D-lactate is a promising biomarker for the diagnosis of periprosthetic joint infection.

Introduction: Reliable biomarkers for the diagnosis of periprosthetic joint infection (PJI) are of paramount clinical value. To date, synovial fluid leukocyte count is the standard surrogate parameter indicating PJI. As D-lactate is almost solely produced by bacteria, it represents a promising molecule in the diagnostic workflow of PJI evaluation. Therefore, the purpose of this study was to assess the performance of synovial fluid D-lactate for diagnosing PJI of the hip and knee. Materials and Methods: These are preliminary results of a prospective multicenter study from one academic center. Seventy-two consecutive patients after total hip arthroplasty (THA) or total knee arthroplasty (TKA) were prospectively included. All patients received a joint aspiration in order to rule out or confirm PJI, which was diagnosed according to previously published institutional criteria. Synovial fluid D-lactate was determined spectrophotometrically at 450 nm. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. Results: Eighteen patients (25%) were diagnosed with PJI and 54 patients (75%) were classified as aseptic. Synovial fluid D-lactate showed a sensitivity of 90.7% (95% CI: 79.7%-96.9%) and specificity of 83.3% (95% CI: 58.6%-96.4%) at a cut-off of 0.04 mmol/L. The median concentration of D-lactate was significantly higher in patients with PJI than in those with aseptic conditions (0.048 mmol/L, range, 0.026-0.076 mmol/L vs. 0.024 mmol/L, range, 0.003-0.058 mmol/L, p < 0.0001). The predominat microogranisms were staphylococci, followed by streptococci and gram-negative bacteria. Conclusion: D-lactate bears a strong potential to act as a valuable biomarker for diagnosing PJI of the hip and knee. In our study, a cutoff of 0.04 mmol/L showed a comparable sensitivity to synovial fluid leukocyte count. However, its specificity was higher compared to conventional diagnostic tools. The additional advantages of D-lactate testing are requirement of low synovial fluid volume, short turnaround time and low cost.

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.

[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.

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.

[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.

[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.

Pathogenesis and management of fracture-related infection.

BACKGROUND: Both fracture-related infections (FRIs) and periprosthetic joint infections (PJIs) include orthopaedic implant-associated infections. However, key aspects of management differ due to the bone and soft tissue damage in FRIs and the option of removing the implant after fracture healing. In contrast to PJIs, research and guidelines for diagnosis and treatment in FRIs are scarce. OBJECTIVES: This narrative review aims to update clinical microbiologists, infectious disease specialists and surgeons on the management of FRIs. SOURCES: A computerized search of PubMed was performed to identify relevant studies. Search terms included 'Fracture' and 'Infection'. The reference lists of all retrieved articles were checked for additional relevant references. In addition, when scientific evidence was lacking, recommendations are based on expert opinion. CONTENT: Pathogenesis, prevention, diagnosis and treatment of FRIs are presented. Whenever available, specific data of patients with FRI are discussed. IMPLICATIONS: Management of patients with FRI should take into account FRI-specific features. Treatment pathways should implement a multidisciplinary approach to achieve a good outcome. Recently, international consensus guidelines were developed to improve the quality of care for patients suffering from this severe complication, which are highlighted in this review.

A standardized interdisciplinary algorithm for the treatment of prosthetic joint infections.

AIMS: In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach. PATIENTS AND METHODS: In a retrospective analysis with a standard postoperative follow-up, 95 patients with a PJI of the hip and knee who were treated with a two-stage exchange between 2013 and 2017 formed the study group. A historical cohort of 86 patients treated between 2009 and 2011 not according to the standardized protocol served as a control group. The success of treatment was defined according to the Delphi criteria in a two-year follow-up. RESULTS: Patients in the study group had a significantly higher Charlson Comorbidity Index (3.9 vs 3.1; p = 0.009) and rate of previous revisions for infection (52.6% vs 36%; p = 0.025), and tended to be older (69.0 vs 66.2 years; p = 0.075) with a broader polymicrobial spectrum (47.3% vs 33.7%; p = 0.062). The rate of recurrent infection (3.1% vs 10.4%; p = 0.048) and the mean time interval between the two stages of the procedure (66.6 vs 80.7 days; p < 0.001) were reduced significantly in the study group compared with the control group. CONCLUSION: We were able to show that the outcome following the treatment of PJIs of the hip and knee is better when managed in a separate department with an interdisciplinary team using a standard algorithm.

