Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Aims. Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up. Methods. A retrospective review of 1,060 patients who underwent TKA between May 2016 to July 2020 was performed. There were 572 patients in the IV group and 488 in the IO group, with minimal 30 days of follow-up. Patients were followed up at regularly scheduled intervals (two, six, and 12 weeks). No differences between groups for age, sex, BMI, or baseline comorbidities existed. The IV group received an IV dose of 15 mg/kg vancomycin given over an hour preceding skin incision. The IO group received a 500 mg dose of vancomycin mixed in 150 ml of normal saline, injected into proximal tibia after tourniquet inflation, before skin incision. All patients received an additional dose of first generation cephalosporin. Evaluation included preoperative and postoperative serum creatinine values, tourniquet time, and adverse reactions attributable to vancomycin. Results. Incidence of PJI with minimum 90-day follow-up was 1.4% (eight knees) in the IV group and 0.22% (one knee) in IO group (p = 0.047). This preliminary report demonstrated an reduction in the incidence of infection in TKA using IO vancomycin combined with a first-generation cephalosporin. While the study suffers from limitations of a retrospective, multi-surgeon investigation, early findings are encouraging. Conclusion. IO delivery of vancomycin after tourniquet inflation is a safe and effective alternative to IV administration, eliminating the logistical challenges of timely dosing. Cite this article: Bone Joint J 2021;103-B(6 Supple A):13–17

Aims. The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Introduction. Vancomycin is a commonly used antibiotic for prophylaxis in total joint replacement surgery. Several studies have reported superior local tissue concentration of vancomycin using intraosseous (IO) infusion compared with standard intravenous (IV) administration in total knee arthroplasty (TKA). We reviewed patients undergoing primary TKA who received IO vancomycin to a group receiving IV vancomycin. Methods. A retrospective review of 1038 patient who underwent primary TKA at our institution was performed from May 1, 2016 to May 1, 2019. This was a consecutive series of patients before and after we adopted this technique. IO vancomycin administration technique has been previously reported from our institution (500mg vancomycin in 200mL solution). Comparisons included preoperative and postoperative creatinine values, adverse reaction to vancomycin, tourniquet time, re-operation rates, periprosthetic joint infection rate at 1 year. Results. There were 482 patients in IO vancomycin group and 572 patients in IV vancomycin group. No differences between groups were present for patient age, sex, or BMI. No differences in creatinine values or tourniquet time were present and there were no adverse reactions to vancomycin in either group. Eight periprosthetic joint infections (1.4%) were reported in the IV group, and 1 (0.2%) periprosthetic joint infection was reported in the IO group at 1 year follow up, and this was statistically significant (p = 0.04, Fishers exact test). The overall reoperation rate was 1.7% (10 patients) in the IV group and 1.1% (5 patients), however, this was not statistically significant (p = 0.4371). The additional reoperations were for retained suture or small areas of poor superficial wound healing and were considered minor. Conclusion. Our study demonstrated that IO vancomycin in primary TKA reduced periprosthetic joint infection and is a safe and effective alternative to IV administration. Furthermore, IO infusion also eliminates the logistical challenges of timely prophylactic antibiotic administration before TKA

Introduction. Vancomycin is a prophylactic antibiotic used to protect against methicillin resistant staph aureus. Recent literature has suggested that using intraosseus (IO) infusions are capable of providing improved local tissue concentrations compared to intravenous (IV) access. The purpose of this study is to evaluate clinical outcomes of patients who received pre-operative IO vancomycin for total knee arthroplasty (TKA). Methods. Patients who received IO vancomycin (500mg vancomycin in 200ml NS) as standard of care from September 1, 2018 to March 1, 2019 were retrospectively evaluated. This data was compared to primary and revision TKAs performed immediately prior to the initiation of IO administration. Evaluation included pre and post-op creatinine values, tourniquet time (TT), and knee-related 30 and 90-day complications. Data for primary and revision TKA cases were analyzed independently. Results. Final analysis had 100 primaries and 29 revisions in the control (IV) and 100 primaries and 19 revisions in the intervention (IO) arm. 30 and 90-day complications were not significantly different in primaries, while decreased 30–day complications for revisions approached significance (control=17.2%, intervention=10.5%). 90-day complications were decreased in the revision group receiving IO (Control=27.6%, Intervention = 0%; p=0.015). No cases of Redman Syndrome were identified. No increase in post-operative creatinine values occurred. TT was increased by 1.87min in the PI, which was not statistically significant (p=0.10). Discussion / Conclusion. We've demonstrated IO vancomycin is a safe and effective alternative to using pre-operative IV vancomycin. This is one of the largest series to date evaluating the clinical outcomes while using IO antibiotics pre-operatively in TKA. Patients who receive IO vancomycin have equivalent or improved 30 and 90-day complication rates, significantly so in revision TKAs. In addition, this study evaluated longer-term outcomes of revision TKAs that are provided IO vancomycin, proving it may be appropriate to extend indications. For figures, tables, or references, please contact authors directly

