Periprosthetic Joint Infection (PJI)-Results of One-Stage Revision with Antibiotic-Impregnated Cancellous Allograft Bone-A Retrospective Cohort Study.

Controversy exists regarding the optimal treatment of periprosthetic joint infection (PJI), considering control of infection, functional results as well as quality of life. Difficulties in treatment derive from the formation of biofilms within a few days after infection. Biofilms are tolerant to systemically applied antibiotics, requiring extreme concentrations for a prolonged period. Minimum biofilm eradicating concentrations (MBEC) are only feasible by the local application of antibiotics. One established approach is the use of allograft bone as a carrier, granting a sustained release of antibiotics in very high concentrations after appropriate impregnation. The purpose of this study was to determine the rate of reinfection after a one-stage revision of infected hip or knee prostheses, using antibiotic-impregnated allograft bone as the carrier and avoiding cement. Between 1 January 2004 and 31 January 2018, 87 patients with PJI, according to MSIS, underwent a one-stage revision with antibiotic-impregnated cancellous allograft bone. An amount of 17 patients had insufficient follow-ups. There were 70 remaining patients (34 male, 36 female) with a mean follow-up of 5.6 years (range 2-15.6) and with a mean age of 68.2 years (range 31.5-86.9). An amount of 38 hips and 11 knees were implanted without any cement; and 21 knees were implanted with moderate cementing at the articular surface with stems always being uncemented. Within 2 years after surgery, 6 out of 70 patients (8.6%, CI 2-15.1) showed reinfection and after more than 2 years, an additional 6 patients showed late-onset infection. Within 2 years after surgery, 11 out of 70 patients (15.7%, CI 7.2-24.2) had an implant failure for any reason (including infection) and after more than 2 years, an additional 7 patients had an implant failure. Using Kaplan-Meier analysis for all 87 patients, the estimated survival for reinfection was 93.9% (CI 88.8-99.1) at 1 year, 89.9% (CI 83.2-96.6) at 2 years and 81.5% (CI 72.1-90.9) at 5 years. The estimated survival for implant failure for any reason was 90.4% (CI 84.1-96.7) at 1 year, 80.9% (CI 72.2-89.7) at 2 years and 71.1% (CI 60.3-81.8) at 5 years. One-stage revision with antibiotic-impregnated cancellous allograft bone grants comparable results regarding infection control as with multiple stages, while shortening rehabilitation, improving quality of life for the patients and reducing costs for the health care system.

Metal Hypersensitivity or Missed Periprosthetic Joint Infection? A Critical Review.

The World Association Against Infection in Orthopedics And Trauma (W.A.I.O.T.) Study Group on Bone And Joint Infection Definitions Metal hypersensitivity (MHS) has been investigated by several authors as a possible reason for painful total joint arthroplasty, with controversial results. Periprosthetic joint infection (PJI) is another possible source of unexplained pain and implant failure that may be difficult to diagnose if not properly investigated. We performed this critical review to assess whether the current literature on MHS includes an adequate diagnostic workup to discern metal allergy from PJI. The results of this review highlight the importance of assessing patients for PJI before making a diagnosis of MHS and emphasize that the methods currently used to exclude PJI are substantially inadequate. Therefore, well-designed clinical trials with adequate diagnostic protocols and definitions of PJI that can differentiate MHS from low-grade PJI are needed. [Orthopedics. 2022;45(2):e73-e78.].

Influence of biofilm growth age, media, antibiotic concentration and exposure time on Staphylococcus aureus and Pseudomonas aeruginosa biofilm removal in vitro.

