Aim

To evaluate the ability of different combinations of antibiotic loaded cement to inhibit bacteria growth and biofilm formation.

Cephalasporin antibiotics have been commonly used for prophylaxis against surgical site infection. To prevent Clostridium difficile, the preferential use of agents such as flucloxacillin and gentamicin has been recommended. The aim of this study was to investigate the bone penetration of these antibiotics during hip and knee arthroplasty, and their efficacy against Staphylococcus aureus and S. epidermidis.

Bone samples were collected from 21 patients undergoing total knee arthroplasty (TKA) and 18 patients undergoing total hip replacement (THA). The concentration of both antibiotics was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured using the epidemiological cut-off value for resistance (ECOFF).

The bone penetration of gentamicin was higher than flucloxacillin. The concentration of both antibiotics was higher in the acetabulum than the femoral head or neck (p=0.007 flucloxacillin; p=0.021 gentamicin). Flucloxacillin concentrations were effective against S. aureus and S. epidermis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S.epidermis in all bone samples. Gentamicin was effective against S. aureus in 11 (89%) femoral samples. Effective concentrations of gentamicin against S. aureus were only achieved in 4 (19%) femoral and 6 (29%) tibial samples in TKA.

Flucloxacillin and gentamicin was found to effectively penetrate bone during arthroplasty. Gentamicin was effective against S. epidermidis in both THA and TKA, while it was found to be less effective against S. aureus during TKA. Bone penetration of both antibiotics was less in TKA than THA.

Summary Statement

Developing titanium (Ti) surfaces that are biocompatible yet serve as deterrents for bacterial attachment and growth are particularly appealing in tackling the ongoing problem of sepsis-induced implant failures. Realising this could include coating Ti with the bioactive lipid, lysophosphatidic acid.

Summary Statement

Conventional culture techniques have poor sensitivity for detecting bacteria growing in biofilms, which can result in under-diagnosis of infections. Sonication of biofilm colonised orthopaedic biomaterials can render bacteria in biofilm more culturable, thereby improving diagnosis of orthopaedic implant infections.

It has been reported that some of the local anaesthetic agents possess antimicrobial activity against clinically-significant bacteria. Although bupivacaine exhibits a bacteriostatic effect at concentrations above 0.25% there are concerns that it might interact with some of the other antibiotics administered to patients. Whilst these interactions may be potentially benign, the risk is that they are antagonistic and that local bupivacaine might predispose the patient to a higher risk of infection.

Bupivacaine is commonly administered as a local anaesthetic following knee arthroplasy; the purpose of this study was to assess its potential interactions with gentamicin eluting from the cement used to fix the device.

A strain of Saphylococcus aureus (29213) with established susceptible Minimal Inhibition Concentration (MIC) and Minimal Bactericidal Concentration (MBC) for gentamicin was used. This organism was inoculated into four types of broth; Mueller-Hinton broth (MH), MH with different concentrations of gentamicin, MH with 0.25% and 0.125% bupivacaine and MH with various combinations of gentamicin and bupivacaine. The broths were incubated at 37C and at 0.5, 1, 2, 3, 6 and 24 hours post inoculation the number of bacteria remaining were counted. From these data kill-curves were generated describing the absolute and individual rates of killing seen with bupivacaine and gentamicin alone and when in combination.

Bupivacaine showed a bacteriostatic effect only at concentrations of 0.25% and higher. All concentrations of gentamicin above or equal to the expected MBC showed bactericidal effect. However, in combination with both strengths of Bupivacaine (0.25 and 0.125%) the bacteriocidal effect of gentamicin was seen at a lower concentration and the rate of killing of bacteria was enhanced.

Bupivacaine has bacteriostatic effect at concentrations above 0.25% in line with published data. In these experiments we have shown that the use of bupivacaine together with gentamicin does not reduce the bactericidal property of the antibiotic and that the bactericidal effect of gentamicin appears to be enhanced by bupivacaine. This would suggest that the local use of bupivacaine is unlikely to increase the risk of infection in patients undergoing knee arthroplasty and may actually be beneficial.