Introduction. Intraosseous administration of low dose vancomycin has been proven to produce 6 to 20 times higher tissue concentrations compared to intravenous administration in both primary and revision knee replacement. However, these superior levels are achieved when the antibiotic given intraosseously is administered distal to a tourniquet that is inflated for the majority of the case. With increasing interest in limited, or no, tourniquet use during TKA we sought to study the tissue concentrations achieved with limited tourniquet use and intraosseously administered vancomycin compared to weight-based, time optimized intravenous administration. Methods. Twenty-four patients undergoing primary TKA were randomized to two groups. The Intravenous (IV) Group received weight based (15mg/kg) vancomycin timed to finish before incision. The Intraosseous (IO) Group received 500 mg of vancomycin injected as a bolus through a needle into the proximal tibia distal to an inflated tourniquet prior to skin incision. In the IO group, the tourniquet was deflated 10 minutes following the injection and re-inflated only for cementation. In the IV group, the tourniquet was only inflated for cementation. During the procedure, fat and bone samples were taken at regular intervals. Tissue antibiotic concentrations were measured using a validated technique involving high performance liquid chromatography. Results. Mean tissue concentrations of vancomycin in fat and bone samples from all time points were 3–10 times greater in the IO group (all results, p<0.01). At closure, mean vancomycin levels in fat were 6.0ug/g in the IV group vs 40.5ug/g in the IO group (p<0.001). Final bone levels were 8.3ug/g in the IV group vs 26.9ug/g in the IO group (p=0.009). Conclusion. In total knee replacement, IO administration of prophylactic vancomycin achieves significantly higher tissue concentrations versus IV administration given under ideal conditions despite limited tourniquet use. For figures, tables, or references, please contact authors directly

Aims. The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown. Methods. A review of all revision TKAs which were undertaken between 2006 and 2018 in a tertiary referral centre was performed, including all those meeting the consensus criteria for PJI, in which organisms were identified. Using a cluster analysis, three chronological time periods were created. We then evaluated the antibiotic resistance of the identified bacteria between these three clusters and the effectiveness of our antibiotic regime. Results. We identified 129 PJIs with 161 culture identified bacteria in 97 patients. Coagulase-negative staphylococci (CNS) were identified in 46.6% cultures, followed by Staphylococcus aureus in 19.8%. The overall resistance to antibiotics did not increase significantly during the study period (p = 0.454). However, CNS resistance to teicoplanin (p < 0.001), fosfomycin (p = 0.016), and tetracycline (p = 0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and was the most effective agent. Conclusion. Although we were unable to show an overall increase in antibiotic resistance in organisms that cause PJI after TKA during the study period, this was not true for CNS. It is concerning that resistance of CNS to new antibiotics, but not vancomycin, has increased in a little more than a decade. Our findings suggest that referral centres should continuously monitor their bacteriological analyses, as these have significant implications for prophylactic treatment in both primary arthroplasty and revision arthroplasty for PJI. Cite this article: Bone Joint J 2021;103-B(6 Supple A):171–176

Aims. The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an in vitro medium environment against methicillin-sensitive Staphylococcus aureus (MSSA). Materials and Methods. Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon’s test. Results. MSSA was inhibited for 12 days by the tantalum cylinders and for nine days by the cement cylinders. At day one, the mean zone of inhibition was 28.6 mm for the tantalum and 19.8 mm for the cement group (p < 0.001). At day ten, the mean zone of inhibition was 3.8 mm for the tantalum and 0 mm for the cement group (p < 0.001). The porous tantalum cylinders soaked only with phosphate buffered solution showed no zone of inhibition. Conclusion. Compared with cement, tantalum could release antibiotics for longer. Further studies should assess the advantages of using antibiotic-loaded porous tantalum implants at revision arthroplasty. Cite this article: Bone Joint J 2019;101-B:848–851

