Aim. One of the most severe complications of primary total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). Nowadays, the use of antibiotic-loaded cement for prevention of infection is still controversial. The aim of the present study is to evaluate the use of an antibiotic-loaded cement to reduce the infection rate in primary total knee arthroplasty. Method. Prospective randomized study, with 2893 cemented total knee arthroplasties performed between 2005 and 2010 in our institution. Two different groups were formed depending on which bone cement was used, without antibiotic (the control group) or loaded with erythromycin and colistin (the study group). All patients received the same systemic prophylactic antibiotics. The patients were followed for a minimum of twelve months. The rate of infection was analyzed according to the criteria of the Centers for Disease Control and Prevention (CDC). Results. In 1452 patients the prosthetic components were fixed using bone cement without antibiotic and in 1441 patients bone cement loaded with erythromycin and colistin was used. There were no differences between both groups in terms of demographic data (age, sex and BMI), either in operating time (p>0,05). The rate of infection was similar in both groups, being 2,0% (n=29) in the control group and 1,7% in the study group (p=0,58) at 8,7 years (SD 5,1) of follow up. In terms of prosthetic revision due to any cause (infected or aseptic), there wasn't differences between groups, performing a total of 61 revision arthroplasties in control group and 68 in study group (p>0,05). Moreover, we analyzed the erythromycin resistance rate, being no differences between both groups (p=0.6). Conclusions. The use of erythromycin and colistin-loaded bone cement in total knee arthroplasty did not lead to a decrease in the rate of infection when systemic prophylactic antibiotics were used, a finding that suggests that its use would not be indicated in the general population

Aim. Septic arthritis of the hip is a rare entity among the adult population, but with a potential severe repercussion. The most accepted treatment is the hip debridement, even though a notorious proportion of the cases need further hip replacement owing to the cartilage destruction. The aim of this study is to analyse all our cases of septic arthritis of the hip treated with a 2-stage strategy using an antibiotic-loaded cement spacer. Method. We present a retrospective review of all our cases of septic arthritis of the hip diagnosed between 2004 and 2016 that were treated with an antibiotic-loaded cement spacer. We analysed age, gender, comorbidities, aetiology, duration of symptoms, C-reactive protein values, erythrocyte sedimentation rate, initial treatment, cultures, definitive treatment and evolution. Results. A total of 14 cases were included with a mean age of 47 years: 8 men and 6 women. The aetiology of the arthritis was: haematogenous in 8 cases, after osteosynthesis in 5 cases and after arthroscopy in 1 case. An initial debridement was performed in 6 cases whereas the spacer was directly implanted in 8 cases. The cultures were positive for: Staphylococcus aureus (4 cases), Candida albicans (2 cases), Staphylococcus epidermidis (1 case), Pseudomonas aeruginosa (1 case), Enterococcus faecium (1 case), Serratia marcescens (1 case), Streptococcus dysgalactiae (1 case), Salmonella spp (1 case) and negative in 2 cases. The evolution was: total hip arthroplasty in 10 cases, spacer preserved in 2 cases, pending of hip replacement in 1 case and exitus in 1 case. All cases presented negative cultures at the moment of implantation of the definitive prosthesis. Conclusions. A 2-stage strategy using an antibiotic-loaded cement spacer prior to the definitive hip prosthesis is a good treatment for the septic arthritis of the hip in cases with important cartilage destruction

