antibiotics should help to eliminate the germs before they start to colonize the implant. For prophylactic purposes the recently published AAOS guidelines [1] recommend the use of cephalosporins, such as cefazolin or cefuroxim, administered within one hour prior to surgery. In cases of suspected beta-lactam allergy, clindamycin or vancomycin can be used. The latter one is also recommended in cases of MRSA colonisation. Due to extended infusion times, vancomycin should be started within two hours prior to incision. In cases of blood loss or long op duration, antibiotic administration must be repeated (e.g. cefazolin, every 2–5 hrs; vancomycin, every 6–12 hrs). There is no evidence of a benefit of continued antibiotic administration past 24 hrs of end of surgery [2]. Treatment. In cases of established infections, use of antibiotics is only considered as an adjuvant to surgical debridement. Typically, the choice of the appropriate antibiotic depends on the bacteria, its antibiotic sensitivity profile and the health state of the patient. A combination of rifampicin & a quinolone (or rifampicin & vancomycin in cases of MRSA) for at least 2 wks up to several months has shown good results [3]. In chronic infections with biofilm involvement, all foreign material must be removed and locally delivered antibiotics via e.g. PMMA as carrier (spacers, PMMA-chains) are of additional clinical benefit. ROLE OF LOCAL ANTIBIOTICS. There is general consensus that PMMA chains or PMMA spacers loaded with specific antibiotics support the eradication of bone and joint infections, because of the high local concentrations achieved. The exact treatment time is, however, variable, ranging from few weeks up to several months. Only small amounts of these local antibiotics are systemically detectable and do not represent a major risk for side effects. Still a matter of debate is the benefit of antibiotic impregnated PMMA for infection prophylaxis. Although common practice in Europe, its routine use in e.g. primary arthroplasty is still discussed in other world regions. Meanwhile, evidence accumulates that joint infection rates are, indeed, lower, if antibiotic loaded bone cement with high initial release rates is routinely used in arthroplasty. 4.

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. Obese patients are not only more likely to receive total joint arthroplasty, but are also more prone to postoperative complications. The most severe complication is a prosthetic joint infection (PJI), occurring two to four times more often in severely obese patients (BMI ≥ 35kg/m. 2. ) compared to non-obese patients. This higher risk for PJI may be attributed to higher glucose levels in case of diabetes mellitus, diminished wound healing or inadequate antibiotic prophylaxis. To ultimately improve the prevention measures for this specific patient category, we aimed to describe the clinical and microbiological characteristics of early acute PJI in severely obese patients. Method. We retrospectively evaluated patients with early acute PJI of the hip and knee treated with DAIR between 2006 and 2016 in three Dutch hospitals. According to protocol, cefazolin was administered as antibiotic prophylaxis during arthroplasty and adjusted to bodyweight. PJI was diagnosed using the criteria described by the Musculoskeletal Infection Society. Early acute PJI was defined as less than 21 days of symptoms and a DAIR performed within 90 days after index surgery. Several clinical and microbiological variables were collected and analyzed. Severe obesity was defined as a BMI ≥ 35kg/m. 2. . Results. A total of 356 patients were analyzed, including 73 severely obese patients (20.5%). Compared to patients with a BMI < 35kg/m. 2. , severely obese patients were relatively young (69 years vs 74 years, p=0.001), female (75.3% vs 56.9%, p=0.005), with PJI of the knee (35.6% vs 20.8%, p=0.025) and arthroplasty indicated for osteoarthritis (87.7% vs 63.3%, p=0.001). They had higher incidences of diabetes mellitus (34.2% vs 18.7%, p=0.005) and hypertension (74.0% vs 59.0%, p=0.021). Severely obese patients had more often polymicrobial infections (67.4% vs 45.7%, p=0.009) and higher rates of infection with Enterococcus species (37.0% vs 15.8%, p=0.002) and Gram-negative rods, such as Proteus species (17.4% vs 2.3%, p<0.001). This finding was most prominent in hips, comprising Gram-negative PJIs in 32.6% of severely obese patients compared to 18.1% in non-severely obese patients (p=0.030). There were no differences in the number of infections due to Staphylococcus aureus or Staphylococcus epidermidis. Conclusions. Our results demonstrate that severely obese patients with early acute PJI have higher rates of polymicrobial infections with involvement of Gram-negative rods and enterococci, especially in the hip region. Our data stress the importance of improving preventive strategies in this specific patient category, which may entail extension of antibiotic prophylaxis to a broader Gram-negative and Gram-positive coverage