Prosthetic joint infection(PJI) still remains a concern in orthopaedic practice. Antibiotic-loaded acrylic-cement(ALAC) is a proven means of lowering the incidence of PJI. However, increasing antimicrobial resistance has complicated both prophylaxis and treatment, prompting the use of combination antimicrobial therapy, with the addition of vancomycin to gentamicin-containing ALAC commonly used. The new antimicrobial, daptomycin, has better activity than vancomycin and we studied its elution from ALAC in comparison with vancomycin, along with its impact on the co-elution of gentamicin.

Cement beads were prepared from PalacosRG containing, 1g/2g daptomycin, 1g/2g vancomycin and without additional antibiotics. Six replicates of each combination were eluted in PBS at 37oC, at timed intervals, for up to 90days, the antibiotic loss was assessed using validated assays.

The mean recovery of gentamicin after 90days was 1.1mg with half eluted within the first 6 hours. Recovery was significantly increased by 60% and 40% with addition of 1g&2g of daptomycin(two-tail t-test: p=0.004 and p=0.02), respectively. Although there was a slight increase in gentamicin recovery in vancomycin loaded samples, this was not statistically significant(p>0.05).

The significant increases in gentamicin elution from Palacos RG when supplemented with daptomycin, along with a superior activity, may provide a better synergistic effect than PalacosRG supplemented with vancomycin in the management of PJI.

Introduction: Avascular necrosis of the femoral head may play a role in failure of the femoral component in metal on metal hip resurfacing arthroplasty. The purpose of our study was to determine, prospectively, femoral head perfusion during hip resurfacing arthroplasty in the posterior and anterolateral approaches.

Methods: 20 hip resurfacing arthroplasties were performed in 19 patients between September 2005 and March 2006 by two different surgeons; one using the extended posterior approach and the other an anterolateral approach. There were an equal number of procedures for each approach. 1.5 gms of intravenous cefuroxime was administered following caspsulectomy and relocation of the femoral head. After 5 minutes the femoral head was dislocated and prepared as routine for the operation. Bone from the top of the femoral head and reamings were sent for assay to determine the concentration of cefuroxime. The average time taken to prepare the femur and take samples was 8.5 minutes.

Results: The concentration of cefuroxime in bone was significantly greater when using the anterolateral approach (mean 15.7mg/kg; CI 12.3 – 19.1) compared to the posterior approach (mean 5.6mg/kg; CI 3.5 – 7.8; p< 0.001). In one patient, who had the operation through a posterior approach, cefuroxime was undetectable.

Discussion: The posterior approach is associated with a significant reduction in the blood supply to the femoral head during hip resurfacing arthroplasty. This may be a cause for avascular necrosis and potential failure of the femoral component in this procedure.

Introduction: Dividing the short external rotators 2 cm from their insertion into the femur should preserve the deep branch of the medial femoral circumflex artery. Our aim was to determine, prospectively, femoral head perfusion during hip resurfacing arthroplasty comparing two posterior approaches.

Methods: 20 hip resurfacing arthroplasties were performed in 20 patients by two different surgeons between September 2005 and November 2006. Patients were divided into two equal groups according to approach. One surgeon used the extended posterior approach and the other a modified posterior approach. Intravenous cefuroxime was administered in every case following capsulectomy and relocation of the femoral head. After 5 minutes the femoral head was dislocated and prepared as routine for the operation. Bone from the top of the femoral head and reamings were sent for assay to determine the concentration of cefuroxime.

Results: There was no statistical difference between the concentration of cefuroxime in bone when using the modified posterior approach (mean 5.6mg/kg; CI 3.6 – 7.8) compared to the extended posterior approach (mean 5.6; CI 3.5 – 7.8; p=0.95). In one patient, who had the operation through the posterior approach, cefuroxime was undetectable.

Discussion: The similarity in femoral head perfusion between approaches suggests the blood supply is further impaired by capsulectomy rather than by damaging the MFCA alone.