Aim. There is controversy regarding the use of Antibiotic-loaded cement (ALBC) as compared to non-antibiotic-loaded cement (NALBC) to reduce the overall infection rate without affecting implant survival or adding additional risks on fixation for primary total knee arthroplasty (TKA). Method. To conduct the analysis, we utilized the Catalan Arthroplasty Registry (RACat) for the TKAs implanted between 2005 and 2017. The primary variable recorded was the use of cement with or without antibiotics. Other recorded variables included were age, sex, diabetes mellitus, obesity, Charlson index and type of hospital. We analyzed the effect of ALBC vs. NALBC in reducing the risk of prosthetic infection at 3, 6, 12, and 24 months as well as prosthetic survival due to mechanical causes at 1, 5, and 10 years. Univariate and multivariable analyses of risk factors were conducted. Thereby, an interactive predictive model that determines the risk of prosthetic infection based on each patient's characteristics was created. Results. A total of 28,287 TKAs from the RACat were analyzed. In that total, there were 19,788 NALBC and 8,499 ALBC. The infection rates for TKAs with NALBC vs. those with ALBC at 3, 6, 12, and 24 months were respectively: 1.69% vs. 1.39% (p=0.132); 1.81% vs. 1.56% (p=0.147); 2.14% vs. 1.73% (p=0.030); 2.51% vs. 1.86% (p=0.001). A statistically significant reduction in periprosthetic infection rate was observed in the ALBC group at 12 and 24 months. No differences were observed between the two groups in terms of prosthetic mechanical survival. Being younger, male and having had previous knee surgery or having a high comorbidity index all led to a higher risk of prosthetic revision due to infection. Conclusions. The use of ALBC as a fixation method for TKA leads to a reduction in the risk of prosthetic infection without altering the mechanical survival of the implant. The creation of a predictive model helps determine the individualized risk of prosthetic infection based on the patient's characteristics

Aim. The preparation of antibiotic-containing polymethyl methacrylate (PMMA), as spacers generates a high polymerization heat, which may affect their antibiotic activity; it is desirable to use bone cement with a low polymerization heat. Calcium phosphate cement (CPC) does not generate heat on polymerization, and comparative elution testings are reported that vancomycin (VCM)-containing CPC (VCM-CPC) exceeded the antibiotic elution volume and period of PMMA (VCM-PMMA). Although CPC alone is a weak of mechanical property spacer, the double-layered, PMMA-covered CPC spacer has been created and clinically used in our hospital. In this study, we prepared the double-layered spacers: CPC covered with PMMA and we evaluated its elution concentration, antimicrobial activity and antibacterial capability. Method. We prepared spherical, double-layered, PMMA-coated (CPC+PMMA; 24 g CPC coated with 16 g PMMA and 2 g VCM) and PMMA alone (40 g PMMA with 2 g VCM) spacers (5 each). In order to facilitate VCM elution from the central CPC, we drilled multiple holes into the CPC from the spacer surface. Each spacer was immersed in phosphate buffer (1.5 mL/g of the spacer), and the solvent was changed daily. VCM concentrations were measured on days 1, 3, 7, 14, 28, 56, and 84. Antimicrobial activity against MRSA and MSSA was evaluated by the broth microdilution method. After measuring all the concentration, the spacers were compressed at 5 mm/min and the maximum compressive load up to destruction was measured. Results. The VCM concentration of the CPC+PMMA spacer exceeded that of the PMMA spacer at all-time points; in particular, it was approximately 7.3 times (109.30 vs. 15.03 μg/mL) and approximately 9.1 times (54.47 vs. 6.50 μg/mL) greater on days 14 and 28, respectively. Using the broth microdilution method, we found that the CPC+PMMA spacer had higher antimicrobial activity than the PMMA model. On day 56, the PMMA spacer lost the capability to inhibit bacterial growth, but the CPC+PMMA spacer maintained this ability. The average maximum compressive load for the CPC+PMMA was 7.28 kN, and that of PMMA was 16.21 kN. Conclusions. The CPC+PMMA spacer was superior to PMMA alone in VCM elution volume and duration, so CP- C+PMMA may be effective for the treatment of MRSA and MSSA infection. The double-layered, antibiotic-loaded cement spacer may maintain antibacterial capability and sufficient strength

