The majority of patients with prosthetic joint replacement (arthroplasty) experience dramatic relief of pain and restoration of satisfactory joint function. In the United States, more than .5 million people have a primary arthroplasty each year. Less than 10% of prosthesis recipients have complications develop during their lifetime, commonly as a result of aseptic biomechanical failure, followed by prosthetic joint infection. The pathogenesis of prosthetic joint infection is related to bacteria in biofilms, in which they are protected from antimicrobial killing and host responses rendering these infections difficult to eradicate. Current microbiology laboratory methods for diagnosis of prosthetic joint infection depend on isolation of a pathogen by culture. However, these methods have neither ideal sensitivity nor ideal specificity. Therefore, culture-independent molecular methods have been used to improve the diagnosis of prosthetic joint infection. In the research setting, detection of 16S ribosomal deoxyribonucleic acid by polymerase chain reaction has been used in the molecular diagnosis of prosthetic joint infection. Various antibiofilm strategies directed at disruption of adherent bacteria are the focus of intense research to improve the detection of biofilm organisms and their eradication. In this article, molecular and antibiofilm approaches to prosthetic joint infection are reviewed.

Molecular and antibiofilm approaches to prosthetic joint infection : Proceedings of the musculoskeletal Infection Society 2002

Infections in orthopaedic surgery are a serious issue. Antibiotic-loaded bone cement was developed for the treatment of infected joint arthroplasties and for prophylaxes in total joint replacement in selected cases. Despite the widespread use of the antibiotic-loaded bone cement in orthopedics, many issues are still unclear or controversial: bacterial adhesion and antibiotic resistance, modification of mechanical properties which follows the addition of the antibiotic, factors influencing the release of the antibiotic from the cement and the role of the surface, the method for mixing the cement and the antibiotic, the choice and the effectiveness of the antibiotic, the combination of two or more antibiotics, and the toxicity. This review discusses all these topics, focusing on properties, merits, and defects of the antibiotic loaded cement. The final objective is to provide the orthopaedic surgeons clear and concise information for the correct choice of cement in their clinical practice.

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Antibiotic-loaded cement in orthopedic surgery: a review.

Sonication cultures of explanted components as an add-on test to routinely conducted microbiological diagnostics improve pathogen detection

This prospective study compared PCR and culture techniques in the diagnosis of prosthetic joint infection (PJI). We obtained joint fluid samples (JFS; n=115) from patients who had failed total joint arthroplasty between January 2003 and June 2005; 49 were positive for PJI according to established strict criteria. JFS were analyzed by PCR (n=35; control n=66) or culture (n=46, control n=48). PCR was positive in 71% of PJI cases, resulting in sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and likelihood ratio for positive results as follows: 0.71; 0.97; 0.88; 0.93; 0.87 and 23.6, respectively. Culture was positive in 44% of PJI samples. Corresponding statistics were 0.44; 0.94; 0.69; 0.87; 0.63 and 7.0, respectively. Significantly higher sensitivity, accuracy and negative predictive values were calculated for PCR versus culture, and there was 83% concordance between the results of intraoperative culture and PCR detection of causative bacteria. Therefore, we conclude that PCR analysis of synovial fluid increases the utility of pre-operative aspiration for patients who require revision total joint surgery.

Culture and PCR analysis of joint fluid in the diagnosis of prosthetic joint infection.

Background: The diagnosis of periprosthetic joint infection poses many challenges, one of which is the difficulty of isolating the infecting organism. Recently, a sophisticated modality (the Ibis Biosciences T5000 biosensor system) has been introduced that uses pan-domain primers in a series of polymerase chain reactions (PCRs) to identify and speciate essentially all bacteria and fungi as well as to identify key antibiotic resistance genes. We investigated the role of the Ibis in identifying infecting organisms in cases of known and suspected periprosthetic joint infection.

Methods: Synovial fluid specimens were collected prospectively from eighty-two patients undergoing eighty-seven arthroplasty procedures (sixty-five knee revisions, fifteen hip revisions, and seven primary knee arthroplasties) and were sent for both conventional culture and Ibis analysis. The surgeon’s clinical determination of the cause for revision arthroplasty was failure due to infection in twenty-three cases and noninfectious failure in fifty-seven cases.

Results: In the twenty-three cases that were considered on clinical grounds to involve a periprosthetic joint infection, the Ibis detected the same pathogen isolated by conventional culture in seventeen of eighteen cases and also detected one or more organisms in four of the five culture-negative cases. In addition, the Ibis detected organisms in fifty (88%) of the fifty-seven cases in which revision arthroplasty was performed for a presumed noninfectious failure.

Conclusions: The Ibis technology was not only effective at detecting organisms in cases of suspected periprosthetic joint infection in which cultures were negative, but it also suggested that many of the revision arthroplasty cases that have previously been considered to be purely aseptic may have a component of unrecognized, subclinical infection.

Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection.

Prosthetic joint infection (PJI) diagnosis includes several classes of verification. Among them, only a few have a stronger independent value, namely intraarticular purulence and communicating fistulas. Other diagnostic methods require careful test combinations, analysis, and interpretation. Molecular based techniques using the polymerase chain reaction (PCR) seem to be a promising PJI diagnostic modality due to its excellent sensitivity, specificity, positive predictive value, and speed. Most of the recent reviewers are in agreement that molecular diagnosis has enough potential for future application in orthopaedics even if there are only a few heterogeneous studies fully supporting this concept. Conversely, at least one study has been published with significantly worse results (sensitivity and specificity less than 0.75). The lack of supporting evidence in the published studies may be closely related to varying PCR laboratory procedures, inappropriate reference standards, and other methodological shortcomings among research centers. It is not yet justifiable to firmly include molecular methods into the present PJI diagnostic schemes. The orthopaedic community must await the results of well-organized ongoing studies before considering inclusion of molecular diagnostics as a PJI diagnostic method. The aim of this paper was to make a survey of current PJI molecular diagnostic techniques in orhopaedics.

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Molecular diagnosis of prosthetic joint infection. A review of evidence.

Sepsis is a greatly feared complication of total joint arthroplasty. One key question is how to prevent perioperative bacterial adherence, and therefore the potential for infectious complications. The objective of our study was to appraise the emerging capacity of staphylococcal survival on prosthetic materials and to analyze the in vitro effects of gentamicin and vancomycin loaded polymethylmethacrylate (PMMA) cement on bacterial adherence and growth. Hospital acquired staphylococcal strains were systematically inoculated on four orthopedic materials (ultrahigh molecular weight polyethylene, PMMA without antibiotic, commercially produced PMMA loaded with gentamicin, and manually mixed PMMA loaded with gentamicin and vancomycin). Staphylococci were identified using culture and biochemical tests. The inoculated material was allowed to incubate in a liquid broth growth media and subsequently prepared for scanning electron microscopy and bacterial growth quantification. Materials without antibiotics showed evidence of staphylococcal growth. PMMA loaded with only gentamicin grew methicillin-resistant Staphylococcus aureus. Gentamicin-vancomycin loaded PMMA completely inhibited any bacterial growth. Low-dose gentamicin-vancomycin loaded PMMA prevents staphylococcal colonization better than commercially manufactured PMMA loaded with gentamicin. We recommend this combination in high-risk procedures and revision surgeries requiring bone cement.

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In vitro testing of gentamicin-vancomycin loaded bone cement to prevent prosthetic joint infection.

In this report, we present the case of a 64-year-old woman who sustained a Burch-Schneider cage fracture. Prior to this event, she underwent repeated acetabular reconstructions, but in the end prosthesis removal was performed as a salvage procedure. We believe that the primary cause of the fracture was metal fatigue facilitated by intraoperative re-contouring of the flange, as well as reuse of the cage. Based on this case we caution against repetitive or excessive flange bending during implantation of Burch-Schneider cages and do not recommend their reuse.

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Burch-Schneider cage fracture: a case report.

Sepsis is a greatly feared complication of total joint
arthroplasty. One key question is how to prevent periopera-tive
bacterial adherence, and therefore the potential for infectious
complications. The objective of our study was to appraise the
emerging capacity of staphylococcal survival on prosthetic
materials and to analyze the in vitro eects of gentamicin and
vancomycin loaded polymethylmethacrylate (PMMA) cement on
bacterial adherence and growth. Hospital acquired
staphylococcal strains were systematically inoculated on four
orthopedic materials (ultrahigh mo-lecular weight polyethylene,
PMMA without antibiotic, commercially produced PMMA loaded with
gentamicin, and manually mixed PMMA loaded with gentamicin and
vancomycin). Staphylococci were identied using culture and
biochemical tests. The inoculated material was allowed to
incubate in a liquid broth growth media and subsequently
prepared for scanning electron microscopy and bacterial growth
quantication. Materials without antibiotics showed evidence of
staphylococcal growth. PMMA loaded with only gentamicin grew
methicillin-resistant Staphylococcus aureus.
Gentamicin-vancomycin loaded PMMA completely inhibited any
bacterial growth.Low-dose gentamicin-vancomycin loaded PMMA
prevents staphylococcal colonization better than commercially
manufactured PMMA loaded with gentamicin. We recommend this
combination in high-risk procedures and revision surgeries
requiring bone cement.

Anthony V Florschütz

Papers

Molecular diagnosis of prosthetic joint infection. A review of evidence.

In vitro testing of gentamicin-vancomycin loaded bone cement to prevent prosthetic joint infection.

Burch-Schneider cage fracture: a case report.

In vitro testing of vancomycin - gentamicin loaded bone cementto prevent prosthetic joint infection