Aim: Avascular necrosis of the femoral head is believed to play a role in failure of the femoral component in metal on metal hip resurfacing arthroplasty. The purpose of our study was to determine, prospectively, femoral head perfusion during hip resurfacing arthroplasty in the posterior and anterolateral approaches.

Methods: 20 hip resurfacing arthroplasties were performed in 19 patients between September 2005 and April 2006. Patients were divided into two groups according to approach. An equal number of operations were performed by two different surgeons; one using the extended posterior approach and the other an anterolateral approach. Intravenous cefuroxime was administered in every case following capsulectomy and relocation of the femoral head. After 5 minutes the femoral head was dislocated and prepared as routine for the operation. Bone from the top of the femoral head and reamings were sent for assay to determine the concentration of cefuroxime.

Results: The concentration of cefuroxime in bone was significantly greater when using the anterolateral approach (mean 15.7mg/kg; CI 12.3 to 19.1) compared to the posterior approach (mean 5.6mg/kg, CI 3.5 to 7.8; p< 0.001). In one patient, who had the operation through a posterior approach, cefuroxime was undetectable.

Conclusion: The posterior approach is associated with a significant reduction in the blood supply to the femoral head during hip resurfacing arthroplasty. This may be a cause for avascular necrosis and potential failure of the femoral component in this procedure.

The aim of this study was to measure intra-articular gentamicin levels at the 2^nd stage revision following the use of an antibiotic impregnated articulating spacer.

Infected total knee replacements are a cause of considerable morbidity often requiring revision in two stages. Rings of bone cement, cement moulds and spacer devices are available for use following the initial debridement and removal of infected metalwork. The availability of antibiotic impregnated articulating spacers are potentially attractive to achieve a high local dose of antibiotic and to maintain a good range of movement.

Seven patients underwent a two stage revision of their total knee replacements. Following the initial debridement an antibiotic impregnated articulating spacer was cemented in place. At the 2^nd stage revision a perioperative joint aspirate and blood sample was taken and gentamicin levels measured. The range of movement was assessed.

The average gentamicin levels were 0.72mg/l (0.24 – 2.36mg/l). A good range of movement was maintained in all cases. At these levels the gentamicin would be therapeutic.

Antibiotic impregnated articulating spacers possess several potential advantages to the revision knee surgeon by helping maintain the range of movement and provide local release of antibiotics. Their use should be considered in such cases.

Introduction: In-vivo elution studies on Antibiotic-loaded Bone Cement (ABC) have concentrated on the short to medium term. This unit has previously described gentamicin release from cement during revision surgery and its presence in the joint aspirates of THAs at up to 12 years. We elected to study the late elutional behaviour of gentamicin-loaded cement in THA.

Methods: 51 patients undergoing revision THA surgery, for aseptic failure, at our centre were studied. Details of the original operation and the subsequent clinical and radiographic course were noted. Pre-operative urine samples and intra-operative joint fluid aspirates (prior to cement disruption) were assayed for their gentamicin concentrations using a fluorescence polarisation immunoassay (Abbott TDX). Cement samples underwent a Bacillus subtilis agar plate inhibition bioassay to assess for antimicrobial activity.

Results: Urine samples were obtained in 43 (84%) of the cases. All were negative for gentamicin (sensitivity level of 0.06 mg/L). Cement samples were retrieved in 36 cases (71%) and all of these (100%) demonstrated significant antimicrobial activity when compared to a standard 10 mg gentamicin disc. In 25 cases (49%) the joints were aspirated and 8 (32%) of these had a gentamicin concentration > 0.1 mg/L. The concentrations however were all below the Minimum Inhibitory Concentration (MIC) for intermediate sensitivity organisms. The longest interval between the primary and revision operations, in these positive cases was 25 years!

Conclusions: This study uniquely demonstrates sequestration of gentamicin within cement for up to 27 years. In addition, one third of joint aspirates had detectable though subtherapeutic gentamicin concentrations at up to 25 years. There was no evidence of late systemic release. These low concentrations of antibiotics, released after many years, are probably a potent stimulus to the emergence of resistant organisms. The use of antibiotic-loaded bone cement in primary THA remains controversial and requires further scrutiny.