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Purpose: Staphylococcus aureus is the most common and impactful multi-drug resistant pathogen implicated in (periprosthetic) joint infections (PJI) and fracture-related infections (FRI). Therefore, the present proof-of-principle study was aimed at the rapid detection of S. aureus in synovial fluids and biofilms on extracted osteosynthesis materials through bacteria-targeted fluorescence imaging with the 'smart-activatable' DNA-based AttoPolyT probe. This fluorogenic oligonucleotide probe yields large fluorescence increases upon cleavage by micrococcal nuclease, an enzyme secreted by S. aureus., Methods: Synovial fluids from patients with suspected PJI and extracted osteosynthesis materials from trauma patients with suspected FRI were inspected for S. aureus nuclease activity with the AttoPolyT probe. Biofilms on osteosynthesis materials were imaged with the AttoPolyT probe and a vancomycin-IRDye800CW conjugate (vanco-800CW) specific for Gram-positive bacteria., Results: 38 synovial fluid samples were collected and analyzed. Significantly higher fluorescence levels were measured for S. aureus-positive samples compared to, respectively, other Gram-positive bacterial pathogens (p < 0.0001), Gram-negative bacterial pathogens (p = 0.0038) and non-infected samples (p = 0.0030), allowing a diagnosis of S. aureus-associated PJI within 2 h. Importantly, S. aureus-associated biofilms on extracted osteosynthesis materials from patients with FRI were accurately imaged with the AttoPolyT probe, allowing their correct distinction from biofilms formed by other Gram-positive bacteria detected with vanco-800CW within 15 min., Conclusion: The present study highlights the potential clinical value of the AttoPolyT probe for fast and accurate detection of S. aureus infection in synovial fluids and biofilms on extracted osteosynthesis materials., (© 2023. The Author(s).)

Purpose: Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints., Methods: Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses., Results: We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW., Conclusion: The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection.

Aims: It is essential to exclude a periprosthetic joint infection (PJI) prior to revision surgery. It is recommended to routinely aspirate the joint before surgery. However, this may not be necessary in a subgroup of patients. The aim of our study was to investigate if specific clinical and implant characteristics could be identified to rule out a PJI prior to revision surgery., Methods: We retrospectively evaluated clinical and implant characteristics of patients who underwent a hip or knee revision surgery between October 2015 and October 2018. Patients were diagnosed with a PJI according to the MSIS diagnostic criteria., Results: A total of 156 patients were analyzed, including 107 implants that were revised because of prosthetic loosening and 49 because of mechanical failure (i.e. instability, malalignment or malpositioning). No PJI was diagnosed in the group with mechanical failure. In the prosthetic loosening group, 20 of 107 were diagnosed with a PJI (19%). Although there was a significantly lower chance of having a PJI with an implant age of > 5 years combined with a CRP < 5 mg/L, an infection was still present in 3 out of 39 cases (8%)., Conclusion: Implants with solely mechanical failure without signs of loosening and low inflammatory parameters probably do not require a synovial fluid aspiration. These results need to be confirmed in a larger cohort of patients. In case of prosthetic loosening, all joints need to be aspirated before surgery as no specific characteristic could be identified to rule out an infection.

