Diagnostic value of the CD 15 focus score in two-stage revision arthroplasty of periprosthetic joint infections : High specificity in diagnosing infect eradication.

INTRODUCTION: The purpose of this study is to use the CD15 focus score (FS) to determine the sensitivity and specificity of bacterial infection persistence in spacer-based two-stage revision arthroplasty. METHODS: The analysis comprises 112 cases that were subjected to revision due to the presence of infection upon replacement of a joint endoprosthesis. The histopathological data were collected in accordance with the synovial-like interface membrane (SLIM) classification and the CD15-FS and correlated with the microbiological data (MD). The quantifying evaluation of the CD15-FS was performed without knowledge regarding the microbiological data (MD). Correlation with the MD was performed after a 14-day cultivation period. RESULTS: With a single evaluation (1 focus, field area: 1.2 mm2) with a score value of 42, the CD15-FS showed a sensitivity for the eradication of infections of 0.64 and a specificity of 0.79 (PPV = 0.5; NPV = 0.87). With tenfold evaluation (10 foci, field area: 12 mm2) with a score value of 220, the sensitivity for the eradication was 0.68, the specificity 0.91 (PPV = 0.7; NPV = 0.89). No statistically significant correlation between the score values and the different infectious species could be detected. Based on the MD in 112 cases the rate of infection eradication was 75%. Polymethylmethacrylate-particles (PMMA) were detected in the perispacertissue in 64 cases (58%). No significant correlation could be established between microbiological pathogen detection and the presence of PMMA. CONCLUSION: In all cases (n = 112), periimplant synovial tissue (SLIM) with variable fibroblastic cellularity, capillary proliferation, leukocytic infiltration, fibrin deposition, new formation of woven bone and detection of PMMA particles was observed. These cases were classified as type IX perispacer synovialis/SLIM: type IX­A with histopathological infection eradication and type IX­B with histopathological infection persistence.

Bacteriophage therapy as a treatment strategy for orthopaedic-device-related infections: where do we stand?

Antibiotic resistance represents a key challenge of the 21st century. Since the pipeline of new antibiotics in development is limited, the introduction of alternative antimicrobial strategies is urgently required. Bacteriophage therapy, the use of bacterial viruses to selectively kill bacterial pathogens, is re-emerging as a potential strategy to tackle difficult-to-treat and multidrug-resistant pathogens. The last decade has seen a surge in scientific investigation into bacteriophage therapy, including targeting orthopaedic-device-related infections (ODRIs) in several successful case studies. However, pharmacological data, knowledge on the interplay with the immune system and, especially in ODRIs, the optimal local application strategy and treatment outcomes remain scarce. The present review reports the state-of-the-art in bacteriophage therapy in ODRIs and addresses the hurdles in establishing bacteriophage therapy under good clinical practice guidelines. These hurdles include a lack of data concerning bacteriophage production, processing, administration and dosing, as well as follow-up clinical monitoring reports. To overcome these challenges, an integrated clinical approach is required, supported by comprehensive legislature to enable expansive and correctly implemented clinical trials.

[Septic arthritis of the native joint and after ligamentoplasty : Diagnosis and treatment]. / Septische Arthritis des nativen Gelenkes und nach Bandplastik : Diagnostik und Behandlung.

BACKGROUND: Septic arthritis is an acute emergency. It occurs more frequently in patients with pre-existing degenerative or chronic inflammatory joint diseases than in the general population. The causative microorganisms can be introduced in various ways. DIAGNOSTICS: A rapid diagnosis is of great importance for the success of the therapy. In the clinical examination, the typical signs of inflammation are noticeable. The gold standard is the aspiration of synovial fluid and the subsequent laboratory and microbiological investigation. THERAPY: A prerequisite for successful therapy is the early initiation of an antimicrobial pathogen-specific treatment and the surgical alleviation of the joint.