Aim. Surgical site infection (SSI) is associated with substantial morbidity, mortality and economic burden. Management of spinal SSI is becoming more challenging especially in instrumented cases, but is not well recognized as high risk procedure. The objective of this study was to determine the impact of procedure type comparing SSI risk with arthroplasties among all orthopaedic procedures. Method. Using prospectively collected data of consecutive samples in multi-center orthopedic SSI surveillance, we explored the differences in SSI rates within 30 days after surgery by procedure types. Patients who underwent surgery of single site between November 2013 and May 2016 were enrolled. SSI was our primary outcome. Urinary tract infection (UTI), and respiratory tract infection (RTI) were also evaluated. The definition of SSI was based on the CDC definition with slight modifications. All patients were followed for 30 days postoperatively. Multivariate logistic regression analyses were done, and variables were carefully selected for adjustments. Results. In total 8,907 single site surgeries were analyzed. There were four major procedure types, fracture repair 31%, arthroplasty 30%, spinal surgery without instrumentation 14.7% and spinal instrumentation surgery 13%. Patient backgrounds were male 41.4%, diabetes 13.5%, rheumatoid arthritis 3.8 %, present smoker 13.4%, mean BMI 23+4, and operative time 144+92 minutes. Cefazolin was administered in more than 98% of all cases, and were administered appropriately before surgery. SSI occurred in 102 cases (1.2%), and the SSI rates were 2.5% in spinal instrumentation surgery and 0.6% in arthroplasty. After adjustment with several clinically relevant variables such as age, sex, diabetes and ASA, spinal instrumentation surgery was the only procedure which remained significant with adjusted odds ratio (aOR) of 3.3 (1.8–6.2, P<0.01) compared with arthroplasties. The risk remained stable after adding further clinically relevant variables (aOR of 2.2 to 3.3). The risk was not significant for spinal surgery without instrumentation (aOR, 1.8; 0.9–3.5, P=0.10). Moreover, the risk of spinal instrumentation surgery was highest for UTI (aOR, 4.7; 2.9–7.6), P<0.01) and RTI (aOR, 3.7; 1.6–8.9), P<0.01) among all procedures. Conclusions. From our study, spinal instrumentation surgery was the only procedure to be significant after multivariate analysis, and the risk for SSI remained 2.2 to 3.3 fold higher compared with arthroplasties. The risk was also highest for several other major healthcare-associated infections. Considering the disastrous consequences, more interests and improvements in total perioperative care are needed for this procedure

Aim. Recent studies have indicated that the presence of P. acnes in the skin of the shoulder and around the acromion is higher than other body regions like the knee or the hip. The aim of this study was to estimate the presence of P. acnes in a real set of primary shoulder arthroplasty, after skin preparation with chlorhexidine and administration of empirical antibiotic therapy. Method. A prospective observational study involving 63 patients undergoing primary shoulder arthroplasty was designed. In all patients two skin biopsies with a 3 mm dermal punch and one subcutaneous tissue sample after surgical incision were obtained. Skin biopsies were obtained at the most anterior part of the surgical wound in case of superior approach and at the upper part in the deltopectoral approach. All patients underwent preoperative antibiotic prophylaxis with cefazolin 2g ev and skin preparation with 2% chlorhexidine alcoholic tinted before the start of surgery twice. The aerobic cultures were incubated at 37ºC for 7 days whereas the anaerobic ones incubated for 14 days. Results. A total of 63 consecutive patients who underwent shoulder arthroplasty (58 reverse shoulder arthroplasty and 5 anatomical) were analysed. 54 women and 9 men, mean age of 73.94 (SD 6.19). The indication for arthroplasty was a secondary arthropathy cuff injury in 42 cases, primary osteoarthritis in 3, acute fracture in 9 and fracture sequelae in 9. We obtained 189 tissue cultures (126 skin cultures and 63 subcutaneous) and 4 cultures were positive (2.02%) for P. acnes in 3 different patients. A first patient (female) had both positive skin cultures, the second patient (male) only had positive the subcutaneous tissue cultures and the third patient had positive also the subcutaneous tissue culture. The first patient underwent anatomical shoulder arthroplasty whereas the second and third patients underwent reverse shoulder arthroplasty. The time to grow was 15 days in first patient and 14 days in the second and third patient (mean 14.5 days). Conclusions. In a real setting of patients undergoing shoulder arthroplasty using antibiotic prophylaxis and standard preoperative skin preparation with chlorhexidine we found a low rate of positive cultures for P. acnes (2.02 %). The higher rate of P. acnes positive cultures in skin reported in previous studies may be caused by a different population study group (healthy and younger volunteers without antibiotic prophylaxis) or suboptimal culture technique (use of swaps)

Preoperative antibiotic prophylaxis remains one of the most important strategies for preventing periprosthetic joint infection (PJI). Current guidelines recommend giving universal antibiotic prophylaxis to all total joint arthroplasty (TJA) patients regardless of their medical conditions or immune status. The aims of this study were to determine if comorbidities influence the organism profile of PJIs and to investigate if the efficacy of the two most frequently used perioperative antibiotics (cefazolin or vancomycin) are affected by patient comorbidities. Using an institutional database, the influence of comorbidities on the organism profile of 1022 PJIs was evaluated. To investigate the influence of perioperative antibiotic monotherapy (cefazolin or vancomycin therapy) on PJI, 8575 primary TJAs were identified and analyzed based on their comorbidities. Patients with multiple perioperative antibiotics, prior septic arthritis, unavailable perioperative antibiotic information, or who underwent aseptic revision were excluded. PJI was determined from ICD-9 codes. While no comorbidities were associated with an increased rate of gram-positive or gram-negative infections, metastatic disease (odds ratio [OR] 7.54, p=0.006), rheumatologic disease (OR 1.63, p=0.046), and chronic pulmonary disease (OR 1.46, p=0.030) demonstrated an increased risk of Staphylococcus aureus PJI. In addition, metastatic disease (OR 5.71, 95% confidence interval [CI] 1.12–26.93, p=0.018), congestive heart failure (OR 2.2, 95% CI 1.16–4.00, p=0.010), chronic pulmonary disease (OR 1.76; 95% CI 1.09–2.78, p=0.015), and diabetes (OR 1.66; 95% CI 1.08–2.52, p=0.019) were associated with PJI from antibiotic resistant organisms. However, there was no difference in the rate of PJI between cefazolin and vancomycin monotherapy when stratified for the aforementioned comorbidities. The present study reveals that comorbidities do not significantly alter the organism profile of high-risk comorbidities and that comorbidities associated with immune deficits do not influence the rate of PJI between two different antibiotics. The results of this study thus support current guidelines, which provide a universal recommendation rather than a protocol that is tailored to a patient's preexisting comorbidities