Introduction: A prolonged incubation time is generally recommended for diagnosing periprosthetic joint infections (PJI). However, in literature, no distinction is made between acute and chronic infections., Methods: All patients with a PJI that underwent surgical debridement between November 2015 and February 2019 with or without revision of the prosthesis were retrospectively evaluated. Synovial fluid, 5 intraoperative periprosthetic tissue samples, and the sonicated prosthesis were cultured., Results: Fifty-nine patients were analyzed, including 21 acute PJIs (33 isolates) and 38 chronic PJIs (46 isolates). In acute PJIs, all isolates grew within 5 days, while this took 11 days for chronic PJIs. Sonication fluid showed the shortest time to positivity (78% at day 2) for chronic PJIs, but no difference was observed for acute PJIs compared to tissue cultures., Conclusion: In contrast to cultures from chronic PJIs, acute PJIs do not need a prolonged incubation time and no clear benefit is observed for sonication., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In acute periprosthetic joint infections (PJIs), a second surgical debridement (debridement, antibiotics, and implant retention [DAIR]) is generally not recommended after a failed first one. We identified the failure rate of a second DAIR and aimed to identify patients in whom an additional debridement might still be beneficial., Methods: Patients with acute PJI of the hip or knee and treated with DAIR between 2006 and 2016 were retrospectively evaluated. A second DAIR was routinely performed provided that the soft tissue was intact. Failure of a second DAIR was described as (1) the need for additional surgical intervention to achieve infection control, (2) the need for antibiotic suppressive therapy due to persistent clinical and/or biochemical signs of infection, or (3) PJI related death., Results: From the 455 cases treated with DAIR, 144 cases underwent a second debridement (34.6%). Thirty-seven cases failed (37/144, 25.7%). The implant needed to be removed in 23 cases (23/144, 16%). Positive cultures during the second DAIR (odds ratio 3.16, 95% confidence interval 1.29-7.74) and chronic renal insufficiency (odds ratio 13.6, 95% confidence interval 2.03-91.33) were independent predictors for failure in the multivariate analysis. No difference in failure was observed between persistent infection with the same microorganism and reinfection with a new microorganism (failure rate 31.6% vs 34.6%, P = .83)., Conclusion: A second DAIR had a low failure rate in our cohort of patients and the implant could be retained in the majority of them. Therefore, a second DAIR should not be discarded in acute PJIs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The success of debridement, antibiotics, and implant retention (DAIR) in early periprosthetic joint infection (PJI) largely depends on the presence of a mature biofilm. At what time point DAIR should be disrecommended is unknown. This multicenter study evaluated the outcome of DAIR in relation to the time after index arthroplasty., Methods: We retrospectively evaluated PJIs occurring within 90 days after surgery and treated with DAIR. Patients with bacteremia, arthroscopic debridements, and a follow-up <1 year were excluded. Treatment failure was defined as (1) any further surgical procedure related to infection; (2) PJI-related death; or (3) use of long-term suppressive antibiotics., Results: We included 769 patients. Treatment failure occurred in 294 patients (38%) and was similar between time intervals from index arthroplasty to DAIR: the failure rate for Week 1-2 was 42% (95/226), the rate for Week 3-4 was 38% (143/378), the rate for Week 5-6 was 29% (29/100), and the rate for Week 7-12 was 42% (27/65). An exchange of modular components was performed to a lesser extent in the early post-surgical course compared with the late course (41% vs 63%, respectively; P < .001). The causative microorganisms, comorbidities, and durations of symptoms were comparable between time intervals., Conclusions: DAIR is a viable option in patients with early PJI presenting more than 4 weeks after index surgery, as long as DAIR is performed within at least 1 week after the onset of symptoms and modular components can be exchanged., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

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.

Background: Obese patients are more likely to develop periprosthetic joint infection (PJI) after primary total joint arthroplasty. This study compared the clinical and microbiological characteristics of non-obese, obese and severely obese patients with early PJI, in order to ultimately optimize antibiotic prophylaxis and other prevention measures for this specific patient category., Methods: We retrospectively evaluated patients with early PJI of the hip and knee treated with debridement, antibiotics and implant retention (DAIR) between 2006 and 2016 in three Dutch hospitals. Only patients with primary arthroplasties indicated for osteoarthritis were included. Early PJI was defined as an infection that developed within 90 days after index surgery. Obesity was defined as a BMI ≥30kg/m2 and severe obesity as a BMI ≥35kg/m2., Results: A total of 237 patients were analyzed, including 64 obese patients (27.0%) and 62 severely obese patients (26.2%). Compared with non-obese patients, obese patients had higher rates of polymicrobial infections (60.3% vs 33.3%, p<0.001) with more often involvement of Enterococcus species (27.0% vs 11.7%, p = 0.003). Moreover, severely obese patients had more Gram-negative infections, especially with Proteus species (12.9% vs 2.3%, p = 0.001). These results were only found in periprosthetic hip infections, comprising Gram-negative PJIs in 34.2% of severely obese patients compared with 24.7% in obese patients and 12.7% in non-obese patients (p = 0.018)., Conclusions: Our results demonstrate that obese patients with early periprosthetic hip infections have higher rates of polymicrobial infections with enterococci and Gram-negative rods, which stresses the importance of improving preventive strategies in this specific patient category, by adjusting antibiotic prophylaxis regimens, improving disinfection strategies and optimizing postoperative wound care., Competing Interests: The authors have declared that no competing interests exist.

