Bacteria Living in Biofilms in Fluids: Could Chemical Antibiofilm Pretreatment of Culture Represent a Paradigm Shift in Diagnostics?

Biofilms are multicellular aggregates of bacteria immersed in an extracellular matrix that forms on various surfaces, including biological tissues and artificial surfaces. However, more and more reports point out the fact that even biological fluids and semifluid, such as synovial liquid, blood, urine, or mucus and feces, harbor "non-attached" biofilm aggregates of bacteria, which represent a significant phenomenon with critical clinical implications that remain to be fully investigated. In particular, biofilm aggregates in biological fluid samples have been shown to play a relevant role in bacterial count and in the overall accuracy of microbiological diagnosis. In line with these observations, the introduction in the clinical setting of fluid sample pretreatment with an antibiofilm chemical compound called dithiothreitol (DTT), which is able to dislodge microorganisms from their intercellular matrix without killing them, would effectively improve the microbiological yield and increase the sensitivity of cultural examination, compared to the current microbiological techniques. While other ongoing research continues to unveil the complexity of biofilm formation in biological fluids and its impact on infection pathogenesis and diagnosis, we here hypothesize that the routine use of a chemical antibiofilm pretreatment of fluid and semi-solid samples may lead to a paradigm shift in the microbiological approach to the diagnosis of biofilm-related infections and should be further investigated and eventually implemented in the clinical setting.

Is nanomaterial- and vancomycin-loaded polymer coating effective at preventing methicillin-resistant Staphylococcus aureus growth on titanium disks? An in vitro study.

PURPOSE: Periprosthetic joint infections induced by methicillin-resistant Staphylococcus aureus (MRSA) pose a major socioeconomic burden. Given the fact that MRSA carriers are at high risk for developing periprosthetic infections regardless of the administration of eradication treatment pre-operatively, the need for developing new prevention modalities is high. METHODS: The antibacterial and antibiofilm properties of vancomycin, Al2O3 nanowires, and TiO2 nanoparticles were evaluated in vitro using MIC and MBIC assays. MRSA biofilms were grown on titanium disks simulating orthopedic implants, and the infection prevention potential of vancomycin-, Al2O3 nanowire-, and TiO2 nanoparticle-supplemented Resomer® coating was evaluated against biofilm controls using the XTT reduction proliferation assay. RESULTS: Among the tested modalities, high- and low-dose vancomycin-loaded Resomer® coating yielded the most satisfactory metalwork protection against MRSA (median absorbance was 0.1705; [IQR = 0.1745] vs control absorbance 0.42 [IQR = 0.07]; p = 0.016; biofilm reduction was 100%; and 0.209 [IQR = 0.1295] vs control 0.42 [IQR = 0.07]; p < 0.001; biofilm reduction was 84%, respectively). On the other hand, polymer coating alone did not provide clinically meaningful biofilm growth prevention (median absorbance was 0.2585 [IQR = 0.1235] vs control 0.395 [IQR = 0.218]; p < 0.001; biofilm reduction was 62%). CONCLUSIONS: We advocate that apart from the well-established preventative measures for MRSA carriers, loading implants with bioresorbable Resomer® vancomycin-supplemented coating may decrease the incidence of early post-op surgical site infections with titanium implants. Of note, the payoff between localized toxicity and antibiofilm efficacy should be considered when loading polymers with highly concentrated antimicrobial agents.

Dithiotreitol pre-treatment of synovial fluid samples improves microbiological counts in peri-prosthetic joint infection.