Purpose. Failure resulting from a recurrent infection in total knee arthroplasty (TKA) is a challenging problem. Knee arthrodesis is one treatment option, however fusion is not always successful, as there is huge bone defect. The authors reports a new arthrodesis technique that uses a bundle of flexible intramedullary rods and an antibiotic-loaded cement spacer. Methods. There were 13 cases of arthrodesis due to recurrent periprosthetic joint infection, which were performed by the first author (WS Cho) at Asan Medical Center in Seoul from 2005 to 2014. All previous prosthetic components were removed and cement was thoroughly excised using a small osteotome. Two stage operation was done in most of cases. After thorough debridement, antibiotics loaded cement was inserted in first stage, flexible intramedullary rods were inserted retrogradely in the femoral side with the knee in flexion under fluoroscopy guidance. After filling the femoral intramedullary canal, the rods were then driven back securely into the tibial medullary canal. We aimed for as much rod length as possible to maximize stability. After 6 weeks of first stage operation, the rods of the femoral and tibial sides were arranged such that they overlapped and interdigitated to maximize mechanical strength, maintain the limb length and keep the rotational alignment. The interdigitating rod ends were tightly fixed using two (or three) cerclage wires. Antibiotic-loaded cement was filled into the knee joint space so that the cement is fit to the irregular contour of the femur and tibia, which was resulted from the severe bone loss. Postoperatively, patients were allowed to weight bear as tolerated. Results. The procedure was successful in every cases with no evidence of rod or cement failure at least 1 year follow up. Also there was no recurrence of infection. Conclusion. Although this simple method was not for bony union, the authors could achieve stable knee joint without recurrence of infection

Aim

Aim was to compare revision rates when using single versus dual antibiotic loaded cement (ABLC) in hip fracture arthroplasty and aseptic revision hip or knee arthroplasty using data from the Dutch national joint registry (LROI).

Aim. The aim of this investigation was to compare risk of infection in both cemented and cementless hemiarthroplasty (HA) as well as total hip arthroplasty (THA) following femoral neck fracture. Methods. Data collection was performed using the German Arthroplasty Registry (EPRD) In HA and THA following femoral neck fracture fixation method was divided into cemented and cementless protheses and paired according to age, sex, body mass index (BMI), and the Elixhauser score using Mahalanobis distance matching. Results. Overall in 13,612 cases of intracapsular femoral neck fracture, with 9,110 (66.9 %) HAs and 4502 (33.1 %) THAs were analyzed. Infection rate in HA was significantly reduced in cases with use of antibiotic-loaded cement compared to cementless fixated prosthesis (p=0.013). In patients with THA no statistical difference between cemented and cementless prothesis was registered, however after one year 2.4 % of infections were detected in cementless and 2.1 % in cemented THA. In the subpopulation of HA after one year 1.9 % of infections were registered in cemented and 2.8 % in cementless HA. BMI (p=0.001) and Elixhauser-Comorbidity-Score (p<0.003) were identified as risk factors of PJI, while in THA also cemented prosthesis demonstrated within the first 30 days an increased risk (HR=2.728; p=0.010). Conclusion. The rate of infection after intracapsular femoral neck fracture was significantly reduced in patients treated by antibiotic-loaded cemented hemiarthroplasty. In particular for patients with multiple risk factors for the development of a PJI the usage of antibiotic-loaded bone cement seems to be a reasonable procedure for prevention of infection

