[Diagnosis of periprosthetic joint infection : Development of an evidence-based algorithm by the work group of implant-associated infection of the AE-(German Society for Arthroplasty)]. / Diagnostik der periprothetischen Infektion : Entwicklung eines evidenzbasierten Algorithmus der Arbeitsgruppe implantatassoziierte Infektion der Arbeitsgemeinschaft Endoprothetik.

BACKGROUND: Prosthetic joint infections (PPI) will challenge orthopaedic surgeons and the health care system in the coming years. Evidence-based and reliable preoperative diagnostics are necessary for success in the field of revision arthroplasty. Especially the preoperative detection of PPI is important with respect to the treatment strategy. AIM: The aim of this study was to develop a detailed and structured standard operating procedure (SOP) to detect PPI preoperatively. METHODS: A systematic literature research was performed and relevant articles identified. After extracting the data, statistical calculations of sensitivity, specificity, positive/negative predictive value and positive/negative likelihood ratio were performed. The results were discussed and evaluated in four meetings analogously to standard Delphi rounds by the workgroup of implant-associated infections of the German AE (Arbeitsgemeinschaft Endoprothetik). An algorithm for the diagnostic approach according to ISO 5807 was made. RESULTS: The standardized algorithm combines a sequence of evidence-based procedures with detailed and structured main and additional criteria to every critical step in the diagnostic approach. CONCLUSION: The detection of PPI is of tremendous importance prior to revision arthroplasty and determines its success or failure. The diagnosis "prosthetic joint infection" requires a substantial change with respect to treatment concepts. The algorithm summarizes current literature and specialized expert opinions in a modern standardized format for a transparent diagnostic approach.

[Use of antibiotics in bones : Prophylaxis and current treatment standards]. / Anwendung von Antibiotika im Knochen : Prophylaxe und aktuelle Therapiestandards.

BACKGROUND: Treatment of bone infection is difficult due the systemic administration of antibiotics, which means that only low concentrations reach the inflamed bone tissue. Loss of bone stock is common in osteomyelitis and device associated infection. Local antibiotics are administered in several ways for prophylactic purposes and also for treatment of bone infection. We intend to show the options and limitations of clinical use of antibiotic-loaded bone grafts. SUITABILITY: Bone grafts are a suitable carrier system for antibiotics. Bone grafts may be loaded with a variety of antimicrobial agents so that individual therapies may be carried out. Critical systemic side effects are unlikely even though extreme high drug concentrations are obtained locally, if the thresholds for loading with antibiotics are respected. Thus, antibiotic-loaded bone grafts are appropriate for prophylaxis and therapy as well. If processing is done in the operating theatre compliance to the legal rules must be respected. RULES: Due to a lack of standardised procedures for loading, application and performance of the application of antibiotic-loaded bone grafts medical societies are being asked to initiate consensus meetings in order to issue recommendations or guidelines with respect to antibiotic-loaded bone grafts to establish reliable rules for surgeons using these devices.

[CD15 focus score for diagnostics of periprosthetic joint infections : Neutrophilic granulocytes quantification mode and the development of morphometric software (CD15 quantifier)]. / CD15-Fokus-Score zur Diagnostik der periprothetischen Gelenkinfektion : Neutrophile-Granulozyten-Quantifizierungs-Modus und Entwicklung einer morphometrischen Software ("CD15-Quantifier").