PURPOSE: Synovial fluid cultures of periprosthetic joint infections (PJI) may be limited by bacteria living in the fluids as biofilm-aggregates. The antibiofilm pre-treatment of synovial fluids with dithiotreitol (DTT) could improve bacterial counts and microbiological early stage diagnosis in patients with suspected PJI. METHODS: Synovial fluids collected from 57 subjects, affected by painful total hip or knee replacement, were divided into two aliquots, one pre-treated with DTT and one with normal saline. All samples were plated for microbial counts. Sensitivity of cultural examination and bacterial counts of pre-treated and control samples were then calculated and statistically compared. RESULTS: Dithiothreitol pre-treatment led to a higher number of positive samples, compared to controls (27 vs 19), leading to a statistically significant increase in the sensitivity of the microbiological count examination from 54.3 to 77.1% and in colony-forming units count from 1884 ± 2.129 CFU/mL with saline pre-treatment to 20.442 ± 19.270 with DTT pre-treatment (P = 0.02). CONCLUSIONS: To our knowledge, this is the first report showing the ability of a chemical antibiofilm pre-treatment to increase the sensitivity of microbiological examination in the synovial fluid of patients with peri-prosthetic joint infection. If confirmed by larger studies, this finding may have a significant impact on routine microbiological procedures applied to synovial fluids and brings further support to the key role of bacteria living in biofilm-formed aggregates in joint infections.

Infections of Tumor Prostheses: An Updated Review on Risk Factors, Microbiology, Diagnosis, and Treatment Strategies.

Several causes contribute to the high infection rate in tumor prostheses, including extensive tissue dissection and patients' immunosuppression due to the neoplastic disease. Most of these infections develop within the first 2 years following surgery with 70% of them occurring during the first year, while they are often associated with a low pathogen burden. The pathogenesis of infections in tumor prostheses is linked to bacteria developing in biofilms. Approximately half of them are caused by Staphylococcus spp., followed by Streptococcus spp., Enterococcus spp., and Enterobacteriaceae spp., while multiple pathogens may be isolated in up to 25% of the cases, with coagulase-negative Staphylococci (CoNS) and Enterococccus spp. being the most frequent pair. Although early detection and timely management are essential for complete resolution of these challenging infections, prompt diagnosis is problematic due to the highly varying clinical symptoms and the lack of specific preoperative and intraoperative diagnostic tests. Surgical management with one- or two-stage revision surgery is the mainstay for successful eradication of these infections. The recent advances in laboratory diagnostics and the development of biofilm-resistant prostheses over the past years have been areas of great interest, as research is now focused on prevention strategies. The aim of this study is to review and consolidate the current knowledge regarding the epidemiology, risk factors, microbiology, and diagnosis of infections of tumor prostheses, and to review the current concepts for their treatment and outcomes.

Viral infections in orthopedics: A systematic review and classification proposal.

BACKGROUND: Although the impact of microbial infections on orthopedic clinical outcomes is well recognized, the influence of viral infections on the musculoskeletal system might have been underestimated. AIM: To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the Reference Citation Analysis (RCA), and Scopus for completed studies published before January 30, 2021, to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies, Moga score for case series, Wylde score for registry studies, and Newcastle-Ottawa Scale for case-control studies. RESULTS: Six human and four animal studies were eligible for inclusion in the qualitative synthesis. Hepatitis C virus was implicated in several peri- and post-operative complications in patients without cirrhosis after major orthopedic surgery. Herpes virus may affect the integrity of lumbar discs, whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss. CONCLUSION: Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis. Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms. Therefore, based on our literature search, the proposed clinical and pathogenetic classification scheme is as follows: (1) Viral infections of bone or joint; (2) Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues; and (3) Viral infection as a risk factor for post-surgical bacterial infection.

Megaprostheses for the revision of infected hip arthroplasties with severe bone loss.

