Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Aims. We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach. Methods. We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography. Results. The peak concentrations of vancomycin and meropenem in the joint cavity were observed at one hour post-injection, with mean values of 14,933.9 µg/ml (SD 10,176.3) and 5,819.1 µg/ml (SD 6,029.8), respectively. The trough concentrations at 24 hours were 5,495.0 µg/ml (SD 2,360.5) for vancomycin and 186.4 µg/ml (SD 254.3) for meropenem. The half-life of vancomycin was 6 hours, while that of meropenem ranged between 2 and 3.5 hours. No significant adverse events related to the antibiotic administration were observed. Conclusion. This method can achieve sustained high antibiotic concentrations within the joint space, exceeding the reported minimum biofilm eradication concentration. Our study highlights the remarkable effectiveness of intra-articular antibiotic infusion in delivering high intra-articular concentrations of antibiotics. The method provided sustained high antibiotic concentrations within the joint cavity, and no severe side-effects were observed. These findings offer evidence to improve clinical treatment strategies. However, further validation is required through studies with larger sample sizes and higher levels of evidence. Cite this article: Bone Joint Res 2024;13(10):535–545

Aims

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

Aim

The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality.

Aims. Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

Aims. Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. Methods. A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Results. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months (24 to 133). The seven-year infection-free survival was 87.6% (95% confidence interval (CI) 79.4 to 95.8). No significant difference in infection-free survival was observed between hip and knee PJIs (91.5% (95% CI 79.9 to 100) vs 84.7% (95% CI 73.1 to 96.3); p = 0.648). The mean postoperative Harris Hip Score was 76.1 points (63.2 to 92.4) and Hospital for Special Surgery score was 78. 2 (63.2 to 92.4) at the most recent assessment. Polymicrobial and fungal infections accounted for 14.1% (11/78) and 9.0% (7/78) of all cases, respectively. Conclusion. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid, thereby overcoming reduced vascular supply and biofilm formation. This supplementary route of administration may be a viable option in treating PJI after multiple failed prior surgeries for reinfection. Cite this article: Bone Joint J 2022;104-B(7):867–874

Aims

Single-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone.

Prosthetic joint infections (PJIs) with prior multiple failed surgeries for re-infection (PMFSR) represented a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion for treatment of PJIs with PMFSR. A retrospective analysis included 78 PJIs (29 hips; 49 knees) with PMFSR, who were treated with single-stage revision using intra-articular antibiotic infusion. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, a intra-articular infusion of vancomycin, imipenem or voriconazole was performed post-operatively. The antibiotic solution was soaked into the joint for 24 hours then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Of these 78 patients, 59 had more than twice failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, 3 hips underwent a failed two-stage revision and 4 cases had a failed one-stage revision before their single-stage revision. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months. No significant difference in infection control rate was observed between hip and knee PJIs (89.7% versus 85.7%). The mean postoperative Harris hip score was 76.1 points and HSS score was 78. 2 at the most recent assessment. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid therefore overcome poor vascular supply and biofilm formation, which can be a viable option in treating PJI with PMFSR

Aims

One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions.

Aims. In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI. Methods. A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups. Results. Of 51 CN patients, 46 (90.2%) required no additional medical treatment for recurrent infection at a mean of 53.2 months (24 to 72) of follow-up. Impaired kidney function occurred in two patients, and one patient had a local skin rash. No significant difference in the infection control rate was observed between CN and CP PJIs (90.2% (46/51) versus 94.3% (181/192); p = 0.297). The HHS of the CN group showed no substantial difference from that of CP cases (79 versus 81; p = 0.359). However, the CN group showed a mean HSS inferior to that of the CP group (76 versus 80; p = 0.027). Conclusion. Single-stage revision with direct intra-articular antibiotic infusion can be effective in treating CN PJI, and can achieve an infection control rate similar to that in CP patients. However, in view of systemic toxicity, local adverse reactions, and higher costs, additional strong evidence is needed to verify these treatment regimens. Cite this article: Bone Joint J 2020;102-B(3):336–344