BACKGROUND: The aim of this project was to devise a quantification method for neutrophils within a single focal point through the development of a CD15 focus score which enables bacterial infections in synovial-like interface membranes (SLIM) to be diagnosed. METHODS: In this study a histopathological classification of 91 SLIM removed during revision surgery from the hips (n = 59) and knees (n = 32) was performed. Neutrophils were identified immunohistochemically by means of a CD15-specific monoclonal antibody. The quantitative evaluation of CD15-positive neutrophils (CD15Ne) used the principle of maximum focal infiltration (focus) together with an assessment of a single focal point (0.3 mm(2)). This immunohistochemical approach made it possible to develop the CD15 quantifier software, which automatically quantifies CD15Ne. RESULTS: The SLIM cases with positive microbiological findings (n = 47) had significantly (p < 0.001, Mann-Whitney U-test) more CD15Ne/focal point than cases with negative microbiological findings (n = 44). A count of 50 CD15Ne/focal point was identified as the optimum threshold when diagnosing periprosthetic joint infections (PJI) using the CD15 focus score. If the microbiological findings are used as a gold standard, the diagnostic sensitivity is 0.83, and the specificity is 0.864 with a positive predictive value (PPV) of 0.87, a negative predictive value (NPV) of 0.83, an accuracy of 0.846 and an area under the curve (AUC) of 0.878. The evaluation of findings for the preparations using the CD15 quantifier software (n = 31) deviated by an average of 12 cells from the histopathological evaluation findings (CD15 focus score). Above a cell count of 62, the CD15-quantifier needs on average 32 s less than the pathologist. CONCLUSION: The immunohistochemical CD15 focus score has a high diagnostic value and allowed the development of the CD15 quantifier software. This provides an automated procedure, which shortens the mentally tiring and time-consuming process of microscopic cell counting and thus makes a contribution towards the standardization of tools for diagnosing PJI.

[Logistic requirements and biopsy of periprosthetic infections: what should be taken into consideration?]. / Logistische Voraussetzungen und Probenentnahme bei periprothetischen Infektionen: Was muss beachtet werden?

Preoperative diagnosis of periprosthetic infections is particularly important before revision of knee and hip arthroplasties because of the therapeutic consequences. Therefore, periprosthetic infections should be ruled out before any revision surgery is performed. Of the different diagnostic methods direct techniques which allow the direct detection of microorganisms with testing of antibiotic sensitivity are recommended. This allows microorganism-specific systemic and local antibiotic therapies and helps to reduce the risk of development of resistance. In our studies it could be shown that the time for incubation to detect microorganisms should be 14 days and that biopsy of periprosthetic tissues is superior to aspiration alone because it combines several diagnostic methods (microbiological and histological). It is preferable to repeating an aspiration when data are unclear, i.e. in cases of potentially false positives or negatives results of aspiration.

[Diagnosis and treatment of foreign-body-associated infection in orthopaedic surgery]. / Diagnostik und Therapie implantatassoziierter Infekte.

Periprosthetic infection is a foreign-body-associated infection that is characterised by delayed osteomyelitis of bone tissue surrounding artificial joint replacement. Most of these infections result from intraoperative bacterial contamination of the prosthetic device implanted. The period from contamination to clinically apparent infection can last months or even years. In these cases, the initial surgical procedure is often not blamed for the actual infection. Moreover, these infections often produce minimal symptoms that can be mistaken for aseptic loosening of the artificial joint replacement. The bacterial burden of the causative pathogen is low in these cases, a fact that need to be considered in the diagnostic procedures.Knowledge of the pathogenesis allows the orthopaedic surgeon to plan the diagnostic procedures and therapy as well. In this context, the pathogen's ability to form biofilm is of crucial significance and explains why it is necessary to remove the foreign body (prosthesis or other artificial devices, such as material used for osteosynthesis or spinal stabilisation) to control this type of infection. This article gives some basic information for better understanding of foreign-body-associated infection in order to improve diagnostics and therapy in the clinical routine.

Proposal for a histopathological consensus classification of the periprosthetic interface membrane.

AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.

One-stage exchange shoulder arthroplasty for peri-prosthetic infection.