Infected total hip arthroplasty (THA) is catastrophic, but it is treatable with a high degree of success. Two-stage revision with an antibiotic-loaded cement spacer is the most widely accepted method of treatment, and considered by some to be the best method; however, single-stage treatment currently is used widely, and is gaining acceptance. Although antibiotic-loaded cement is considered to be important for antibiotic delivery after surgery, cementless revision is equally successful with one- or two-stage procedures. Delivery of antibiotics with depot methods, such as cement or bone graft impregnated with antibiotics, is considered to be effective, but the antibiotic levels rapidly deteriorate after the first three days, leaving the cement itself vulnerable to colonization by resistant organisms. Nephrotoxicity is not common, but it does occur, and necessitates removal of the cement. This can be catastrophic if the implants are fixed with antibiotic-impregnated cement. Success rates of THA revision for infection can be as high as 98%, but this rate is dependent on the organism. Failure rates of 20% are the norm for resistant organisms such as methicillin-resistant Staphylococcus aureus, The cost of this failure rate is huge. Failure probably is due to the low concentration of antibiotics in the operative site. Antibiotic infusion into the operative site achieves concentrations that are hundreds of times higher than can be achieved with any other technique and has the additional advantage of being able to be discontinued in the case of renal or auditory damage. Limited personal experience suggests that the failure rate of revision total hip with resistant organisms is significantly lower with intra-articular delivery than with other currently available methods. Between January 2002 and July 2013, 9 patients (9 hips) presented with late-onset acute infections in cementless THA with bone-ingrown implants. These patients were all more than 2 years from their original surgery and had acute symptoms of infection for 4 to 9 days. Two were the author's patients and 7 were referred from another institution. None had symptoms until the onset of their infection, and none had postoperative wound complications, fever, or prolonged pain suggestive of a chronic process. All were treated with debridement and head/liner exchange, followed by catheter infusion of intraarticular antibiotics. All remained free of signs of infection at a mean follow-up of 74 months (range, 62–121 months). This sequential series of successful treatment of late-onset infection of osteointegrated total hip replacement suggests that this is a highly effective method. It has the advantages of being a single-stage procedure, and of avoiding the catastrophic surgical procedure of removing fully osteointegrated total hip replacements

Infected total hip arthroplasty (THA) is catastrophic, but it is treatable with a high degree of success. Two-stage revision with antibiotic-loaded cement spacer is the most widely accepted method of treatment, and considered by some to be the best method; however, single-stage treatment currently is used widely, and is gaining acceptance. Although antibiotic-loaded cement is considered to be important for antibiotic delivery after surgery, cementless revision is equally successful with one- or two-stage procedures. Delivery of antibiotics with depot methods, such as cement or bone graft impregnated with antibiotics, is considered to be very effective, but the antibiotic levels rapidly deteriorate after the first three days, leaving the cement itself vulnerable to colonization by resistant organisms. Nephrotoxicity is not common, but it does occur, and necessitates removal of the cement. This can be catastrophic if the implants are fixed with antibiotic-impregnated cement. Success rates of THA revision for infection can be as high as 98%, but this rate is dependent on the organism. Failure rates of 20% are the norm for resistant organisms such as methicillin-resistant Staphylococcus aureus. The cost of this failure rate is huge. Failure probably is due to the low concentration of antibiotics in the operative site. Antibiotic infusion into the operative site achieves concentrations that are hundreds of times higher than can be achieved with any other technique and has the additional advantage of being able to be discontinued in the case of renal or otic damage. Limited personal experience suggests that the failure rate of revision total hip with resistant organisms is significantly lower with intra-articular delivery than with other currently available methods

Infected total hip arthroplasty (THA) is catastrophic, but it is treatable with a high degree of success. Two-stage revision with an antibiotic-loaded cement spacer is the most widely accepted method of treatment, and considered by some to be the best method; however, single-stage treatment currently is used widely, and is gaining acceptance. Although antibiotic-loaded cement is considered to be important for antibiotic delivery after surgery, cementless revision is equally successful with one- or two-stage procedures. Delivery of antibiotics with depot methods, such as cement or bone graft impregnated with antibiotics, is considered to be very effective, but the antibiotic levels rapidly deteriorate after the first three days, leaving the cement itself vulnerable to colonization by resistant organisms. Nephrotoxicity is not common, but it does occur, and necessitates removal of the cement. This can be catastrophic if the implants are fixed with antibiotic-impregnated cement. Success rates of THA revision for infection can be as high as 98%, but this rate is dependent on the organism. Failure rates of 20% are the norm for resistant organisms such as methicillin-resistant Staphylococcus aureus. The cost of this failure rate is huge. Failure probably is due to the low concentration of antibiotics in the operative site. Antibiotic infusion into the operative site achieves concentrations that are hundreds of times higher than can be achieved with any other technique, and has the additional advantage of being able to be discontinued in the case of renal or otic damage. Limited personal experience suggests that the failure rate of revision total hip with resistant organisms is significantly lower with intra-articular delivery than with other currently available methods