BACKGROUND: Periprosthetic hip infections with severe proximal femoral bone loss may require the use of limb salvage techniques, but no agreement exists in literature regarding the most effective treatment. Aim of this study is to analyze the infection eradication rate and implant survival at medium-term follow-up in patients treated with megaprostheses for periprosthetic hip infections with severe bone loss. METHODS: Twenty-one consecutive patients were retrospectively reviewed at a mean 64-month follow-up (24-120). Functional and pain scores, microbiological, radiological and intraoperative findings were registered. Kaplan Meier survival analysis and log rank test were used for infection free survival and implant survival analyses. RESULTS: The infection eradication rate was 90.5%, with an infection free survival of 95.2% at 2 years (95%CI 70.7-99.3) and 89.6%(95%CI 64.3-97.3) at 5 years. Only two patients required major implant revisions for aseptic implant loosening. The most frequent complication was dislocation (38.1%). The major revision-free survival of implants was 95.2% (95%CI 70.7-99.3) at 2 years and 89.6% (95%CI 64.3-97.3) at 5 years. The overall implant survival was 83.35% (CI95% 50.7-93.94) at 2 and 5 years. Subgroup analyses (cemented versus cementless MPs, coated versus uncoated MPs) revealed no significant differences at log rank test, but its reliability was limited by the small number of patients included. CONCLUSIONS: Proximal femoral arthroplasty is useful to treat periprosthetic hip infections with severe bone loss, providing good functional results with high infection eradication rates and rare major revisions at medium-term follow-up. No conclusions can be drawn on the role of cement and coatings.

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.].

The Role of Imaging Techniques to Define a Peri-Prosthetic Hip and Knee Joint Infection: Multidisciplinary Consensus Statements.

Diagnosing a peri-prosthetic joint infection (PJI) remains challenging despite the availability of a variety of clinical signs, serum and synovial markers, imaging techniques, microbiological and histological findings. Moreover, the one and only true definition of PJI does not exist, which is reflected by the existence of at least six different definitions by independent societies. These definitions are composed of major and minor criteria for defining a PJI, but most of them do not include imaging techniques. This paper highlights the pros and cons of available imaging techniques-X-ray, ultrasound, computed tomography (CT), Magnetic Resonance Imaging (MRI), bone scintigraphy, white blood cell scintigraphy (WBC), anti-granulocyte scintigraphy, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), discusses the added value of hybrid camera systems-single photon emission tomography/computed tomography (SPECT/CT), PET/CT and PET/MRI and reports consensus answers on important clinical questions that were discussed during the Third European Congress on Inflammation/Infection Imaging in Rome, December 2019.

The W.A.I.O.T. Definition of Peri-Prosthetic Joint Infection: A Multi-center, Retrospective Validation Study.

Peri-prosthetic joint infection (PJI) definition plays an important role in diagnostic and therapeutic decisions. However, while several criteria have been proposed by eminent institutions to define a PJI in the last decade, their clinical validation has been rarely performed. Aim of the present multicenter, international, retrospective study was to validate the World Association against Infection in Orthopedics and Trauma (WAIOT) pre/intra-operative PJI definition with post-operative confirmatory tests. A total of 210 patients, undergoing hip (n = 86) or knee (n = 124) revision surgery for any reason in six orthopedic centers in Africa, Asia, Europe and South America, were retrospectively evaluated at a two years minimum follow-up after surgery. All the available pre-, intra- and post-operative findings were collected and analyzed according to the WAIOT criteria, which include a set of tests to confirm (Rule In) or to exclude (Rule Out) a PJI. On average, patients were investigated pre/intra-operatively with 3.1 ± 1.1 rule out and 2.7 ± 0.9 rule in tests; the presence of a fistula or exposed implant was reported in 37 patients (17.6%). According to pre/intraoperative findings, 36.2% of the patients were defined as affected by high-grade PJI (n = 76; average score: 2.3 ± 0.8), 21.9% by low-grade PJI (n = 46; average score: 0.8 ± 0.8), 10.5% by biofilm-related implant malfunction (n = 22; average score: -1.6 ± 0.8), 2.9% as contamination (n = 6; average score: -3.5 ± 1.0), and 28.6% as no infection (n = 60; average score: -3.0 ± 1.4). Pre/intra-operative PJI definitions matched post-operative confirmatory tests, in 97.1% of the patients. This is, to our knowledge, one of the largest study ever conducted to validate a PJI definition The retrospective analysis in different centers was greatly facilitated by the structure of the WAIOT definition, that allows to include different tests on the basis of their sensitivity/specificity, while the comparison between pre/intra-operative and post-operative findings offered the internal validation of the scoring system. Our results authenticate the WAIOT definition as a reliable, simple tool to identify patients affected by PJI prior to joint revision surgery.