[Risk factors and management strategies for early and late infections following reconstruction with special tumour endoprostheses]. / Risikofaktoren und Managementstrategien des Früh- und Spätinfektes nach Rekonstruktion mit Tumorspezialendoprothesen.

BACKGROUND: Periprosthetic joint infection (PJI) of megaprostheses occur in about 10% of all cases. The criteria for PJI are defined by the "Musculoskleletal Infection Society" (MSIS) and apply to both primary arthroplasty and megaprostheses. MANAGEMENT: The management strategies of PJI in megaprostheses are dependent on the duration of infection and the maturity of the bacterial biofilm. Implant retention with an exchange of the mobile components is only possible in the presence of an immature biofilm. In the presence of a mature biofilm, a one- or two-stage exchange must be performed. A complete exchange of all endoprosthetic components should be performed, if possible, since a partial retention of isolated components results in inferior treatment success rates. RESULTS: The highest success rates are achievable with two-stage exchanges. Multiple risk factors such as skin necrosis, postoperative haematoma, prolonged wound secretion and operative times ≥ 2.5 h are risk factors for the development of PJI in megaprostheses. Knowledge regarding these risk factors allows for an identification of high-risk patients and early management of PJI.

[Ulceroglandular tularemia after contact with a wild boar : Risk of infection for medical personnel by aerosol inhalation during lymph node resection]. / Ulzeroglanduläre Tularämie nach Kontakt mit Wildschwein : Infektionsrisiko für medizinisches Personal durch Inhalation von Aerosolen bei Lymphknotenresektion.

This article presents a case of ulceroglandular tularemia with local lymph node manifestation in a hobby hunter. An adequate diagnosis and early treatment of tularemia is of crucial importance not only for the patient, as when a surgical intervention is necessary there are also substantial risks for medical personnel. In the diagnosis of tularemia, which is rare but with an increasing incidence in Germany, the anamnesis provides the most important clues. A surgical intervention should only be performed after adequate treatment and duration of treatment.

Influence of retrieved hip- and knee-prosthesis biomaterials on microbial detection by sonication.

Microorganisms' ability to adhere and form a biofilm differs among biomaterials; however, clinical data are conflicting. Microbial adherence and biofilm formation on different biomaterials of explanted joint prosthesis components were investigated. Consecutive patients with explanted joint prosthesis were prospectively included. The bacterial load dislodged from retrieved prosthetic components was evaluated qualitatively and quantitatively in sonication-fluid cultures. For comparison between groups, one-way ANOVA and Wilcoxon signed-rank test were used. A total of 112 components originating from 58 knee and 54 hip prostheses were retrieved from 40 patients. Components were made of titanium alloy in 42 cases, cobalt-chromium alloy in 38 and polyethylene in 32. Bacteria in sonication-fluid cultures grew in all polyethylene components (100 %), followed by titanium alloy (79 %) and cobalt-chromium components (71 %). Larger bacterial counts were found on polyethylene than on titanium (p < 0.013) or cobalt-chromium alloy (p = 0.028). Coagulase-negative Staphylococcus aureus and Streptococcus species were most commonly isolated. In conclusion, polyethylene showed larger biofilm burden than metal alloys, indicating their higher microbial adhesion affinity in vivo. Sonication of polyethylene liners, rather than the whole prosthesis, was sufficient for diagnosis of prosthetic joint infection. Moreover, bacterial counts were larger after sonication of polyethylene liners than of metal alloys, suggesting intrinsic differences in the ability for biofilm formation on various biomaterials. Polyethylene liners allowed the diagnosis of prosthetic joint infections (PJIs) in all investigated cases, suggesting that sonication of polyethylene liners rather than of the complete prosthesis was sufficient for pathogen detection in PJIs.

[Beyond antibiotic therapy - Future antiinfective strategies - Update 2017]. / "Beyond antibiotic therapy" ­ Zukünftige antiinfektiöse Strategien ­ Update 2017.