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalization, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intraarticular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included débridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 µg/mL. Mean serum vancomycin peak concentration was 6 ± 2 µg/mL and the mean serum vancomycin trough concentration was 3 ± 1 µg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 µg/mL and 20,167 µg/mL and trough concentrations were 724 µg/mL and 543 µg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean followup was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83 ± 9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; . sd . 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. For most patients, antibiotics alone are not an acceptable method of treatment, and surgery is necessary. The standard of care for established infection is two-stage revision with antibiotic-loaded cement during the interval period and parental antibiotic therapy for six weeks. Single-stage revision may have economic and functional advantages however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Our protocol has included single-stage revision using antibiotic-loaded cement in both THA and TKA. This was only undertaken when sensitive organisms were identified pre-operatively by aspiration and appropriate antibiotics were available to use in cement. Patients with immunocompromise, multiple infecting organisms or recurrent infection were excluded. Patients with extensive bone loss that required allograft reconstruction or where a cementless femoral component was necessary were also excluded. Our algorithm was validated first in the hip and extended to infected TKA in 2004. This protocol has now been applied in over 100 TKA revisions for infection between 2004 and 2009. Our single-stage revision rate is now over 25%. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two-stage revision cases. Whilst our indications are arbitrary and not based on specific biomarkers, we present excellent results for selective single-stage exchange. A minimum three-year follow up suggests that these patients have shorter hospital stays, higher satisfaction rates and better knee scores. An ongoing evaluation is in place. One-stage revision arthroplasty for infection offers potential clinical and economic advantages in selected patients

Aim. The risk for developing a periprosthetic joint infection (PJI) as a consequence of bacteremia is not clear, except for Staphylococcus aureus bacteremia, and patient-related risk factors for it are not known. The aim of this study was to investigate the risk for developing a PJI during any bacteremia and to find out possible risk factors leading to it. Method. All patients with a primary knee or hip joint replacement performed between September 2002 and December 2013 in a tertiary care hospital (n=14 378) were retrospectively followed up until December 2014. The mean follow-up time was 6.0 years (range 0–12 years). Positive blood culture results of the patients during the study period were obtained. PJIs during the study period were identified from several data sources. PJIs as a consequence of bacteremia were recorded and confirmed from patient records. Primary PJIs resulting in bacteremia were excluded. Binary logistic regression with univariate analysis was used to study potential risk factors for PJI among those with bacteremia. Results. Of the study patients, 542 (3.8%) had at least one episode of bacteremia. In total, there were 643 episodes of bacteremia. The incidence rate of bacteremia was 7.4 per 1 000 person-years. Seven percent (47/643) of the bacteremias resulted in a PJI. The risk for PJI was highest for bacteremias caused by Staphylococcus aureus (21% of bacteremias led to a PJI) and beta-hemolytic streptococci (21%), but it was low for gram-negative bacteria (1.3%). Patients with two or more bacteremias during the study period had an increased risk for developing a PJI (OR 2.29, 95%CI 1.17–4.50). Bacteremias occurring within a year from previous surgery were associated with the highest risk for developing a PJI. Chronic comorbidities, obesity, gender, joint location, indication for surgery or use of antibiotic-loaded cement did not affect the risk for PJI during bacteremia. Conclusions. The pathogen causing the bacteremia, number of bacteremias and the timing of bacteremia with respect to previous surgery affect the risk for developing a PJI as a consequence of bacteremia. Thus the type of pathogen, previous history of infections and the timing of bacteremia should be taken into account when evaluating the risk for PJI on a patient with bacteremia. On the other hand, significant patient-related risk factors for PJI during bacteremia could not be identified