Loud and silent epidemics in the third millennium: tuning-up the volume.

The media play a key role in promoting public health and influencing debate regarding health issues; however, some topics seem to generate a stronger response in the public, and this may be related to how the media construct and deliver their messages. Mass media coverage of COVID-19 epidemic has been exceptional with more than 180,000 articles published each day in 70 languages from March 8 to April 8, 2020. One may well wonder if this massive media attention ever happened in the past and if it has been finally proven to be beneficial or even just appropriate. Surgical site and implant-related infections represent a substantial part of health care-associated infections; with an estimated overall incidence of 6% post-surgical infection, approximately 18 million new surgical site infections are expected each year globally, with 5 to 10% mortality rate and an astounding economic and social cost. In the current mediatic era, orthopaedic surgeons need to refocus some of their time and energies from surgery to communication and constructive research. Only raising mediatic awareness on surgical site and implant-related infections may tune up the volume of silent epidemics to a level that can become audible by governing institutions.

The World Association against Infection in Orthopaedics and Trauma (WAIOT) procedures for Microbiological Sampling and Processing for Periprosthetic Joint Infections (PJIs) and other Implant-Related Infections.

While implant-related infections continue to play a relevant role in failure of implantable biomaterials in orthopaedic and trauma there is a lack of standardised microbiological procedures to identify the pathogen(s). The microbiological diagnosis of implant-related infections is challenging due to the following factors: the presence of bacterial biofilm(s), often associated with slow-growing microorganisms, low bacterial loads, previous antibiotic treatments and, possible intra-operative contamination. Therefore, diagnosis requires a specific set of procedures. Based on the Guidelines of the Italian Association of the Clinical Microbiologists (AMCLI), the World Association against Infection in Orthopaedics and Trauma has drafted the present document. This document includes guidance on the basic principles for sampling and processing for implant-related infections based on the most relevant literature. These procedures outline the main microbiological approaches, including sampling and processing methodologies for diagnostic assessment and confirmation of implant-related infections. Biofilm dislodgement techniques, incubation time and the role of molecular approaches are addressed in specific sections. The aim of this paper is to ensure a standardised approach to the main microbiological methods for implant-related infections, as well as to promote multidisciplinary collaboration between clinicians and microbiologists.

The W.A.I.O.T. Definition of High-Grade and Low-Grade Peri-Prosthetic Joint Infection.

The definition of peri-prosthetic joint infection (PJI) has a strong impact on the diagnostic pathway and on treatment decisions. In the last decade, at least five different definitions of peri-prosthetic joint infection (PJI) have been proposed, each one with intrinsic limitations. In order to move a step forward, the World Association against Infection in Orthopedics and Trauma (W.A.I.O.T.) has studied a possible alternative solution, based on three parameters: 1. the relative ability of each diagnostic test or procedure to Rule OUT and/or to Rule IN a PJI; 2. the clinical presentation; 3. the distinction between pre/intra-operative findings and post-operative confirmation. According to the WAIOT definition, any positive Rule IN test (a test with a specificity > 90%) scores +1, while a negative Rule OUT test (a test with a sensitivity > 90%) scores -1. When a minimum of two Rule IN and two Rule OUT tests are performed in a given patient, the balance between positive and negative tests, interpreted in the light of the clinical presentation and of the post-operative findings, allows to identify five different conditions: High-Grade PJI (score ≥ 1), Low-Grade PJI (≥0), Biofilm-related implant malfunction, Contamination and No infection (all scoring < 0). The proposed definition leaves the physician free to choose among different tests with similar sensitivity or specificity, on the basis of medical, logistical and economic considerations, while novel tests or diagnostic procedures can be implemented in the definition at any time, provided that they meet the required sensitivity and/or specificity thresholds. Key procedures to confirm or to exclude the diagnosis of PJI remain post-operative histological and microbiological analysis; in this regard, given the biofilm-related nature of PJI, microbiological investigations should be conducted with proper sampling, closed transport systems, antibiofilm processing of tissue samples and explanted biomaterials, and prolonged cultures. The proposed WAIOT definition is the result of an international, multidisciplinary effort. Next step will be a large scale, multicenter clinical validation trial.