BACKGROUND: The key elements in the therapy of surgical site infections (SSI) are surgical debridement and local and systemic antibiotic therapy; however, due to increasing antibiotic resistance, the development of additional therapeutic measures is of great interest for future trauma and orthopedic surgery. METHOD: Against the background of our own experimental and clinical experiences and on the basis of the current literature, possible future anti-infective strategies were elaborated. RESULTS/CONCLUSIONS: Bacteriophages were discovered and clinically implemented approximately one century ago and have been used in Western Europe for about one decade. They are currently used mainly in patients with burn injuries. It is likely that bacteriophages will become of great importance in view of the increasing antibiotic multi-drug resistance; however, they will probably not entirely replace antibiotic drugs. A combined use of bacteriophages and antibiotics is likely to be a more reasonable efficient therapy. In addition, the clinical importance of antimicrobial peptides (AMP) also increases. Up to now the possible use of AMPs is still experimental; however, individual AMPs are already established in the routine therapy (e. g. colistin). Further diagnostic and therapeutic measures may include photodynamic therapy, ultraviolet (UV) light application and differentiated genome analysis as well as the individual metabolism situation (metabolomics) of the pathogen cell and the patient tissue.

[Osteosynthesis-associated infections : Epidemiology, definition and diagnosis]. / Osteosyntheseassoziierte Infektionen : Epidemiologie, Definition und Diagnostik.

Osteosynthesis-associated infections occur in 1-5% after closed and in up to 30% after open fractures. There are three different descriptions of implant-associated infections after fracture fixation, which are crucial for the selection of the adequate treatment strategy; temporal appearance from the index surgery (early versus late), pathogenesis of the infection (exogenous, hematogenous and contiguous from an adjacent focus), duration of infection symptoms (acute versus chronic). Diagnosis of osteosynthesis-associated infection is challenging, as chronic low-grade infections often present only with unspecific and subtle clinical symptoms. History, clinical evaluation, imaging, histopathlogical and microbiological examination build the cornerstones of diagnostics in implant-associated infections. A new onset of rest pain, early loosening of the prosthesis or mechanically unexplained, nonunion should raise suspicion for infection and prompt further evaluation. Percutaneous sinus tracts, purulent wound secretion and skin erosions with visibility of the implant confirm the implant-associated infection. Elevated C­reactive protein value in blood is a supportive argument for infection, but is neither sensitive nor specific for infection. Imaging plays a key role to detect nonunions, infectious callus, sequester, peri-implant osteolysis and extraosseous and intramedullary involvement. Through microbiological and histopathological examination of intraoperative tissue samples, as well as sonication of explanted implants the causative pathogen is identified in most cases.

[Management of periprosthetic infections of the knee]. / Management periprothetischer Infektionen des Kniegelenks.

Endoprosthetic replacement is one of the most successful operations in current medicine. As the implantation of knee prostheses increases, the number of periprosthetic infections is also rising. In case of painful or early loosening of the prosthesis an infection should be excluded by joint aspiration. Retention of the prosthesis with change of mobile parts is possible only in acute infections (< 4 weeks after surgery or duration of symptoms of <3 weeks in the case of hematogenous infection), if the prosthesis is stable, the soft tissue is intact, and no difficult-to-treat pathogens were found. In other cases a one- or two-stage prosthesis exchange should be performed. In a two-stage exchange, a short interval of 2-3 weeks is possible, if biofilm-active treatment is available. Rifampin should be used targeted (after isolation of the pathogen) and only in combination with another efficient antibiotic. In this article the current management concepts of periprosthetic infection of the knee are discussed.

The potential use of microcalorimetry in rapid differentiation between septic arthritis and other causes of arthritis.