There are few reports in the literature of the diagnosis and treatment of the infected shoulder arthroplasty. Most deal with resection arthroplasty and two-stage exchange surgery. We present our results of one-stage exchange operation as treatment for the infected shoulder arthroplasty. Our group comprised 16 patients (ten men, six women) with 16 infected arthroplasties. By the time of follow-up, two patients had died (mean 5.8 years), two could not be located and three had already undergone revision surgery. Nine patients were thus available for clinical examination and assessment. The infections were largely caused by staphylococci, Propionibacterium species and streptococci. Two were early infections (within three months of surgery) and 14 were late infections. The mean follow-up was 5.8 years (13 months to 13.25 years) when the mean Constant-Murley score was 33.6 points and the mean University College of Los Angeles score 18.3 points. Further revision was performed in three patients. One sustained a peri-prosthetic humeral fracture, another developed an acromial pseudarthrosis after transacromial surgery and the third suffered recurrent dislocations. No patient had a recurrence of infection. A one-stage exchange procedure using antibiotic-loaded bone cement eradicated infection in all our patients and we suggest that such a procedure is at least as successful as either a resection arthroplasty or a two-stage exchange in the management of the infected shoulder arthroplasty.

Is "aseptic" loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in patients with low-grade infection?

BACKGROUND: Loosening of the prosthetic cup is the limiting factor in the service life of total hip prostheses (THPs). Despite effective culture methods, the detection of low-grade infection in patients with loose implants still presents a challenge. It is crucial to distinguish between "aseptic" loosening and loosening due to periprosthetic infection, so that appropriate treatment can be administered. We investigated whether aseptic loosening of the acetabular components of THPs is due to unrecognized infection. METHODS: From October through December 2002, a total of 24 patients with acetabular cup loosening were investigated. Only patients without clinical signs of infection and with negative results of bacteriologic culture of synovial fluid (obtained by preoperative aspiration) were included in the study. Intraoperative biopsy samples obtained from the neocapsule and synovia (e.g., the interface membrane) were examined by means of routine culture methods and by polymerase chain reaction (PCR) for detection of 16S ribosomal RNA (rRNA). Control subjects included 9 patients undergoing primary hip arthroplasty. RESULTS: C-reactive protein levels and erythrocyte sedimentation rates were slightly elevated in the group with loosening, compared with the control group, but the difference was not statistically significant. PCR and routine culture showed no microorganisms in either group, with the exception of 1 patient in the loosening group. CONCLUSIONS: PCR for detection of 16S rRNA in tissue specimens obtained from hip joints is not superior to routine bacteriologic culture techniques for detection of low-grade infections. However, these results demonstrate that the loosening of cups in THPs do not usually result from nonculturable periprosthetic infection, if the microbiological processing is adequate.

[Therapy of bacterial knee joint infection by radical synovectomy and implantation of a cemented stabilized knee joint endoprosthesis]. / Therapie der bakteriellen Gonitis durch radikale Synovektomie und Einsetzen einer zementierten stabilisierten Kniegelenkendoprothese.

INTRODUCTION: The report presents an alternative to the treatment of joint destruction in cases of knee joint empyema by resection or arthrodesis: implantation of a stabilised knee prosthesis using antibiotic-loaded bone cement for fixation. METHOD: From 1985 to 1997 a total of 33 knees in 32 patients (21 female, 12 male) were treated for knee empyema by radical synovectomy and implantation of a stabilised knee prosthesis fixed in position with antibiotic-loaded bone cement. The antibiotics were chosen according to the antibiogram of the pathogen. In all these cases the infections had not responded to previous treatment. The criterion for success was the elimination of infection. The follow-up period ranged from 2 to 15 years. RESULTS: Of 33 infected knees 31 (93.9%) were followed up. In 22 cases (71.0%) the infection was eliminated by primary surgery. In five cases (16.1%) further exchange operations were necessary to eliminate the infection. In four cases (12.9%) preservation of the joint was not possible. CONCLUSION: Uncontrolled infection in cases of knee empyema and destruction of the joint can be treated by radical synovectomy and implantation of a stabilised knee prosthesis using antibiotic-loaded bone cement for fixation. The success rate corresponds to the results of one-stage exchange arthroplasty to treat periprosthetic infection of knee prostheses. This therapy should be performed only in specialised centres which have the facilities and personnel essential for accurate bacteriological diagnosis and recommendation.