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).

Background: Persistent wound drainage after total joint arthroplasty (TJA) is an important complication with potential substantial adverse consequences, in particular periprosthetic joint infection., Methods: This review evaluated the available literature regarding several issues in the field of persistent wound drainage after TJA and offers a classification of persistent wound drainage and an algorithmic approach to the decision-making process., Results: Available literature addressing the diagnosis and treatment of persistent wound drainage after TJA is scarce and an evidence-based clinical guideline is lacking. This is partially caused by the absence of a universally accepted definition of persistent wound drainage. In patients with persistent wound drainage, clinical signs and serological tests can be helpful in the diagnosis of a developing infection. Regarding the treatment of persistent wound drainage, nonsurgical treatment consists of absorbent dressings, pressure bandages, and temporary joint immobilization. Surgical treatment is advised when wound drainage persists for more than 5-7 days and consists of open debridement with irrigation and exchange of modular components and antimicrobial treatment., Conclusion: Based on this literature review, we proposed a classification and algorithmic approach for the management of patients with persistent wound drainage after TJA. Hopefully, this offers the orthopedic surgeon a practical clinical guideline by finding the right balance between overtreatment and undertreatment, weighing the risks and benefits. However, this classification and algorithmic approach should first be evaluated in a prospective trial., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Early acute periprosthetic joint infections (PJIs) treated with debridement, antibiotics and implant retention (DAIR) have failure rates ranging from 10% to 60%. We determined the efficacy of applying local gentamicin-impregnated beads and/or sponges during debridement in early PJI., Methods: Patients with early acute PJI, defined as less than 21 days of symptoms and treated with DAIR within 90 days after index surgery, were retrospectively evaluated. Early failure was defined as PJI-related death, the need for implant removal or a second DAIR or antibiotic suppressive therapy owing to persistent signs of infection, all within 60 days after initial debridement. Overall failure was defined as implant removal at any timepoint during follow-up. A 1:1 propensity score matching was performed to correct for confounding factors., Results: A total of 386 patients were included. Local gentamicin was applied in 293 patients (75.9%) and was withheld in 93 patients (24.1%). Multivariate analysis demonstrated that the use of local gentamicin was independently associated with early failure (OR = 1.97, 95% CI = 1.12-3.48). After propensity matching, early failure was 40.3% in the gentamicin group versus 26.0% in the control group (P = 0.06) and overall failure was 5.2% in the gentamicin group versus 2.6% in the control group (P = 0.40). These numbers remained when solely analysing the application of gentamicin-impregnated sponges., Conclusions: Even after propensity score matching, failure rates remained higher if local gentamicin-impregnated beads and/or sponges were administered in early acute PJI. Based on these results, their use should be discouraged.

