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Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 82 - 83
1 Mar 2006
Panousis K Grigoris P Butcher I Rana B Reilly J Hamblen D
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Introduction: Infection is a serious complication of joint arthroplasty. Detection of low-grade prosthetic infection can be difficult, with major implications on the subsequent treatment, cost and patient morbidity. We evaluated the effectiveness of Polymerase Chain Reaction (PCR) in detecting infection in patients undergoing arthroplasty revision surgery.

Methods: Ninety-one consecutive patients (92 joints) undergoing revision THA or TKA were assessed prospectively. Preoperative assessment included clinical examination, blood tests and plain radiographs. At revision, tissue samples were sent for microbiology and histology. Cultures, using blood culture bottles, and PCR were performed on the synovial fluid. Diagnosis of infection relied on the surgeon’s opinion encompassing the clinical presentation, the results of various investigations and the intraoperative findings. Infected arthroplasties underwent a 2-stage revision. Post-operatively patients were followed up at regular intervals for a minimum of 2 years.

Results: Twelve (13%) joints were infected. Histology was positive for infection in 11 cases, tissue cultures were positive in 12 and PCR was positive in 32 cases. Intraoperative tissue cultures had sensitivity 0.75, specificity 0.96, positive predictive value 0.75 and negative predictive value 0.96; histology had sensitivity 0.92, specificity 1, positive predictive value 1 and negative predictive value 0.99 and PCR had a sensitivity 0.92, specificity 0.74, positive predictive value 0.34 and negative predictive value 0.98. At 2 years no patient showed evidence of infection.

Discussion: PCR is a sensitive method of diagnosing prosthetic infection but has poor specificity. False positive results may be due to contamination in theatre or in the laboratory. Positive results in apparently non-infected cases could be due to the detection of low virulence organisms, a small number of bacteria or a strong host immune response. Bacterial fragments and non-culturable forms of bacteria may also be responsible.

Conclusion: PCR was not helpful as a screening test for prosthetic infection. Cultures and histology combined with the surgeon’s clinical judgment remain the gold standard.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_III | Pages 217 - 217
1 Mar 2003
Panousis K Rana B Reilly J Butcher I Crigoris P
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Introduction: Infection constitutes a serious complication of joint arthroplasty, with an incidence of 1–2% after primary arthroplasty and even higher after revision procedures. Detection of low-grade infection in a prosthetic joint can often be very difficult, with huge implications on the subsequent treatment, cost and patient morbidity. Revision of an unrecognised infected arthroplasty may lead to less satisfactory results in a high proportion of cases. We utilized Polymerase Chain Reaction, a molecular biology technique to detect bacterial DNA from the synovial fluid of patients undergoing revision surgery, in comparison with conventional infection detection techniques.

Methods: We prospectively assessed 81 patients undergoing revision arthroplasty (67 hips and 14 knees). Each patient was pre-operatively assessed clinically and radiologically. ESR and CRP results were noted. During revision, synovial fluid and tissue cultures were obtained and antibiotics were given only after the specimens were taken. Standard microbiology and histology study were done on tissue samples. In addition Polymerase Chain Reaction study was performed on the synovial fluid. In this method, DNA is extracted from the bacterial cell; it is polymerised and finally visualized by gel electrophoresis. Post-operatively patients were followed up at regular intervals. Diagnosis of infection included correlation between clinical, radiological and laboratory investigations along with intra-operative findings, tissue culture and histology results and a period of postoperative follow up of 12 to 36 months.

Results: Eleven (13.58%) of the 81 cases that had revision arthroplasty were clinically infected. Polymerase chain reaction was positive in 30 cases, tissue cultures were positive in 8 cases and histology was positive in 10 cases for infection. PCR showed sensitivity and specificity of 0.92 and 0.72 respectively. Tissue culture showed sensitivity and specificity of 0.72 and 0.81 respectively. Histology showed sensitivity and specificity of 0.9 and 1 respectively.

Discussion: Twenty out of 30 PCR positive cases did not show any clinical evidence of infection. It is unclear whether this represents contamination during surgery or in the PCR lab. Alternatively this may represent true positive PCR results in cases with low bacterial count or bacteria growing within a biofilm that can be detected only by ultrasonication of the implant and immunofluorescence methods. PCR could also be detecting non-culturable forms of bacteria or bacterial fragments.

Conclusion: PCR has high sensitivity and low specificity for detection of bacterial DNA. The combination of tissue cultures and histology can still provide a reliable diagnosis of infection.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 125 - 125
1 Feb 2003
Rana B Grigoris P Shetty S Reilly J Butcher I Hamblen DL
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The incidence of infection remains 1–2% after primary total joint arthroplasty and even higher after revision procedures in spite of advances in prophylactic antibiotics and clean air operating theatre environment. Detection of low-grade infection in a prosthetic joint can often be very difficult. None of the investigations available so far have 100% sensitivity and specificity. This has huge implications on the subsequent treatment, cost and patient morbidity. Revision of an unrecognized infected arthroplasty may lead to less satisfactory results in a high proportion of cases. We utilized Polymerase Chain Reaction, a molecular biology technique to detect bacterial DNA from the synovial fluid of patients undergoing revision surgery.