Single-stage revision for fungal peri-prosthetic joint infection: a single-centre experience.

Fungal peri-prosthetic infections of the knee and hip are rare but likely to result in devastating complications. In this study we evaluated the results of their management using a single-stage exchange technique. Between 2001 and 2011, 14 patients (ten hips, four knees) were treated for a peri-prosthetic fungal infection. One patient was excluded because revision surgery was not possible owing to a large acetabular defect. One patient developed a further infection two months post-operatively and was excluded from the analysis. Two patients died of unrelated causes. After a mean of seven years (3 to 11) a total of ten patients were available for follow-up. One patient, undergoing revision replacement of the hip, had a post-operative dislocation. Another patient, undergoing revision replacement of the knee, developed a wound infection and required revision 29 months post-operatively following a peri-prosthetic femoral fracture. The mean Harris hip score increased to 74 points (63 to 84; p < 0.02) in those undergoing revision replacement of the hip, and the mean Hospital for Special Surgery knee score increased to 75 points (70 to 80; p < 0.01) in those undergoing revision replacement of the knee. A single-stage revision following fungal peri-prosthetic infection is feasible, with an acceptable rate of a satisfactory outcome.

Revised histopathological consensus classification of joint implant related pathology.

This extended classification of joint implant related pathology is a practical histopathologic classification based on defined morphological criteria covering the complete spectrum of pathohistologic changes in periprosthetic tissues. These changes may occur as a consequence of endoprosthetic replacement of large joints and may lead to a reduction in the prosthesis survival rate. We describe the established consensus classification of the periprosthetic membrane, in which aseptic and septic prosthetic loosening can be subdivided into four histological types, as well as histopathological criteria for additional significant pathologies including endoprosthetic-associated arthrofibrosis, particle-induced immunological, inflammatory and toxic mechanisms (adverse reactions), and bone tissue pathologies. These characteristic tissue alterations and their relationships are summarized in the extended classification. Since particle heterogeneity in periprosthetic tissue is high and particle identification is a necessary part of diagnosis, the identification of different types of particles is described in the histopathological particle algorithm. The morphological qualities of prosthetic material particles and the demarcation between abrasion and non-abrasion endogenous particles are also summarized. This feasible classification which is based on low cost standard tissue processing and examination and on well-defined diagnostic criteria is a solid platform for the histological diagnosis of implant associated pathologies providing a stable and reproducible tool for the surgical pathologist. Since this classification is suitable for standardized histopathological diagnostics, it might also provide a useful data set for joint arthroplasty registers, particularly for registers based on so-called routine data.

[Aspiration of joint fluid for detection of the pathogen in periprosthetic infection]. / Gelenkpunktat und Erregernachweis bei periprothetischer Infektion.

Periprosthetic infection is a rare but severe complication of a frequently performed procedure. The diagnosis of this mostly chronic infection is difficult due to the absence of classic signs of infection in one-third of the cases. In this context, periprosthetic infection may be proven by detecting the bacterial pathogen. Aspiration of joint fluid is a suitable method to obtain a representative specimen from the infection site. The puncture must be performed free of contamination, and microbiological processing must respect the special condition of these pathogens. For proof of infection in clinically doubtful cases, cytology of the joint fluid is useful. Aspiration of joint fluid is, apart from biopsy, one of the most important methods for detecting bacterial pathogens in periprosthetic infection. Cultural findings must be interpreted in the context of clinical, histomorphological, cytological, laboratory, and x-ray findings. If doubt remains, the diagnosis should be verified by repeated joint aspiration or by biopsy.

The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.