BACKGROUND: Biofilm is known to be tolerant towards antibiotics and difficult to eradicate. Numerous studies have reported minimum biofilm eradication concentration (MBEC) values of antibiotics for many known biofilm pathogens. However, the experimental parameters applied in these studies differ considerably, and often the rationale behind the experimental design are not well described. This makes it difficult to compare the findings. To demonstrate the importance of experimental parameters, we investigated the influence of biofilm growth age, antibiotic concentration and treatment duration, and growth media on biofilm eradication. Additionally, OSTEOmycin™, a clinically used antibiotic containing allograft bone product, was tested for antibiofilm efficacy. RESULTS: The commonly used Calgary biofilm device was used to grow 24 h and 72 h biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, which were treated with time-dependent vancomycin (up to 3000 mg L- 1) and concentration-dependent tobramycin (up to 80 mg L- 1), respectively. Two common bacteriological growth media, tryptic soy broth (TSB) and cation-adjusted Mueller Hinton broth (CaMHB), were tested. We found for both species that biofilms were more difficult to kill in TSB than in CaMHB. Furthermore, young biofilms (24 h) were easier to eradicate than old biofilms (72 h). In agreement with vancomycin being time-dependent, extension of the vancomycin exposure increased killing of S. aureus biofilms. Tobramycin treatment of 24 h P. aeruginosa biofilms was found concentration-dependent and time-independent, however, increasing killing was indicated for 72 h P. aeruginosa biofilms. Treatment with tobramycin containing OSTEOmycin T™ removed 72 h and 168 h P. aeruginosa biofilms after 1 day treatment, while few 72 h S. aureus biofilms survived after 2 days treatment with vancomycin containing OSTEOmycin V™. CONCLUSIONS: This study demonstrated biofilm removal efficacy was influenced by media, biofilm age and antibiotic concentration and treatment duration. It is therefore necessary to taking these parameters into consideration when designing experiments. The results of OSTEOmycin™ products indicated that simple in vitro biofilm test could be used for initial screening of antibiofilm products. For clinical application, a more clinically relevant biofilm model for the specific biofilm infection in question should be developed to guide the amount of antibiotics used for local antibiofilm treatment.

Diagnosis of peripheral bone and prosthetic joint infections: overview on the consensus documents by the EANM, EBJIS, and ESR (with ESCMID endorsement).

OBJECTIVES: Peripheral bone infection (PBI) and prosthetic joint infection (PJI) are two different infectious conditions of the musculoskeletal system. They have in common to be quite challenging to be diagnosed and no clear diagnostic flowchart has been established. Thus, a conjoined initiative on these two topics has been initiated by the European Society of Radiology (ESR), the European Association of Nuclear Medicine (EANM), the European Bone and Joint Infection Society (EBJIS), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). The purpose of this work is to provide an overview on the two consensus documents on PBI and PJI that originated by the conjoined work of the ESR, EANM, and EBJIS (with ESCMID endorsement). METHODS AND RESULTS: After literature search, a list of 18 statements for PBI and 25 statements for PJI were drafted in consensus on the most debated diagnostic challenges on these two topics, with emphasis on imaging. CONCLUSIONS: Overall, white blood cell scintigraphy and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities for the diagnosis of PBI and PJI. However, the choice of which advanced diagnostic modality to use first depends on several factors, such as the benefit for the patient, local experience of imaging specialists, costs, and availability. Since robust, comparative studies among most tests do not exist, the proposed flowcharts are based not only on existing literature but also on the opinion of multiple experts involved on these topics. KEY POINTS: • For peripheral bone infection and prosthetic joint infection, white blood cell and magnetic resonance imaging have individually demonstrated the highest diagnostic performance over other imaging modalities. • Two evidence- and expert-based diagnostic flowcharts involving variable combination of laboratory tests, biopsy methods, and radiological and nuclear medicine imaging modalities are proposed by a multi-society expert panel. • Clinical application of these flowcharts depends on several factors, such as the benefit for the patient, local experience, costs, and availability.

Correction to: Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

The authors regret to inform the readers that one of the author's name in the original publication of this article was spelled incorrectly as Victor Casar-Pullicino. The correct spelling is Victor N. Cassar-Pullicino and is now presented correctly in this article.