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalisation, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intraarticular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included debridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 µg/mL. Mean serum vancomycin peak concentration was 6±2 µg/mL and the mean serum vancomycin trough concentration was 3±1 µg/mL at 2 weeks postoperative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 µg/mL and 20,167 µg/mL and trough concentrations were 724 µg/mL and 543µg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean followup was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83±9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months postoperatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimising systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

Periprosthetic joint infection (PJI) is one of the most feared complications following total knee arthroplasty (TKA). Despite improved peri-operative antibiotic management and local antibiotic-loaded bone cement PJI is reported in about 0.5–1.9 % of primary knee replacement. In case of revision knee arthroplasty the infection rate even occurs at about 8–10 %. Depending on an acute or late PJI several surgical methods are used to treat the infection. However, suffering of a late PJI, the only surgical procedure remains the exchange of the TKA in combination with a radical debridement and removal of all foreign material. In order to achieve complete debridement of the joint, the soft tissue must be radically excised. Frequently, the debridement of the posterior capsule causes severe difficulties, therefore it might be necessary to resect the collateral ligaments to be able to reach the posterior parts of the capsule. But this necessitates the use of a higher level of constraint such as a rotating or total hinge and fully cemented long stemmed revision implants. Furthermore, due to the cemented stems, a sufficient amount of antibiotic-loaded cement may be delivered to the bone as topical therapy. Up to now, several studies have shown excellent functional long-term results for hinge knee prostheses after PJI and a very good infection control rate. Advantages of the hinge knee prosthesis in cases of PJI are the opportunity for a complete debridement especially while addressing the posterior capsule after resection of the collateral ligaments and for delivering antibiotic-loaded bone cement at the stems of the prosthesis for topic therapy. Disadvantages are the need for a higher level of constraint and a possible higher blood loss due to the radical debridement

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalisation, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intra-articular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration. Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (trough levels of 8.4 and 4.2 μg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was determined to be 3.06 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included debridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 μg/mL. Mean serum vancomycin peak concentration was 6±2 μg/mL and the mean serum vancomycin trough concentration was 3±1 μg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 μg/mL and 20,167 μg/mL and trough concentrations were 724 μg/mL and 543μg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean follow-up was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83±9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimising systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

The infected joint arthroplasty continues to be a very challenging problem. Its management remains expensive, and places an increasing burden on health care systems. It also leads to a long and difficult course for the patient, and frequently a suboptimal functional outcome. The choice of a particular treatment program will be influenced by a number of factors. These include the acuteness or chronicity of the infection; the infecting organism(s), its antibiotic sensitivity profile and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon. Although there have been multiple developments to enhance our ability to effect two-stage techniques whilst limiting inpatient stay, cost and patient morbidity - these include functional spacers, the use of local as well as systemic antibiotics, and home intravenous therapy programmes – there is nevertheless still a considerable morbidity and mortality to the two-stage process, and a massive cost to the patient who has to have two operations with an unpredictable interval period in between and to the local tissues which have already been damaged and are violated on two occasions. The push for one-stage surgery has generally been from centers who are passionate about that technique and has involved a combination of knowing the organism in question prior to surgery, a very radical debridement, the use of hinge / tumor-type implants and prolonged antibiotic therapy post-surgery. The last decade has seen an evolution whereby we have recognised that treatment may be tailored to the patient. There is a big difference between a relatively healthy host and someone with multiple comorbidities, and a big difference between infection with a relatively benign organism and polymicrobial infection with multi-resistant bacteria or fungi. There has, therefore, been increased interest in the use of single-stage revision in order to decrease morbidity, potentially decrease mortality and to decrease cost to the health care system. Single stage revision may have economic and functional advantages, however. We have devised a protocol that dictates the type of revision to be undertaken based on host, organism and local factors. Whilst we believe that there is a role for both single- and two-stage techniques in our armamentarium, we have gradually evolved to increasing use of single-stage surgery. We use antibiotic-loaded cement whenever possible but can reconstruct most cases using semiconstrained implants without resorting to a hinge. We continue to see a lower reinfection rate in these carefully selected patients, with high rates of infection control and satisfaction and better functional and quality of life scores than our two-stage revision cases. We use hinge reconstruction in less than 20% of cases