Current diagnostic methods in differentiating septic from non-septic arthritis are time-consuming (culture) or have limited sensitivity (Gram stain). Microcalorimetry is a novel method that can rapidly detect microorganisms by their heat production. We investigated the accuracy and time to detection of septic arthritis by using microcalorimetry. Patients older than 18 years of age with acute arthritis of native joints were prospectively included. Synovial fluid was aspirated and investigated by Gram stain, culture and microcalorimetry. The diagnosis of septic arthritis and non-septic arthritis were made by experienced rheumatologists or orthopaedic surgeons. Septic arthritis was diagnosed by considering the finding of acute arthritis together with findings such as positive Gram stain or positive culture of synovial fluid or positive blood culture. The sensitivity and specificity for diagnosing septic arthritis and the time to positivity of microcalorimetry were determined. Of 90 patients (mean age 64 years), nine had septic arthritis, of whom four (44 %) had positive Gram stain, six (67 %) positive synovial fluid culture and four (44 %) had positive blood culture. The sensitivity of microcalorimetry was 89 %, the specificity was 99 % and the mean detection time was 5.0 h (range, 2.2-8.0 h). Microcalorimetry is an accurate and rapid method for the diagnosis of septic arthritis. It has potential to be used in clinical practice in diagnosing septic arthritis.

Improved identification of polymicrobial infection in total knee arthroplasty through sonicate fluid cultures.

INTRODUCTION: Periprosthetic joint infection (PJI) is the leading cause for early failure of total knee arthroplasty (TKA). An insufficient diagnosis of the involved bacterial species can be a possible cause for this high failure rate. Sonicate fluid cultures (SFC) have been shown to increase the detection rate of PJI in comparison to the use of conventional microbiological methods. The hypothesis of this study is that sonication will improve not only the detection rate of PJI, but also the detection rate of polymicrobial infection in patients with TKA revision surgery. MATERIALS AND METHODS: 109 patients, undergoing TKA revision surgery, were enrolled in this prospective cohort study and received a synovial aspiration, intraoperative tissue cultures, histological sampling of the periprosthetic membrane (PM), and sonication of the explanted endoprosthesis. A PJI was defined according to the following criteria: presence of intraarticular pus or a sinus tract, positive isolation of the same bacterial species in ≥2 microbiological samples or a PM indicative of infection. RESULTS: 31 patients had a defined PJI according to the above-mentioned criteria. SFC achieved the highest sensitivity (74 %) of all microbiological methods. The PM achieved a sensitivity of 87 %. When the results of the SFC and the PM were combined, it was possible to further increase the sensitivity to 94 %. The utilization of SFC doubled the number of polymicrobial bacterial isolations in our patient collective. There were 12 cases of polymicrobial bacterial isolations, six were detectable through conventional microbiological methods, four were detectable through SFC and two were identifiable as polymicrobial through the isolation of an additional bacterial species in the SFC. CONCLUSIONS: In our study, SFC were the most sensitive microbiological method and were surpassed only by the histology. The use of SFC doubled the detection rate of polymicrobial isolations, which would be missed with conventional microbiological methods alone.

[Sonication in the diagnosis of periprosthetic infections : Significance and practical implementation]. / Sonikation in der Diagnostik periprothetischer Infektionen : Stellenwert und praktische Umsetzung.

Endoprosthetic joint replacement is one of the most common and most successful operations in current medicine. With the increase in joint prosthesis implantations, the number of periprosthetic infections is also rising. Detection of the causative pathogen and its antimicrobial susceptibility is crucial for successful antibiotic therapy. For a reliable diagnosis, in addition to conventional microbiological methods (synovial fluid culture and intraoperative periprosthetic tissue samples), other methods of detecting biofilms are used. With sonication of the removed implant components, microorganisms are released from the implant surface and then detected qualitatively and quantitatively in the sonication fluid. The sonication is particularly useful for chronic, "low-grade" infections in which a small number of bacteria are present and the biofilm adheres more strongly to the prosthesis surface. The sonication fluid is suitable for aerobic and anaerobic cultures, in addition to newer, culture-independent detection methods (e.g., molecular methods, mass spectrometry, microcalorimetry). In the article the significance, advantages and disadvantages, and the practical implementation of the sonication of implants are presented and critically discussed.