Origin and characteristics of haematogenous periprosthetic joint infection.

OBJECTIVES: Recognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI. METHODS: Consecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and Mann-Whitney U tests were used, as appropriate. RESULTS: A total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1-417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n = 43), streptococci (n = 32), enterococci (n = 13), Gram-negative bacteria (n = 9) and coagulase-negative staphylococci (n = 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes). CONCLUSIONS: In acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.

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.

High failure rates in treatment of streptococcal periprosthetic joint infection: results from a seven-year retrospective cohort study.

AIMS: To investigate the outcomes of treatment of streptococcal periprosthetic joint infection (PJI) involving total knee and hip arthroplasties. PATIENTS AND METHODS: Streptococcal PJI episodes which occurred between January 2009 and December 2015 were identified from clinical databases. Presentation and clinical outcomes for 30 streptococcal PJIs in 30 patients (12 hip and 18 knee arthroplasties) following treatment were evaluated from the medical notes and at review. The Kaplan-Meier survival method was used to estimate the probability of infection-free survival. The influence of the biofilm active antibiotic rifampin was also assessed. RESULTS: The infection was thought to have been acquired haematogenously in 16 patients and peri-operatively in 14. The median follow-up time for successfully treated cases was 39.2 months (12 to 75), whereas failure of the treatment occurred within the first year following treatment on every occasion. The infection-free survival at three years with 12 patients at risk was 59% (95% confidence interval 39% to 75%). Failure of the treatment was observed in ten of 22 PJIs (45%) treated with a two-stage revision arthroplasty, two of six (33%) treated by debridement and prosthesis retention, and in neither of the two PJIs treated with one-stage revision arthroplasty. Streptococcal PJI treated with or without rifampin included in the antibiotic regime showed no difference in treatment outcome (p = 0.175). CONCLUSION: The success of treatment of streptococcal PJI in our patient cohort was poor (18 of 30 cases, 59%). New therapeutic approaches for treating streptococcal PJI are needed. Cite this article: Bone Joint J 2017;99-B:653-9.

CD15 focus score: Infection diagnosis and stratification into low-virulence and high-virulence microbial pathogens in periprosthetic joint infection.

INTRODUCTION: The aim of the work was to validate the CD15 focus score for the infection pathology of periprosthetic joint infection in a large group and to clarify whether a stratification into low-virulence and high-virulence microbial pathogens is possible by means of the CD15 focus score (quantification of CD15 positive granulocytes). METHODS: The histopathology of 275 synovial tissue samples taken intraoperatively during revision operations (n=127 hip, n=141 knee, n=2 shoulder, n=5 ankle) was evaluated according to the SLIM consensus classification (SLIM=synovial-like interface membrane). Neutrophilic granulocytes (NG) were quantified by the CD15 focus score on the basis of the principle of focal maximum infiltration (focus) with evaluation of one field of vision (about 0.3mm2). The quantification values were compared with the microbiological diagnoses taking into consideration the virulence groups of low-virulence and high-virulence microbial pathogens and mixed infection. RESULTS: The patients with positive microbiological findings (n=160) had significantly (p<0.001, Mann-Whitney U test) higher CD15 focus score values than patients with negative microbiological findings (n=115), the cut-off value being 39 cells per high power field (HPF). The CD15 focus score values of low-virulence microbial pathogens (n=94) were significantly lower (p<0.001, Mann-Whitney U test) than the values of high-virulence microbial pathogens (n=55), the cut-off value being 106 cells per HPF. Based on the microbiological diagnosis the sensitivity with respect to a microbial infection is 0.91, the specificity 0.92 (PPV=0.94; NPV=0.88; accuracy: 0.92; AUC=0.95). Based on the differentiation of the CD15 focus score values between low-virulence and high-virulence microbes the sensitivity is 0.70 and the specificity 0.77 (PPV=0.63; NPV=0.81; accuracy=0.74; AUC=0.74). CONCLUSION: As a result of the high sensitivity and specificity, the easy to use CD15 focus score is a diagnostically valid score for microbial periprosthetic infection. A differentiation between low-virulence and high-virulence microorganism of sufficiently high diagnostic quality is additionally possible as a result of the defined quantification of CD15 positive granulocytes (the CD15 focus score) histopathological diagnosis of microbial infections is possible, which on the one hand supports the microbiological diagnosis and on the other hand by the stratification into low-virulence and high-virulence microbial pathogens could represent an additional basis for a pathogen-specific antibiotic treatment in the event of unclear constellations of findings.