Background: Debridement, antibiotics, and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C), and C-reactive protein >115 mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort., Methods: We retrospectively evaluated patients with early acute PJI treated with DAIR between 2006 and 2016 in 3 Dutch hospitals. Early acute PJI was defined as <21 days of symptoms and DAIR performed within 90 days after index surgery. Failure was defined as the need for (1) second DAIR, (2) implant removal, (3) suppressive antimicrobial treatment, or (4) infection-related death within 60 days after debridement., Results: A total of 386 patients were included. Failure occurred in 148 patients (38.3%). Patients with KLIC scores of ≤2, 2.5-3.5, 4-5, 5.5-6.5, and ≥7 had failure rates of 27.9%, 37.1%, 49.3%, 54.5%, and 85.7%, respectively (P < .001). The receiver-operating characteristic curve showed an area under the curve of 0.64 (95% confidence interval 0.59-0.69). A KLIC score higher than 6 points showed a specificity of 97.9%., Conclusion: The KLIC score is a relatively good preoperative risk score for DAIR failure in patients with early acute PJI and appears to be most useful in clinical practice for patients with low or high KLIC scores., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Diagnosing a chronic prosthetic joint infection (PJI) can be challenging. We hypothesized that obtaining preoperative tissue samples for culture in hip arthroplasty will increase the likelihood of diagnosing an infection before revision surgery. The aim of this cohort study was to determine the diagnostic accuracy of 2 tissue acquiring biopsy strategies to diagnose a PJI., Methods: Patients with a painful hip arthroplasty, in which a chronic PJI was suspected, were included. Tissue samples were obtained either by ultrasound guidance with a 16-Gauge needle (2012-2013) or in the operating room with a thick-bore needle (2013-2016). Revision surgery tissue biopsies were used as the gold standard. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio were calculated., Results: A total of 16 patients in the ultrasound cohort and 29 patients in the surgical cohort were included. Thirty-one percent (n = 14) were finally diagnosed with a PJI. The addition of thick bore needle tissue biopsies resulted in 9% more diagnosed PJIs compared with synovial fluid alone. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio was 33%, 85%, 33%, 85%, 2.2, and 0.8, respectively, for the ultrasound-guided biopsy cohort and 82%, 100%, 100%, 90%, infinite, and 0.2, respectively, for the surgical biopsy cohort., Conclusion: Obtaining multiple good quality tissue biopsies in a sterile environment will contribute to the diagnosis of a chronic PJI of the hip, with a higher diagnostic accuracy compared with ultrasound-guided thin needle biopsies and compared with synovial fluid culture alone., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To diagnose or exclude a chronic prosthetic joint infection (PJI) can be a clinical challenge. Therefore, sensitive and specific biomarkers are needed in the diagnostic work-up. Calprotectin is a protein with antimicrobial properties and is released by activated neutrophils, making it a specific marker for infection. Because of its low costs and ability to obtain a quantitative value as a point of care test, it is an attractive marker to use in clinical practice. In addition, the test is already used in routine care in most hospitals for other indications and therefore easy to implement., Methods: Between June 2015 and June 2017 we collected synovial fluid of all consecutive patients who underwent revision surgery of a prosthetic joint because of chronic pain with or without prosthetic loosening. Synovial calprotectin was measured using a lateral flow immunoassay. A PJI was defined by the diagnostic criteria described by the Musculoskeletal Infection Society., Results: Fifty-two patients with chronic pain were included. A PJI was diagnosed in 15 of 52 (29%) patients. The median calprotectin in the PJI group was 859 mg/L (interquartile range 86-1707) vs 7 mg/L (interquartile range 3-25) in the control group (P < .001). With a cut-off value of 50 mg/L, synovial calprotectin showed a sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 91.7%, 81.3%, and 94.4%, respectively., Conclusion: Synovial calprotectin is a useful and cheap biomarker to use in the diagnostic work-up of patients with chronic pain, especially to exclude a PJI prior to revision surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin., Methods: Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up., Results: Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains., Conclusion: Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Introduction: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are highly successful treatment modalities for advanced osteoarthritis. However, prolonged wound leakage after arthroplasty is linked to prosthetic joint infection (PJI), which is a potentially devastating complication. On the one hand, wound leakage is reported as a risk factor for PJI with a leaking wound acting as a porte d'entrée for micro-organisms. On the other hand, prolonged wound leakage can be a symptom of PJI. Literature addressing prolonged wound leakage is scarce, contradictory and of poor methodological quality. Hence, treatment of prolonged wound leakage varies considerably with both non-surgical and surgical treatment modalities. There is a definite need for evidence concerning the best way to treat prolonged wound leakage after joint arthroplasty., Methods and Analysis: A prospective nationwide randomised controlled trial will be conducted in 35 hospitals in the Netherlands. The goal is to include 388 patients with persistent wound leakage 9-10 days after THA or TKA. These patients will be randomly allocated to non-surgical treatment (pressure bandages, (bed) rest and wound care) or surgical treatment (debridement, antibiotics and implant retention (DAIR)). DAIR will also be performed on all non-surgically treated patients with persistent wound leakage at day 16-17 after index surgery, regardless of amount of wound leakage, other clinical parameters or C reactive protein. Clinical data are entered into a web-based database. Patients are asked to fill in questionnaires about disease-specific outcomes, quality of life and cost effectiveness at 3, 6 and 12 months after surgery. Primary outcome is the number of revision surgeries due to infection within a year of arthroplasty., Ethics and Dissemination: The Review Board of each participating hospital has approved the local feasibility. The results will be published in peer-reviewed scientific journals., Trial Registration Number: NTR5960;Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI., Patients and Methods: In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay., Results: The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI., Conclusion: Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. Cite this article: Bone Joint J 2017;99-B:660-5., (©2017 The British Editorial Society of Bone & Joint Surgery.)