Aims. Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP. Methods. This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI. Results. In all, 10,484 knees (90.8%) received cefazolin, while 1,066 knees (9.2%) received a non-cephalosporin agent (either vancomycin or clindamycin) as preoperative prophylaxis. The rate of PJI in the cefazolin group (0.5%; 48/10,484) was significantly lower than the rate of PJI in the non-cephalosporin group (1.0%; 11/1,066) (p = 0.012). After controlling for confounding variables, the odds ratio (OR) of developing a PJI was increased in the non-cephalosporin cohort compared to the cefazolin cohort (OR 2.389; 1.2 to 4.6); p = 0.01). Conclusion. Despite the use of topical irrigant solutions and addition of local antimicrobial agents, the use of a non-cephalosporin perioperative antibiotic continues to be associated with a greater risk of TKA PJI compared to cefazolin. Strategies that increase the proportion of patients receiving cefazolin rather than non-cephalosporin alternatives must be emphasized. Cite this article: Bone Jt Open 2022;3(1):35–41

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190

Aims. The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups. Methods. A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm. 3. cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate. Results. For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion. These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162

Introduction. Periprosthetic infection (PJI) after primary total knee arthroplasty (TKA) remains a challenging issue affecting 1–2% of cases. Locally delivered prophylactic antibiotics, including tobramycin or gentamicin mixed in polymethylmethacrylate (PMMA) bone cement and vancomycin powder, are increasingly used despite a lack of high quality evidence for either practice. In this study, we report the antibiotic susceptibility of organisms recovered in culture from patients with acute prosthetic joint infection after primary TKA to gentamicin, tobramycin and vancomycin. Methods. Using a retrospective database of all primary TKA performed at a single institution between January, 1 2014 and July 1, 2018, we identified 18 cases of acute PJI after primary TKA, as defined by the Musculoskeletal Infection Society 2011 guidelines as less than 3 months from symptoms or index surgery to presentation. The use of antibiotic bone cement during the index procedure and time to surgical management of the infection were recorded. Fluid cultures and tissue cultures were obtained intraoperatively at the time of revision. The organisms from positive cultures underwent MIC testing to gentamicin, tobramycin and vancomycin using a gradient diffusion method (ETEST). MIC breakpoints for susceptibility were based on Clinical and Laboratory Standards Institute definitions. Results. 18 cases of PJI after TKA were identified, including 4 polymicrobial infections (22.2%) (Table 1). Average time to revision for infection was 38 days (range: 6–84 days). 34.8% of bacterial isolates were resistant to gentamicin, 39.1% were resistant to tobramycin and 17.4% were resistant to vancomycin. Of the 8 bacterial isolates resistant to gentamicin, 7 (87.5%) were susceptible tobramycin. Of the 9 bacterial isolates resistant to tobramycin, (88.9%) were susceptible to vancomycin. One bacterial isolate, a Fusobacterium nucleatum from a polymicrobial infection was resistant to gentamicin, tobramycin and vancomycin. Conclusion. Over one third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides pre-mixed in commercially available bone cements. All but one of the bacteria resistant to gentamicin and tobramycin were susceptible to vancomycin. The addition of vancomycin to bone cement or as powder in the surgical field has the potential to expand antibiotic coverage to include most organisms responsible for acute PJI after TKA. For figures, tables, or references, please contact authors directly

Introduction. Debridement, Antibiotics and Implant Retention (DAIR) remains the norm for the treatment of acute periprosthetic joint infection (PJI) despite less than optimal success rates. Intraosseous (IO) administration of vancomycin has been shown to have significantly increased local bone and tissue concentrations compared to systemic antibiotics, with lower systemic antibiotic levels compared to intravenous. The purpose of this study was to evaluate if the addition of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective review of 35 PJI TKA patients who underwent DAIR combined with IO vancomycin (500mg) was performed with minimum 12-month follow-up. 26 patients were treated for acute perioperative or acute hematogenous infections following primary TKA. Nine were treated for chronic infections with components that were considered unresectable (ie) constructs with ingrown cones, sleeves, or long cemented stems in elderly comorbid patients. Primary outcome was defined by no reoperations for infection nor clinical signs or symptoms of PJI. Results. The average follow up for acute infection was 16.5 months (range 12.1–24.2) and 15.8 months (range 12–24.8) for chronic infections with unresectable components. Overall eradication rates for acute infection was 93.1% while only 44.4% for chronic infections with unresectable components. MSIS host grade was a significant indicator of failure (p<0.001). Conclusion. The use of IO vancomycin at the time of DAIR yielded improved results compared to standard irrigation and debridement in acute periprosthetic infections. Its use in chronic infections should remain cautious. While these results are encouraging, this technique requires longer follow-up before widespread adoption