We analysed the serum C-reactive protein level, synovial fluid obtained by joint aspiration and five synovial biopsies from 145 knee replacements prior to revision to assess the value of these parameters in diagnosing late peri-prosthetic infection. Five further synovial biopsies were used for histological analysis. Samples were also obtained during the revision and incubated and analysed in an identical manner for 14 days. A total of 40 total knee replacements were found to be infected (prevalence 27.6%). The aspiration technique had a sensitivity of 72.5% (95% confidence interval (CI) 58.7 to 86.3), a specificity of 95.2% (95% CI 91.2 to 99.2), a positive predictive value of 85.3% (95% CI 73.4 to 100), a negative predictive value of 90.1% (95% CI 84.5 to 95.7) and an accuracy of 89%. The biopsy technique had a sensitivity of 100%, a specificity of 98.1% (95% CI 95.5 to 100), a positive predictive value of 95.2% (95% CI 88.8 to 100), a negative predictive value of 100% and an accuracy of 98.6%. C-reactive protein with a cut-off-point of 13.5 mg/l had a sensitivity of 72.5% (95% CI 58.7 to 86.3), a specificity of 80.9% (95% CI 73.4 to 88.4), a positive predictive value of 59.2% (95% CI 45.4 to 73.0), a negative predictive value of 88.5% (95% 81.0 to 96.0 CI) and an accuracy of 78.1%. We found that biopsy was superior to joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements.

[Consequence of European Directive 2004/23/EC for bone banks in Germany]. / Auswirkungen der EU-Geweberichtlinie 2004/23/EG auf deutsche Knochenbanken.

Allogenic bone grafting is an established method in revision surgery of artificial joint replacement and spinal surgery in case of bone defects. In Germany, femoral heads from living donors undergoing total hip replacement are frequently used. These grafts are processed according to the "Guidelines for the management of bone banking" issued by the Federal Medical Board. Bone grafts are drugs according to German law. Local bone banks are excluded from the regulations of the federal law on drugs [Arzneimittelgesetz (AMG) section sign 4a (4)] if certain requirements are fulfilled. The Directive 2004/23/EC of the European Parliament and of The Council on Setting Standards of Quality and Safety for the Donation, Procurement, Testing, Processing, Preservation, Storage and Distribution of Human Tissues and Cells has to be implemented into national law within 2 years. The exception of section sign 4a (4) will no longer be possible. Thus a legal construction has to be found which allows running local bone banks in compliance with the new legal settings. Three conditions will be possible: (1) a single physician procures a graft for another patient of his, (2) grafts are procured in one hospital and are used exclusively in this hospital: a license from the local authorities and a strict quality assessment according to GMP-rules is required, (3) if the grafts are distributed to other hospitals, a license from the local authorities and registration as a drug by the federal authorities are necessary.

[Inflammatory reactions in the wear particle induced and infectious periprosthetic membrane of loosened hip- and knee endoprostheses: pathogenetic relevance of differentially expressed genes cd9, cd11b, cd18, cd52 and pdgfrbeta]. / Inflammatorische Reaktion bei abriebinduzierter und infektiöser Lockerung von Hüft- und Knieendoprothesen.

BACKGROUND: A previous cDNA-microarray analysis described constantly differentially expressed genes in wear particle induced and infectious SLIM (synovial-like interface membrane). This study aims to validate the cDNA microarray data in order to approve differences of the gene expression profiles of RNA and proteins. METHODS: Tissue from 16 wear particle induced and 20 infectious periprosthetic membranes were analyzed by RT-PCR and immunohistology with regard to the expression of inflammatoric associated genes. RESULTS: RT-PCR showed the genes cd9, cd11b, cd18, cd52 as well as pdgfrbeta in interface membranes. In the wear particle induced membrane the immunohistochemical analysis showed a significantly weaker gene expression of PDGFRbeta, whereas the differential overexpression of CD9, CD11b and CD52 was confirmed. For CD18, there was no difference in expression between wear induced and infectious periprosthetic tissue. CONCLUSION: Different pathomechanisms, which are reflected by different gene expression profiles, might produce different types of periprosthetic membranes. By RT-PCR and immunohistochemical analysis the micro array data of the genes cd9, cd11b, cd52 and pdgfrbeta could be validated. Identifying the gene products of cd9, cd11b and cd52 in blood or tissue may help to differentiate between wear induced and infectious loosening.