Biomaterials-associated infection incidence represents an increasing clinical challenge as more people gain access to medical device technologies worldwide and microbial resistance to current approaches mounts. Few reported antimicrobial approaches to implanted biomaterials ever get commercialized for physician use and patient benefit. This is not for lack of ideas since many thousands of claims to new approaches to antimicrobial efficacy are reported. Lack of translation of reported ideas into medical products approved for use, results from conflicting goals and purposes between the various participants involved in conception, validation, development, commercialization, safety and regulatory oversight, insurance reimbursement, and legal aspects of medical device innovation. The scientific causes, problems and impressive costs of the limiting clinical options for combating biomaterials-associated infection are well recognized. Demands for improved antimicrobial technologies constantly appear. Yet, the actual human, ethical and social costs and consequences of their occurrence are less articulated. Here, we describe several clinical cases of biomaterials-associated infections to illustrate the often-missing human elements of these infections. We identify the current societal forces at play in translating antimicrobial research concepts into clinical implant use and their often-orthogonal constituencies, missions and policies. We assert that in the current complex environment between researchers, funding agencies, physicians, patients, providers, producers, payers, regulatory agencies and litigators, opportunities for translatable successes are minimized under the various risks assumed in the translation process. This argues for an alternative approach to more effectively introduce new biomaterials and device technologies that can address the clinical issues by providing patients and medical practitioners new options for desperate clinical conditions ineffectively addressed by biomedical innovation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We present a rare case of an immunocompetent host who developed a Candida albicans-infected total hip prosthesis. The infection could not be eradicated with debridement and extensive antifungal therapy. Our patient first underwent a resection of the proximal femur and local treatment with gentamicin-loaded cement beads. In a second procedure, a handmade cement spacer impregnated with voriconazole, amphotericin B, and vancomycin was placed. After 3 months of additional systemic antibiotic therapy, the patient remained afebrile, and a tumor prosthesis was placed. Six years postoperatively, she is doing well, walking with a small limp and no signs of recurrent infection. This is the first report on elution of voriconazole and amphotericin B from bone cement delivered at clinically significant concentrations for at least 72 hours., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Biomaterial-associated infections occur on both permanent implants and temporary devices for restoration or support of human functions. Despite increasing use of biomaterials in an aging society, comparatively few biomaterials have been designed that effectively reduce the incidence of biomaterial-associated infections. This review provides design guidelines for infection-reducing strategies based on the concept that the fate of biomaterial implants or devices is a competition between host tissue cell integration and bacterial colonization at their surfaces.