Two-stage revision surgery for infected total knee replacement offers the highest rate of success for the elimination of infection. The use of articulating antibiotic-laden cement spacers during the first stage to eradicate infection also allows protection of the soft tissues against excessive scarring and stiffness. We have investigated the effect of cyclical loading of cement spacers on the elution of antibiotics. Femoral and tibial spacers containing vancomycin at a constant concentration and tobramycin of varying concentrations were studied in vitro. The specimens were immersed and loaded cyclically to 250 N, with a flexion excursion of 45°, for 35 000 cycles. The buffered solution was sampled at set intervals and the antibiotic concentration was established so that the elution could be calculated. Unloaded samples were used as a control group for statistical comparison. The elution of tobramycin increased proportionately with its concentration in cement and was significantly higher at all sampling times from five minutes to 1680 minutes in loaded components compared with the control group (p = 0.021 and p = 0.003, respectively). A similar trend was observed with elution of vancomycin, but this failed to reach statistical significance at five, 1320 and 1560 minutes (p = 0.0508, p = 0.067 and p = 0.347, respectively). However, cyclically loaded and control components showed an increased elution of vancomycin with increasing tobramycin concentration in the specimens, despite all components having the same vancomycin concentration. The concentration of tobramycin influences both tobramycin and vancomycin elution from bone cement. Cyclical loading of the cement spacers enhanced the elution of vancomycin and tobramycin

Introduction. First generation cephalosporins remain the gold standard perioperative antibiotic for total hip and knee arthroplasty (THA, TKA). However, some patients have documented or self-reported allergies to antibiotics, most commonly penicillin, that result in changes to perioperative antibiotic coverage. Furthermore, patients testing positive for methicillin resistant staphylococcus aureus (MRSA) represent another group where an alternative to cefazolin, typically vancomycin, is often chosen for perioperative prophylaxis. The aims of this study were to 1) characterize the antibiotic choices for perioperative prophylaxis at the time of primary TKA and THA, 2) assess the efficacy of a preoperative antibiotic allergy testing program, and 3) determine rates of periprosthetic joint infection (PJI) based on perioperative antibiotic regimen. Methods. We evaluated all patients undergoing primary TKA or THA at a single academic institution from January 2004-May 2017, yielding a cohort of 29,695 patients. A series of institutional databases were combined to determine which patients underwent antibiotic allergy testing prior to surgery, outcomes from the allergy consultation, perioperative antibiotic management strategy, and survivorship free of infection until final follow-up. Results. Antibiotic allergy testing was performed in 3,411 patients (11.5%) on the basis of a patient provided history of possible penicillin or cephalosporin allergy. Among those tested, 3,310 patients (97.0%) were cleared by the allergist to use cephalosporins in the perioperative period and 2,883 patients (87.1%) eventually received cefazolin. For the entire cohort, 28,174 patients (94.9%) received an operative antibiotic regimen including cefazolin and 1,521 patients (5.1%) received non-cefazolin antibiotics, most commonly vancomycin or clindamycin. Survivorship free of PJI was significantly higher among patients receiving cefazolin compared to non-cefazolin antibiotics with the most rapid divergence occurring within 2 months of surgery (p<0.001) (Figure 1). Survivorship free of PJI in the cefazolin compared to the non-cefazolin groups was 99.40% vs 99.34% at 1 month, 99.11% vs 98.55% at 2 months, 98.83% vs 98.22% at 1 year, and 98.15% vs 96.96% at 10 years (Table 1). Notably, the increased PJI rate observed in the non-cefazolin group was not attributable to high preoperative MRSA prevalence as 0 of the 38 PJIs grew MRSA on culture. The number needed to treat with cefazolin to prevent 1 PJI was 164 patients at 1-year and 84 patients at 10-years. Therefore, potentially 6,098 PJIs could be prevented by 1-year and 11,905 by 10-years in a cohort of 1,000,000 primary TKA and THA patients. Conclusions. This study demonstrates a significantly higher rate of PJI when non-cefazolin antibiotics are used for prophylaxis during primary TKA and THA, which is likely attributable to the superior spectrum of coverage for common PJI organisms compared to vancomycin or clindamycin. This is supported by the increased rate of non-MRSA PJI observed in the non-cefazolin cohort. Furthermore, cefazolin has been shown to act synergistically with vancomycin against MRSA. This work highlights the positive impact of a formal preoperative antibiotic allergy testing program to increase cefazolin usage. Also, surgeons may consider using cefazolin as a dual agent in the case of known MRSA colonization, whenever possible for PJI prophylaxis during TKA and THA. For any figures or tables, please contact authors directly