We prospectively assessed 70 patients undergoing revision arthroplasty (57 hips and 13 knees). Each patient was pre operatively assessed clinically and radiologically. ESR and CRP results were noted. During revision, synovial fluid and tissue cultures from capsule, bone and bone-cement interface were obtained. None of the patients received pre or intra operative antibiotics till the specimens were taken. Standard microbiology and histology study were done on tissue samples. In addition Polymerase Chain Reaction study was done on the synovial fluid. In this method, DNA is extracted from the bacterial cell, it is polymerized and finally visualized by gel electrophoresis. Post operatively patients were followed up at regular intervals.

Diagnosis of infection included correlation between clinical, radiological and laboratory investigations along with intraoperative findings, tissue culture and histology results and a period of post operative follow up (12 months to 36 months).

Six (8%) of the 70 cases that had revision arthroplasty were clinically infected. Polymerase chain reaction was positive in 25 cases, tissue cultures were positive in 5 cases and histology was positive in 5 cases for infection. PCR showed sensitivity and specificity of 83% and 69% respectively. Tissue culture showed sensitivity and specificity of 83% and 100% respectively. Histology showed sensitivity and specificity of 83% and 100% respectively.

20 out of 25 PCR positive cases did not show any clinical evidence of infection. It is unclear whether this represents contamination during surgery or in the PCR lab. Alternatively this may represent true positive PCR results in cases with low bacterial count that can be detected by ultrasonication of implant and immunofluorescence methods. PCR is more sensitive in detection of bacterial DNA. However it has low specificity and combination of tissue cultures and histology can still provide a reliable diagnosis of infection.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 16 - 16
1 Jan 2003
Rana B Murnaghan C Butcher I Seaton R Grigoris P
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Therapy against Methicillin resistant Staphylococcus aureus (MRSA) infection is mainly restricted to the glycopeptide agents (vancomycin and teicoplanin), which require parenteral administration. At present oral antibiotic therapy against MRSA infection is not available. Linezolid is a recently introduced oxazolidinone synthetic antibiotic which acts by inhibiting the initiation of bacterial protein synthesis. It is effective against MRSA, glycopeptide resistant enterococci and all pneumococci irrespective of their penicillin or macrolide resistance. It has excellent oral bioavailability however, there are no data on the penetration of linezolid into osteoarticular tissues. This aim f this study was to measure the concentration of Linezolid in osteoarticular tissues after oral and intravenous administration.

Ten patients undergoing primary total knee replacements for osteoarthritis or rheumatoid arthritis were included in the study. Linezolid was given orally 600mg BD dose for 2 days prior to operation and a final IV 600mg dose 1h before induction on the day of operation. Intra-operatively at 30min after induction, blood, synovial fluid, synovium, muscle and bone samples were collected, processed and assayed for Linezolid concentration. The assay was performed by High Performance Liquid Chromatography (HPLC) method at Antimicrobial Research Laboratory, Westmead Hospital, Bristol.

High concentrations of Linezolid, above the Minimum Inhibitory Concentration (MIC≤ 4) were obtained all sites. Mean (± SD) concentrations for different tis- were: serum 23.0 (6.5) mg/L, synovial fluid 20.1 .4) mg/L, synovium 18.0 (5.6) mg/kg, muscle 18.5 (6.6) bone 8.5 (3.9) mg/kg

Treatment of Methicillin resistant Staphylococcus (MRSA) infections in bone and native or pros- joints is complex and costly. It requires prolonged parenteral and oral antibiotic combination therapy in addition to aggressive surgical debridement. The MICs Linezolid for staphylococci, pneumococci and streptococci are in a range from 0.5 to 2 mg/L whereas MIC enterococci is constant at 4mg/L. A two to six fold increased bioavailability of Linezolid was observed compared to its desired MIC. This study indicates that Linezolid penetrates osteoarticular tissues in sufficient concentration. Linezolid may prove to be an effective or intravenous therapy for serious bone and joint infections with multi-resistant gram-positive bacteria.


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 5 | Pages 725 - 727
1 Sep 1994
James P Butcher I Gardner E Hamblen D

We investigated the incidence of cephalosporin-resistant bacteria in infected hip arthroplasties. Of 740 patients having hip replacement or related procedures performed over three years, 30 had positive bacteriological cultures from tissue removed at the time of surgery. In 18 of the 30 cultures Staphylococcus epidermidis was grown and 12 of these were methicillin-resistant. A prospective study of skin swabs taken from 100 consecutive patients at the time of admission for THR showed methicillin-resistant Staphylococcus epidermidis in 25. This cephalosporin-resistant organism was shown to be the commonest proven cause of infection, and its presence as a skin commensal raises important questions about current antibiotic prophylaxis for joint replacement.