Prevention and treatment of total joint infection is closely related to biofilm formation and concentration of antibiotics achieved in the area around the implants. Most total joint infections are caused by bacteria that enter the wound at the time of the operation. These bacteria can attach to surfaces and rapidly form biofilm that is highly resistant to antibiotics. Prophylactic antibiotics given intravenously achieve concentration of local antibiotics in the knee in response to intravenous antibiotics about 1/3 of that achieved in the serum, and the level is transient. This may be enough to treat the planktonic form of the bacteria, but far from enough to treat the biofilm. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and cost analysis shows remarkable monetary benefit to this effect. Infected total joints benefit especially from direct application of antibiotics to the local area. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were thousands of times higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics. Preventing and treating infection in orthopaedic implant surgery requires achieving concentrations that are above the minimal biofilm eradication concentration. This can be achieved only with direct application

INTRO. Two-stage revision arthroplasty for PJI may make use of an antibiotic-loaded cement spacer (ACS), as successful long- term prevention of reinfection have been reported using this technique.[i] However, there is little data on systemic complications of high-dose antibiotic spacers. Acute kidney injury (AKI) is of clinical significance, as the drugs most commonly utilized, vancomycin and aminoglycosides, can be nephrotoxic. We intended to determine the incidence of AKI in patients that underwent staged revision arthroplasty with an ACS, as well as to identify potential predisposing risk factors for the disease. METHODS. Local databases of six different orthopaedic surgeons were retrospectively reviewed for insertion of either a static or articulating antibiotic cement spacer by from 2007–2017. Dose of antibiotic powder implanted, as well as IV antibiotic used, was collected from operative records. Demographics, comorbidities, and preoperative and postoperative creatinine and hemoglobin values were recorded from the EHR. AKI was defined by a more than 50% rise in serum creatinine from preoperative baseline to at least 1.4 mg/dL, as described by Menge et al.[ii] Variables were analyzed for the primary outcome of AKI within the same hospital stay as insertion of the ACS. Categorical variables were analyzed with Chi-Square test, and continuous variables with univariate logistic regression. RESULTS. 75 patients (39 M, 36 F) receiving an ACS were identified, with a mean age of 70.0 (SD=10.6) and a mean BMI of 31.3 (SD=7.3). Incidence of in-hospital AKI was 13.3%. Patients reached AKI at a mean 6.7 days (SD=4.5), during a median length of stay of 13.5 days (IQR=21.8). No significant correlation was found between AKI and the variables of age (p=.430), BMI (p=.569) or gender (p=.181). AKI was also not associated with increased dose of vancomycin (p=.416), tobramycin (p=.440), or gentamycin (p=.846) within the cement spacer, or the comorbidities of hypertension (p=.094), diabetes (p=.146), coronary artery disease (p=1.00) and renal disease (p=.521). However, decreased baseline hemoglobin showed significantly increased risk for AKI (OR=1.67, p =.049), and increased creatinine showed a trend (OR=2.9, p=.059). Percentage of hemoglobin decrease (preoperative to postoperative) did not increase odds for AKI (p=.700). CONCLUSION. The incidence of acute kidney injury in patients that receive antibiotic cement spacers is relatively high when compared to the data reported in primary TKA. ii,[iii]. Our results suggest that patient related risk factors, such as low preoperative hemoglobin, may be involved in the etiology of AKI in this population. Therefore, it may be clinically appropriate to monitor anemic patients for AKI when implanting an ACS