Introduction. Periprosthetic joint infection (PJI) remains the main cause of failure in primary and revision total knee arthroplasties (TKAs). Local delivery of antibiotics, mainly antibiotic-loaded bone cement (ALBC), is commonly employed to prevent PJI. Over the past decade, tantalum and porous titanium have been successfully utilized as metaphyseal fixation devices to address bone loss and improve biologic fixation during revision TKA. However, no study has examined the antimicrobial properties compared to bone cement. The purpose of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement (ALBC) and smooth titanium alloy (STA) to inhibit Staphylococci bacterial agents in an in vitro medium environment, based on the evaluation of the zone of inhibition (ZOI) and the antibacterial activity duration. Our study hypothesis was that we will found no significant difference between groups to inhibit Methicillin-Sensitive or Methicillin-Resistant Staphylococcus aureus (MSSA/MRSA) agents. Methods. Thirty beads made of 3 different materials (tantalum/ 3D porous titanium/ STA) were bathed during 1hour inside of a solution made of 1g vancomycin with 20-mL of sterile water for injection (bath concentration: 50 mg/mL). Ten 1cm. 3. cylinders were also created mixing standard surgical cement with 1g of Vancomycin in standardized sterile molds (ALBC beads). Finally, thirty beads made of tantalum/ 3D porous titanium/ STA were bathed in phosphate buffered saline solution to act as a control group. Cylinders were then placed on agar plates inoculated with MSSA and MRSA. Inhibition zone diameters were measured each day and cylinders were transferred onto a new inoculated plate. Inhibition zones were measured with a manual Vernier caliper and with automated software. The mean inhibition zones between groups were compared using the Wilcoxon Test. Results. The inter-class coefficient correlation values indicated an optimal intra-observer and inter-observer reproducibility for ZOI measurement (ICC 0.96 and ICC 0.98). For MSSA and MRSA, no inhibitory effect was found in the control group and antibiotic-loaded STA beads exhibited a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads exhibited larger inhibition zones than cement beads (all p<0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After 6 days, ALBC presented larger inhibition zone than the 3D porous titanium, but no difference was found with tantalum. For MRSA, both tantalum and 3D porous titanium beads had significantly larger inhibition zones than ALBC each day until day 6 for tantalum (all p<0.01) and until day 3 for 3D porous titanium (all p<0.04). ALBC presented larger inhibition zone than tantalum and 3D porous titanium from day 7 to 9 (all p<0.04). Conclusion. Our results demonstrate that porous metal implants can deliver local antibiotics over slightly varying time frames based on our in vitro analysis. Antibiotic-impregnated tantalum and 3D porous titanium constructs exhibited superior antimicrobial properties when compared to STA. Future goals include impregnating porous metals with antibiotics for intraoperative use during revision TKA. For figures, tables, or references, please contact authors directly

Introduction. Management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a challenging task. Antibiotic management remains elusive due to differences in epidemiology and resistance between countries and reports. Increasing resistance of bacteria is a concern. The aim of this study was to investigate the development of antibiotic resistance of main causative bacteria in a single center. Methods. A retrospective review of all revision TKA between 2006 and 2018 in a tertiary referral center was performed. Included were cases meeting the consensus criteria for PJI with at least two positive cultures. Three chronological groups were created using a two-step cluster analysis. Results. In 129 cases of PJI there were 161 different bacteria identified by growth in culture. Of all bacteria 76.4% were gram positive, 23.6% were gram negative. Coagulase-negative Staphylococci (CNS) were diagnosed in 46.6% cultures, followed by Staphylococcus aureus in 19.8% of cultures. Overall antibiotic resistance (p=0.454) and Staphylococcus aureus resistance (p=0.788) have not increased during the study period. CNS resistance to teicoplanin (4% to 44%; p<0.001), fosfomycin (16% to 44%, p=0.016) and tetracycline (0% to 28%, p=0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and remained the most effective agent. Conclusion. The increasing resistance to several antibiotics over a little more than a decade is concerning. This study suggests that referral centres should continuously monitor obtained cultures as this has significant implications for both prophylactic treatment in primary as well as empirical antibiotic treatment in PJI. Resistance profiles may differ between centres and are subject to dynamic changes