[Guidelines on antimicrobial therapy in situations of periprosthetic THR infection]. / Prinzipien der Antibiotikabehandlung bei periprothetischen Infektionen.

Periprosthetic infection is nowadays a rare complication in artificial joint replacement. The infection of joint prostheses is a foreign body associated infection at the site of bone tissue which is difficult to treat with antimicrobial agents. Apart from cases with early, non-established infections, the surgical removal of the foreign material and radical débridement of bone and soft tissue is necessary. The surgical revision is performed preferentially using a one or two stage exchange of the prosthesis. In some cases, only the removal of the prosthesis is necessary. In these cases, a pseudoarthroplasty or an arthrodesis without definitely implanted foreign material is performed. Amputation is carried out if all other forms of revision have failed. All of these surgical procedures are accomplished by antimicrobial therapy, whether systemically administered and/or topically by drug delivery systems. Controlled studies for the comparison of one and two stage exchange procedures are not currently available. For the therapy of periprosthetic infection, an infectious disease specialist who is experienced in this area is needed in addition to an experienced surgical team. Thus, the therapy of these infections should be performed exclusively in centres of competence.

[Treatment of periprosthetic infection of the hip using one-stage exchange surgery]. / Behandlung der periprothetischen Infektion der Hüfte durch einzeitige Austauschoperation.

This article presents the theoretical microbiological principles involved in the pathogenesis of periprosthetic infection, the role of microbiology in diagnosing this disease, and factors requiring special consideration when selecting topical antibiotics. It also describes the operative technique of one-stage exchange arthroplasty using antibiotic-loaded acrylic cement and the results achieved with this method to date.

The efficacy of cefotaxime in gram-positive surgical infections.

In order to evaluate the efficacy of cefotaxime in gram-positive surgical infections, three clinical studies were re-evaluated. Antibiotic susceptibility tests were carried out on clinical isolates from our hospital during the period of clinical use of cefotaxime. The tissue fluid concentrations measured were compared to minimal inhibitory concentrations of gram-positive pathogens. Following 2 g cefotaxime i.v., tissue fluid concentrations were higher than 8 mg/l for more than 6 h and higher than 4 mg/l for more than 8 h. More than 90% of gram-positive pathogens excluding enterococci were inhibited at 4 mg/l. A comparison was made on the clinical efficacy of cefotaxime on infections caused by gram-positive organisms (group I) versus infections due to gram-negative bacteria (group II). 89 patients entered this study. In 40 patients only gram-positive bacteria were isolated initially (group I) and in 49 mainly gram-negative bacteria (group II). The mean age was 43 years (range 8-80 years) in group I and 61 years (range 19-92 years) in group II. Most patients received 2 g cefotaxime every 12 h. 40 skin and soft tissue infections (group I = 25, group II = 15), 25 pulmonary infections (group I = 7, group II = 18), 17 biliary infections (group I = 4, group II = 13) and nine bone and joint infections (group I = 4, group II = 5) were treated. The mean duration of therapy was nine (group I) and 11.2 (group II) days. Surprisingly, the cure rate was better in group I (70%) than in group II (59%).(ABSTRACT TRUNCATED AT 250 WORDS)

Emergence of related nontoxigenic Corynebacterium diphtheriae biotype mitis strains in Western Europe.

We report on 17 isolates of Corynebacterium diphtheriae biotype mitis with related ribotypes from Switzerland, Germany, and France. Isolates came from skin and subcutaneous infections of injecting drug users, homeless persons, prisoners, and elderly orthopedic patients with joint prostheses or primary joint infections. Such isolates had only been observed in Switzerland.