Aims. Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants. Patients and Methods. Between 2010 and 2016, 126 patients underwent routine single-stage revision with cementless reconstruction with powdered vancomycin or imipenem poured into the medullary cavity and re-implantation of cementless components. For patients with a culture-negative hip, fungal infections, and multidrug-resistant organisms, a direct intra-articular infusion of pathogen-sensitive antibiotics was performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. Three patients died and 12 patients (none with known recurrent infection) were lost to follow-up. There were 111 remaining patients (60 male, 51 female) with a mean age of 58.7 (. sd. 12.7; 20 to 79). Results. Of these 111 patients, 99 (89.2%) were free of infection at a mean follow-up time of 58 months (24 to 107). A recurrent infection was observed in four of the 23 patients (17.4%) with culture-negative infected hip. The success rate in patients with multidrug-resistant organisms was 84.2% (16/19). The mean postoperative Harris hip score was 79.6 points (63 to 92) at the most recent assessment. Conclusion. Routine single-stage revision with cementless reconstruction can be a viable option for the treatment of chronically infected THA. The results of this study will add to the growing body of evidence supporting routine use of single-stage revision for the treatment of chronically infected THA. Cite this article: Bone Joint J 2019;101-B:396–402

Objectives

Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro.

Objectives

Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations.

Intra-articular infusions of adipose tissue-derived stem cells (ASCs) are a promising tool for bone regenerative medicine, thanks to their multilineage differentiating ability. One major limitation of ASCs is represented by the necessity to be isolated and expanded through in vitro culture, thus a strong interest was generated by the adipose stromal vascular fraction (SVF), the non-cultured fraction of ASCs. Besides the easiness of retrieval, handling and good availability, SVF is a heterogeneous population able to differentiate in vitro into osteoblasts, chondrocytes and adipocytes, according to the different stimuli received. We investigated and compared the bone regenerative potential of SVF and ASCs, through their ability to grow on SmartBone. ®. , a composite xenohybrid bone scaffold. SVF plated on SmartBone. ®. showed better osteoinductive capabilities than ASCs. Collagen I, osteocalcin and TGF↕ markedly stained the new tissue on SmartBone. ®. ; microCT analysis indicated a progressive increase in mineralised tissue apposition by quantification of newly formed trabeculae (3391 ± 270,5 vs 1825 ± 133,4, p± 0,001); an increased secretion of soluble factors stimulating osteoblasts, as VEGF (153,5 to 1278,1 pg/ml) and endothelin 1 (0,43 to 1,47 pg/ml), was detected over time. In conclusion, the usage of SVF, whose handling doesn't require manipulation in an in vitro culture, could definitively represent a benefit for a larger use in clinical applications. Our data strongly support an innovative idea for a bone regenerative medicine based on resorbable scaffold seeded with SVF, which will improve the precision of stem cells implant and the quality of new bone formation

Although single-stage revision has attracted a lot of attention due to less socioeconomic cost, this technique is not widely used throughout the world due to strict indications. In this situation, we report our outcome on single-stage revision combined with selective direct intra-articular antibiotic infusion for chronic infected THA, especially for patients with culture-negative hip, fungal infections and multidrug-resistant organism. We retrospectively reviewed 131 patients with chronic infected THA between January 2010 and February 2017 who underwent single-stage revision, including soakage of surgical area with 0.5% aqueous betadine, pouring powdered vancomycin or imipenem into the medullary cavity. For patients with culture-negative hip, fungal infections and multidrug-resistant organism, a direct intra-articular infusion of pathogens-sensitive antibiotics via three-branch catheter were performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. One hundred and fifteen patients were followed-up for an average of 4.5 years (range, 1.2–8 years). Of the 115 patients, 103 patients (89.6%) required no additional surgical or medical treatment for recurrence of infection. A recurrent infection was observed in 4 of the 23 patients (17.4%) with culture-negative infected hip. One of 4 fungal infections was relapse and the success rate in patients with multidrug-resistant organism was 84.2% (16/19). The mean postoperative Harris hip score was 81 points (63 to 92; p < 0.05) at the most recent assessment. Treatment of chronic infected THA by single-stage revision combined with selective direct intra-articular antibiotic infusion can be fairly effective, even for patients with relative “contraindication” of this approach