[Treatment of periprosthetic infections]. / Therapie der periprothetischen Infektion.

The increasing number of prosthesis implantations and higher life expectancy lead to a growing number of periprosthetic infections (PPI). Optimal therapy necessitates interdisciplinary coordination of surgical and antimicrobial treatment. Challenges in the treatment are the increased occurrence of resistant pathogens, selection of adequate antimicrobial and surgical treatment strategies, inappropriate pretreatment and comorbidities of patients. Current treatment concepts lead to a high success rate in terms of infection eradication, when correctly applied. The individual expectations and underlying conditions of each patient must be considered when determining the therapy concept. The first step is to distinguish between acute and chronic infections. In acute infections the prosthesis can be retained but chronic infections necessitate a complete exchange of the prosthesis. Complicating factors, such as compromising soft tissue and bone conditions, osteomyelitis and infections caused by difficult-to-treat bacteria should, however, always be treated by a complete exchange of the prosthesis, even for acute infections. The antimicrobial treatment must be tailored to the causative agent, the surgical strategy as well as comorbidities and drug intolerances of the patient. It is important to distinguish between biofilm-active eradication therapy with rifampicin for gram-positive pathogens and quinolones for gram-negative organisms and suppression therapy. This article gives a structured presentation of the therapy algorithm.

[Implant-associated infections - Diagnostics]. / Implantatassoziierte Infektion - Diagnostik.

The diagnosis of implant-associated infections is challenging as chronic low-grade infections often only manifest as subtle clinical symptoms. Clinical evaluation, patient history, imaging, histopathological and microbiological examinations build the cornerstones of the diagnostics for implant-associated infections. New onset of pain at rest, local symptoms at the surgical site and early loosening of the prosthesis or pseudarthrosis should raise suspicion for an infection and prompt further evaluation. Percutaneous sinus tracts, purulent wound secretions and skin erosions with exposure of the implant are certain signs of implant-associated infections. Elevated C­reactive protein levels in blood support the diagnosis of infection but are neither sufficient sensitive nor specific to confirm or exclude infection. Preoperative antibiotic therapy interferes with the diagnostic evaluation and should be avoided. In periprosthetic joint infections, joint aspiration with determination of the leukocyte count and microbiological examination is a crucial first diagnostic step. Through microbiological and histopathological examinations of intraoperative tissue samples, as well as sonication of explanted implants, the causative pathogen can be identified in most cases. In osteosynthesis-associated infections imaging plays a key role to detect non-union, infection callus, sequester, peri-implant osteolysis and extraosseous and intramedullary pathologies. In prosthetic joint infections imaging provides information about the position and stability of the prosthesis. In case of hematogenic infection seeding from a distant focus, blood cultures should be sampled, followed by a meticulous investigation of potential primary focus of infection, depending on the causative agent.