Influence of physico-chemical material characteristics on staphylococcal biofilm formation--a qualitative and quantitative in vitro analysis of five different calcium phosphate bone grafts.

Various compositions of synthetic calcium phosphates (CaP) have been proposed and their use has considerably increased over the past decades. Besides differences in physico-chemical properties, resorption and osseointegration, artificial CaP bone graft might differ in their resistance against biofilm formation. We investigated standardised cylinders of 5 different CaP bone grafts (cyclOS, chronOS (both ß-TCP (tricalcium phosphate)), dicalcium phosphate (DCP), calcium-deficient hydroxyapatite (CDHA) and α-TCP). Various physico-chemical characterisations e.g., geometrical density, porosity, and specific surface area were investigated. Biofilm formation was carried out in tryptic soy broth (TSB) and human serum (SE) using Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984). The amount of biofilm was analysed by an established protocol using sonication and microcalorimetry. Physico-chemical characterisation showed marked differences concerning macro- and micropore size, specific surface area and porosity accessible to bacteria between the 5 scaffolds. Biofilm formation was found on all scaffolds and was comparable for α-TCP, chronOS, CDHA and DCP at corresponding time points when the scaffolds were incubated with the same germ and/or growth media, but much lower for cyclOS. This is peculiar because cyclOS had an intermediate porosity, mean pore size, specific surface area, and porosity accessible to bacteria. Our results suggest that biofilm formation is not influenced by a single physico-chemical parameter alone but is a multi-step process influenced by several factors in parallel. Transfer from in vitro data to clinical situations is difficult; thus, advocating the use of cyclOS scaffolds over the four other CaP bone grafts in clinical situations with a high risk of infection cannot be clearly supported based on our data.

[Periprosthetic infection after hip arthroplasty]. / Periprothetische Infektion nach Hüftendoprothetik.

BACKGROUND: Periprosthetic infections (PPI) represent one of the most complex complications in arthroplasty concerning both, diagnosis and therapy. The incidence of PPI of the hip is approximately 1 % after primary procedures and 4 % after revision surgery. About two thirds of PPIs occur via intraoperative contamination and the remaining PPIs are acquired by hematogenous seeding. AIM: This article presents an overview of up to date evidence-based diagnostics and therapy of PPI of the hip with the establishment of a clear algorithm. METHODS: A selective literature search was carried out with the inclusion of own work. RESULTS: A PPI must be actively excluded in cases of a painful prosthesis or signs of loosening within the first years after implantation. Measurement of C-reactive protein (CRP) can be normal especially in cases of chronic (low grade) PPI and cannot be used as an exclusion criterion. The standard diagnostic procedure includes preoperative joint aspiration with culture and leukocyte counts as well as culture and histology of periprosthetic tissue. Imaging techniques, such as magnetic resonance imaging (MRI) and scintigraphy are of inferior significance. Newer methods, such as sonication of removed implants have revolutionized the diagnostics and several cases which had previously been considered aseptic loosening failures have now been reclassified as PPI. Essential parameters for the treatment algorithm are maturity of the biofilm, stability of the prosthesis, the causative organism and the state of the soft tissue. Retention of the prosthesis can only be considered when the biofilm is still immature (acute PPI). In chronic (low grade) PPI eradication of the infection can only be achieved by exchanging the prosthesis. This has to be performed either as a one-stage procedure or as a two-stage exchange with a short (2-4 weeks) or a long (> 6 weeks) interval. Biofilm active antibiotics play an essential role in the treatment of PPI and have to be used as targeted therapy. DISCUSSION: Successful therapy and diagnostics of PPI require following an exact algorithm. The interdisciplinary cooperation between specialists for infectious diseases and microbiologists represents a decisive factor.