Consensus document for the diagnosis of prosthetic joint infections: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

BACKGROUND: For the diagnosis of prosthetic joint infection, real evidence-based guidelines to aid clinicians in choosing the most accurate diagnostic strategy are lacking. AIM AND METHODS: To address this need, we performed a multidisciplinary systematic review of relevant nuclear medicine, radiological, orthopaedic, infectious, and microbiological literature to define the diagnostic accuracy of each diagnostic technique and to address and provide evidence-based answers on uniform statements for each topic that was found to be important to develop a commonly agreed upon diagnostic flowchart. RESULTS AND CONCLUSION: The approach used to prepare this set of multidisciplinary guidelines was to define statements of interest and follow the procedure indicated by the Oxford Centre for Evidence-based Medicine (OCEBM).

Consensus document for the diagnosis of peripheral bone infection in adults: a joint paper by the EANM, EBJIS, and ESR (with ESCMID endorsement).

INTRODUCTION: In adults with a suspicion of peripheral bone infection, evidence-based guidelines in choosing the most accurate diagnostic strategy are lacking. AIM AND METHODS: To provide an evidence-based, multidisciplinary consensus document on the diagnostic management of adult patients with PBIs, we performed a systematic review of relevant infectious, microbiological, orthopedic, radiological, and nuclear medicine literature. Delegates from four European societies (European Bone and Joint Infection Society, European Society of Microbiology and Infectious Diseases, European Society or Radiology, and European Association of Nuclear Medicine) defined clinical questions to be addressed, thoroughly reviewed the literature pertinent to each of the questions, and thereby evaluated the diagnostic accuracy of each diagnostic technique. Inclusion of the papers per statement was based on a PICO (Population/problem - Intervention/indicator - Comparator - Outcome) question following the strategy reported by the Oxford Centre for Evidence-based Medicine. For each statement, the level of evidence was graded according to the 2011 review of the Oxford Centre for Evidence-based Medicine. All approved statements were addressed taking into consideration the available diagnostic procedures, patient acceptance, tolerability, complications, and costs in Europe. Finally, a commonly agreed-upon diagnostic flowchart was developed.

Treatment of chronic orthopaedic infection.

Chronic infections are one of the major challenges in orthopaedic surgery, both for surgeons and patients. They are characterised by obstinate persistency of the causing microorganisms and resulting long-term disablement of the patients, associated with remarkable costs for the health care system.Difficulties derive from the biofilm-mode of living of pathogens with resistances against immunological defence and antimicrobial substances, and osseous defects resulting from the disease itself and surgical interventions.Established techniques usually require multiple costly operations with extended periods of disablement and impairment of the patients, sometimes making the therapy worse than the disease.Better understanding of the backgrounds of the conditions has led to new surgical techniques and differentiated application of antibiotics, aiming in improved quality of life for our patients. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160063. Originally published online at www.efortopenreviews.org.

Local Antimicrobial Treatment in Orthopaedic Surgery.

The purpose of this special issue of Journal of Bone and Joint Infection is to provide orthopaedic surgeons with basic science explanations as to how these local antimicrobials work, clinical evidence that supports these local treatments, and the role of these local treatments against biofilm.

Allograft Bone as Antibiotic Carrier.