Introduction. Our objective is to describe early and midterm results with the use of a new knee prosthesis as an articulating spacer in planned two-stage management for infected total knee arthroplasty. As a second objective, we compared outcomes between the group with a retained first stage and those with a completed 2-stage revision. Methods. Forty-seven patients (48 knees) from January 2012 and November 2017 underwent a 2-stage exchange with an articulating spacer with new implants was used for a chronic knee periprosthetic joint infection with a mean follow-up of 3.7 years (2–6.5 years). The most frequently identified infecting organism was MSSA (31%), MRSA (21%) or MRSE (20%). At the first stage, a new PS femoral component and a new all-polyethylene posterior stabilized (PS) tibial component or a standard PS tibial liner were cemented with antibiotic-cement, typically 3.6 gm tobramycin and vancomycin 1.5 gm. IV antibiotics for six weeks were administered. The planned reimplantation was at 3 months, but ninetteen spacers (14 all poly tibias and 5 tibial liner) were retained for over 12 months. Postoperative assessment included knee range of motion (ROM), quality of life (QOL) scores (SF-12, WOMAC, KOOS, Oxford, and UCLA scores), and a satisfaction scale from 0–100%. Results. Of the 48 knees, 8 failed due to lack of infection control, and 2 died within the first year for medical reasons (4%), giving a failure rate of 17% (8/46). One of these knees was not revised due to poor medical status. Of the remaining 7, 2 had a repeat 2-stage exchange, one a single stage revision and 4 irrigation and debridement with retained implants. All 7 had a successful outcome with infection control after this, leaving a permanent failure rate of 2% (1/46). Five of the 19 knees with initially retained implants were revised to a second stage after 12 months for continued pain or instability (1/14 all poly tibia and 4/5 PS liner). There were no significant differences in final range of motion or QOL scores between patients with a retained first stage procedure and those who underwent a second stage operation. Also, there was no statistically significant difference in the initial failure rate due to infection between patients with a complete 2-stage revision and those with a retained first stage (19% (6/31) vs. 14% (2/14), respectively; p=0.613). Conclusions. When an all poly tibial implant is used a spacer in two-stage exchange arthroplasty, it may be retained for over 12 months, with no difference in infection control, range of motion, and quality of life assessment to patients with complete 2-stage revision surgery. With this technique, the second stage may be delayed in patients who are doing well, and may never need to be revised, hence we propose the new term “one-and-a-half stage exchange”

Aims

Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy.

Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be successfully delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices in to clinical use. One approach is to follow a stepwise strategy, with the first step of seeking clearance for a temporary UHMWPE spacer containing gentamicin sulfate. In this study, we explored the effect of gentamicin sulfate (GS) content in UHMWPE on GS elution rate and antimicrobial activity against methicillin-sensitive S. aureus(MSSA). We also assessed the effect of spacer fabrication on the activity of gentamicin sulfate. We prepared and consolidated UHMWPE/GS blends in varying concentrations. After consolidation, we fabricated test samples with surface area (350mm2) to volume (300mm3) ratio of 1.2 for elution in 1.5ml phosphate buffered saline at body temperature for up to six months and quantified eluted GS content using liquid chromatography – mass spectrometry (LCMS). We assessed the antibacterial activity of the obtained samples in vitro against various concentrations of MSSA (103–106 CFU/ml). Furthermore, we quantified the probability of bacterial colonization of UHMWPE impregnated with GS compared to GS containing bone cement. We assessed any detectable changes in activity of eluted GS caused by spacer fabrication by screening m/z peaks of GS isomers in mass spectra obtained from LC-MS. Gentamicin sulfate activity was not compromised by the elevated temperature and pressure used during spacer fabrication. Elution rate of GS increased with increasing GS content in the blends studied. At comparable elution rates, the GS-loaded UHMWPE was either equivalent or better in terms of antibacterial and anticolonization properties when compared with gentamicin containing bone cement. GS-impregnated UHMWPE is a promising material for temporary spacers