[The "second life" of rifampicin]. / La deuxième vie de ta rifampicine.

Despite it was initially used and was restricted mainly for the treatment of tuberculosis, rifampicin gained in past years interest for the treatment of infections associated with prosthetic devices. Rifampicin has an excellent tissue penetration and a unique activity on bacteria in biofilms growing on the surface of prosthetic devices. The rapid emergence of resistance in bacteria constitutes the Achilles' heel and therefore rifampicin should be used with caution. This review addresses the mode of action of rifampicin and describes possible pitfalls of its use.

Bacterial biofilms and capsular contracture in patients with breast implants.

BACKGROUND: It has been hypothesized that bacterial biofilms on breast implants may cause chronic inflammation leading to capsular contracture. The association between bacterial biofilms of removed implants and capsular contracture was investigated. METHODS: Breast implants explanted between 2006 and 2010 at five participating centres for plastic and reconstructive surgery were investigated by sonication. Bacterial cultures derived from sonication were correlated with patient, surgical and implant characteristics, and the degree of capsular contracture. RESULTS: The study included 121 breast implants from 84 patients, of which 119 originated from women and two from men undergoing gender reassignment. Some 50 breast prostheses were implanted for reconstruction, 48 for aesthetic reasons and 23 implants were used as temporary expander devices. The median indwelling time was 4·0 (range 0·1-32) years for permanent implants and 3 (range 1-6) months for temporary devices. Excluding nine implants with clinical signs of infection, sonication cultures were positive in 40 (45 per cent) of 89 permanent implants and in 12 (52 per cent) of 23 temporary devices. Analysis of permanent implants showed that a positive bacterial culture after sonication correlated with the degree of capsular contracture: Baker I, two of 11 implants; Baker II, two of ten; Baker III, nine of 23; and Baker IV, 27 of 45 (P < 0·001). The most frequent organisms were Propionibacterium acnes (25 implants) and coagulase-negative staphylococci (21). CONCLUSION: Sonication cultures correlated with the degree of capsular contracture, indicating the potential causative role of bacterial biofilms in the pathogenesis of capsular contracture. REGISTRATION NUMBER: NCT01138891 (http://www.clinicaltrials.gov).

Biofilm formation by staphylococci on fresh, fresh-frozen and processed human and bovine bone grafts.

Biofilm formation is a multi-step process influenced by surface properties. We investigated early and mature biofilm of Staphylococcus aureus on 4 different biological calcium phosphate (CaP) bone grafts used for filling bone defects. We investigated standardised cylinders of fresh and fresh-frozen human bone grafts were harvested from femoral heads; processed humanand bovine bone grafts were obtained preformed. Biofilm formation was done in tryptic soy broth (TSB) using S. aureus (ATCC 29213) with static conditions. Biofilm density after 3 h (early biofilm) and 24 h (mature biofilm) was investigated by sonication and microcalorimetry. After 3 h, bacterial density was highest on fresh-frozenandfresh bone grafts. After 24 h, biofilm density was lowest on freshbone grafts (p < 0.001) compared to the other 3 materials, which did not differ quantitatively (p > 0.05). The lowest increase in bacterial density was detected on fresh bone grafts (p < 0.001). Despite normal shaped colonies, we found additional small colonies on the surface of the fresh and fresh-frozen samples by sonication. This was also apparent in microcalorimetric heat-flow curves. The four investigated CaP bone grafts showed minor structural differences in architecture but marked differences concerning serum coverage and the content of bone marrow, fibrous tissue and bone cells. These variations resulted in a decreased biofilm density on freshand fresh-frozenbone grafts after 24 h, despite an increased early biofilm formation and might also be responsible for the variations in colony morphology (small colonies). Detection of small colony variants by microcalorimetry might be a new approach to improve the understanding of biofilm formation.