The treatment of chronic bone and joint infections is characterized by obstinate persistency of the causing microorganisms and resulting long term disability to patients, associated with remarkable costs for the health care system. Difficulties derive from biofilm formed on dead bone and eventual implants, with resistance against immunological defences and antimicrobial substances. Biofilm embedded bacteria require up to 1000 times the antibiotic concentration of planktonic bacteria for elimination. Systemic antibiotic treatment alone cannot provide the concentrations required and surgical intervention is always prerequisite for potentially providing a cure. A second issue is that osseous defects are almost always present after surgical debridement, and it is difficult to address their reconstruction. One option is to use bone grafts, either from the patient´s own body or from foreign donors (allografts). Grafts are usually unvascularized and are prone to colonization with bacteria. Loading of allografts with antibiotics may not only protect grafts from bacterial adhesion but, using appropriate processing methods, may also provide high local antibiotic concentrations that may eliminate remaining sessile pathogens. For efficient action as antibiotic carriers, the release of antibiotics should be above the minimum biofilm eradication concentration (MBEC) for a prolonged period of time. Cleaning the bone from bone marrow opens a large reservoir for storage of antimicrobial substances that, after implantation, may be released to the surrounding in a sustained mode, possibly eliminating remaining biofilm remnants. Removal of bone marrow, leaving a pure matrix, provides increased safety and improved revascularization of the graft. Local provision of antibiotic concentrations above the MBEC may enable simultaneous internal fixation with osteosynthetic material and single stage exchange of infected endoprostheses, resulting in shorter hospital stays with reduced pain and faster rehabilitation of patients.

Bone grafting and one-stage revision of THR - biological reconstruction and effective antimicrobial treatment using antibiotic impregnated allograft bone.

Infection of a total hip replacement (THR) is considered one of the most serious complications in orthopaedic surgery. Problems derive from the presence of biofilms with inherent resistance to usual antibiotic treatment and bone defects resulting from infection induced osteolysis. Discussions on the choice of treatment mainly focus on the chance of eradicating the infection in either one or more stages. The advantages of only one operation with regard to patients' satisfaction, functional results and economical burden are evident. However, the fear of re-infection usually leads surgeons to multiple stage procedures, mostly using antibiotic loaded spacers in the interval. Spacers have no effect on biofilms and are associated with a high rate of complications such as breakage or dislocation. Cemented revisions show several disadvantages like reduction of biomechanical properties through added antibiotics, inferior long term results, difficulties of removal in case of recurrence etc. Uncemented implants appear more advantageous but are at risk of becoming colonised by remaining biofilm fragments. To overcome this risk higher local concentrations of antibiotics are needed. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques, resulting in an antibiotic bone compound (ABC). ABC provides local concentrations exceeding those of cement by more than a 100-fold and efficient release is prolonged for several weeks. At the same time it is likely to restore bone stock, which is usually compromised after removal of an infected endoprosthesis. Based on these considerations new protocols for one-stage exchange of infected THR have been established. Bone voids may be filled with ABC, uncemented implants may be fixed in original healthy bone. Recent studies indicate an overall success rate of more than 90% with one operation, without any adverse side effects. Incorporation of allografts appears as after grafting with unimpregnated bone grafts. One stage revision using ABC together with uncemented implants, should be at least comparable to multiple stage procedures, but with the advantage of the obvious benefits for patients and cost.

Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft.