Total hip arthroplasty (THA) is reliable and reproducible in relieving pain and improving function in patients with end-stage arthritis of the hip joint. With improvements in surgical technique and advances in implant and instrument design, there has been a shift in focus from the technical aspects of the surgical procedure to improving the overall patient experience. In addition, shifts in medico-economic trends placed a premium on early patient mobilization, early discharge, and maximizing patient satisfaction. Arguably, a single most important advance in arthroplasty over the past 2 decades has been the development of multimodal pain protocols that form the foundation of many of the rapid recovery protocols today. The principal concept of multimodal analgesia is pain reduction through the utilization of multiple agents that synergistically act at various nodes of the pain pathway, thus, minimizing patient exposure to each individual agent and opioids in order to prevent opioid related adverse events (ORAE). Regional anesthesia has been shown to reduce post-operative pain, morphine consumption, and nausea and vomiting compared to general anesthesia but not length of stay. Additionally, general anesthesia has been shown to be associated with increased rates of post-operative adverse events, The use of peripheral nerve blocks in the form of sciatic, femoral or fascia iliaca blocks have not been shown to significantly reduce post-operative pain compared to controls. Periarticular infiltration of local anesthetics has been shown in some settings to reduce pain during the immediate post-operative period (<24 h). However, no significant differences were noted in terms of early recovery or complications. The use of liposomal bupivacaine (LB) local infiltration decreased pain and shortened length of stay comparable to patients receiving a fascia iliaca compartment block, and has been shown in relatively few randomised trials to provide improved pain relief at 24 hours only compared to conventional bupivacaine. Continuous intra-articular infusion of bupivacaine after THA did not significantly further reduce post-operative pain compared to placebo. In summary, the use of regional anesthesia when appropriate along with local anesthetic infiltration in the setting of a robust multimodal pain protocol minimises pain and complications while maximizing patient satisfaction following THA

Objective. The purpose of this study was to evaluate the efficacy and safety of the drained-clamped method with intra-articular infusion of tranexamic acid (TA) for reducing blood loss in total knee arthroplasty (TKA). Material and Methods. From November 2011 to July 2014 inclusive, 72 patients with a diagnosis of osteoarthritis underwent unilateral primary TKA using a computed tomography (CT) free navigation system. Patients were randomly divided into two groups: group T (n=40) was given 2000 mg (40 ml) of TA and group W (n=32) was given 40 ml sterile saline only. All operations were performed under total anaesthesia through the medial mid-vastus approach. Cemented posterior stabilised or cruciate retaining prostheses were used. The patella was resurfaced. After tourniquet release and wound suture, TA or saline was infused into the knee joint in addition to the drained-clamped method for 2 hours. For VTE prophylaxis, all patients received bilateral intermittent pneumatic calf compressors, thromboembolic deterrent stockings, and subcutaneous injection of enoxaparin (4000IU daily). We evaluated the hematocrit, hemoglobin and the postoperative estimate of bleeding. At postoperative days 4, extremity venous ultrasonography was performed for the investigation of venous thromboembolism in the latest 40 patients and contrast-enhanced CT was performed in the latest 34 patients without a previous history of asthma and diminished renal function. The present study received institutional review board approval, and informed consent was obtained from all patients. Results. Group T had lower hematocrit and hemoglobin levels at postoperative day 1. Group T had higher hemoglobin levels at postoperative days 3 and 7, respectively. The postoperative estimate of bleeding in group T was 739.2 ± 318.9 ml on average, which was significantly less than group W which was 999.8 ± 414.1 ml (p <0.01). The rate of asymptomatic deep vein thrombosis and pulmonary embolism was 57.1% and 29.4% in group T, and 36.8% and 11.8% in group W, respectively. There were no significant differences between the two groups. Conclusion. The drain-clamped method with intra-articular infusion of TA was safe and effective for reducing the amount of blood loss in TKA, without increasing the risk of VTE

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.

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.

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.