Infection of a total hip replacement (THR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. It is undoubted that one stage exchange, if successful, would provide the best benefit both for the patient and the society. Still the fear of re-infection dominates the surgeons decisions and in the majority of cases directs them to multiple stage protocols. However, there is no scientifically based argument for that practice. Successful eradication of infection with two stage procedures is reported to average 80% to 98%. On the other hand a literature review of Jackson and Schmalzried (CORR 2000) summarizing the results of 1,299 infected hip replacements treated with direct exchange (almost exclusively using antibiotic loaded cement), reports of 1,077 (83%) having been successful. The comparable results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of surgical debridement and dead space management. Failures in all protocols seem to be caused by small fragments of bacterial colonies remaining after debridement, whereas neither systemic antibiotics nor antibiotic loaded bone cement (PMMA) have been able to improve the situation significantly. Reasons for failure may be found in the limited sensitivity of traditional bacterial culturing and reduced antibiotic susceptibility of involved pathogens, especially considering biofilm formation. Whenever a new prosthesis is implanted into a previously infected site the surgeon must be aware of increased risk of failure, both in single or two stage revisions. Eventual removal therefore should be easy with low risk of additional damage to the bony substance. On the other hand it should also have potential of a good long term result in case of success. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its biomechanical properties. Efficient cementing techniques will result in tight bonding with the underlying bone, making eventual removal time consuming and possibly associated with further damage to the osseous structures. All these issues are likely to make uncemented revisions more desirable. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques. The storage capacities and pharmacological kinetics of the resulting antibiotic bone compound (ABC) are more advantageous than the ones of antibiotic loaded cement. ABC provides local concentrations exceeding those of cement by more than a 100fold and efficient release is prolonged for several weeks. The same time they are likely to restore bone stock, which usually is compromised after removal of an infected endoprosthesis. ABC may be combined with uncemented implants for improved long term results and easy removal in case of a failure. Specifications of appropriate designs are outlined. Based on these considerations new protocols for one stage exchange of infected TJR have been established. Bone voids surrounding the implants may be filled with antibiotic impregnated bone graft; uncemented implants may be fixed in original bone. Recent studies indicate an overall success rate of more than 90% without any adverse side effects. Incorporation of allografts appears as after grafting with unimpregnated bone grafts. Antibiotic loaded bone graft seems to provide sufficient local antibiosis for protection against colonisation of uncemented implants, the eluted amounts of antibiotics are likely to eliminate biofilm remnants, dead space management is more complete and defects may be reconstructed efficiently. Uncemented implants provide improved long term results in case of success and facilitated re-revision in case of failure. One stage revision using ABC together with uncemented implants such should be at least comparably save as multiple stage procedures, taking advantage of the obvious benefits for patients and economy.

Bone grafts impregnated with antibiotics as a tool for treating infected implants in orthopedic surgery - one stage revision results.

Infection of an orthopedic implant is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. Osseous defects are common in such conditions and need to be addressed before a new implant may be inserted. So far bone grafting has been contraindicated in bacterially contaminated areas and could only be performed as soon as all signs of infection have ceased. Usually long term antibiotic treatment and a multitude of surgical interventions within a period of several months is required until a definitive supply can be achieved. Allograft bone may be impregnated with high loads of antibiotics using special incubation techniques. Based on this technology 48 exchange procedures of infected orthopaedic implants were performed in a single stage, all of them without the use of bone cement. There were 37 infected hips, 8 knees and 3 infected osteosyntheses. Two hips required re-revision because of persisting infection, the remaining 46 patients stayed infect free for a period between 1 and 7 years after surgery. No adverse side effects could be found. Incorporation appeared as after grafting with unimpregnated bone grafts. Antibiotic loaded allograft bone is a powerful tool in septic revision surgery, enabling restoration of bone stock, insertion of a new implant and control of infection in a single operation.

Structural behavior of nanometric carbohydrate films transduced by a resonant technique.

New optical nanoresonance effects enabled us to study the effect of ions on nanometric carbohydrate thin layers on chips. Immobilization was done via spin coating of the derivatized carbohydrate polymer at a metallized chip surface forming ultrathin films (about 50-300 nm thick) followed by photochemical cross-linking. Deposition of metal-nanoclusters, synthesized by chemical means and sputter coating on top of the polymer, induced an optical resonance effect, which transduced changes of polymer structure quantitatively into an optical signal that can be observed directly as resonance shift of a narrow optical peak. The response of the sensor chip even visible to the eye was quantified spectroscopically in the visible and ir range of the spectrum. The lifetime of thin film was good, and thus application as a sensor was limited only by the mechanical stability of the reactive matrix, but not by photobleaching or molecular leakage. Due to the inherent hydrophilic nature of the alginate polymer, the response time of this new sensor is governed by simple aqueous diffusion of the ionic calcium for up to 300 nm completed within less than one second. Monitoring of calcium fluctuations in a high background of magnesium and even serum was demonstrated with a dynamic range optimal for physiological measurements and a linear response up to 5 mM. Surface and alignment of polymer chain were influenced by the nanostructure of the supporting metal film-contrary to alginic acid, chitosan was deposited well aligned to the nanocrystals of the support.