Alpha defensin, leukocyte esterase, C-reactive protein, and leukocyte count in synovial fluid for pre-operative diagnosis of periprosthetic infection.

Synovial fluid analysis for diagnosis of prosthetic joint infections has gained increasing interest in the recent past when markers more specific for these infections than the serum ones have been identified. Despite the important steps forward, identification of a gold standard has not yet been identified. In this study, usefulness of alpha defensin, leukocyte esterase, C-reactive protein (CRP), and white blood cells (WBCs) in synovial fluids alone and in combination for diagnosis of prosthetic joint infection was evaluated. Synovial fluids from 32 infected and 34 not infected patients were analyzed. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and receiver-operating characteristic (ROC) curves were calculated for each parameter. Moreover, combination of coupled variables was also evaluated by logistic regression analysis. Sensitivity of alpha defensin, CRP, leukocyte count, and leukocyte esterase were 84.4%, 87.5%, 93.7%, and 93.8%, respectively. Specificity was 91.2% for leukocyte counts, 94.1% for alpha defensin, 97.0% for CRP, and 97.1% for leukocyte esterase. Diagnostic accuracy was 89.4% for alpha defensin, 92.4% for WBC counts and CRP, and 95.5% for leukocyte esterase. No statistical differences were observed in area under the curve (AUC) of the ROC curves of alpha defensin, CRP, and leukocyte counts. Logistic regression analysis applied to a model comprising all the variables showed an AUC higher than AUC of coupled variables. In conclusion, results of this study confirm the high sensitivity and specificity of synovial leukocyte esterase for diagnosis of prosthetic joint infection, also suggesting the need to assess a panel of markers to optimize diagnosis of these infections.

One-stage exchange with antibacterial hydrogel coated implants provides similar results to two-stage revision, without the coating, for the treatment of peri-prosthetic infection.

PURPOSE: Aim of this study was to verify the hypothesis that a one-stage exchange procedure, performed with an antibiotic-loaded, fast-resorbable hydrogel coating, provides similar infection recurrence rate than a two-stage procedure without the coating, in patients affected by peri-prosthetic joint infection (PJI). METHODS: In this two-center case-control, study, 22 patients, treated with a one-stage procedure, using implants coated with an antibiotic-loaded hydrogel [defensive antibacterial coating (DAC)], were compared with 22 retrospective matched controls, treated with a two-stage revision procedure, without the coating. RESULTS: At a mean follow-up of 29.3 ± 5.0 months, two patients (9.1%) in the DAC group showed an infection recurrence, compared to three patients (13.6%) in the two-stage group. Clinical scores were similar between groups, while average hospital stay and antibiotic treatment duration were significantly reduced after one-stage, compared to two-stage (18.9 ± 2.9 versus 35.8 ± 3.4 and 23.5 ± 3.3 versus 53.7 ± 5.6 days, respectively). CONCLUSIONS: Although in a relatively limited series of patients, our data shows similar infection recurrence rate after one-stage exchange with DAC-coated implants, compared to two-stage revision without coating, with reduced overall hospitalization time and antibiotic treatment duration. These findings warrant further studies in the possible applications of antibacterial coating technologies to treat implant-related infections. LEVEL OF EVIDENCE: III.

Presepsin: A potential biomarker of PJI? A comparative analysis with known and new infection biomarkers.

There is still no "gold standard" for the diagnosis and prognosis of post-operative periprosthetic joint infection (PJI). Among serum biomarkers, an emerging molecule is presepsin, the soluble fraction of CD14, recently described in other settings as a powerful diagnostic tool to detect sepsis at different degrees of severity. The aim of this study was to investigate the diagnostic and prognostic value of presepsin in PJI. A total of 30 patients with PJI and 30 patients without PJI were enrolled. Presepsin, C-reactive protein (CRP), serum interleukin (IL)-6, triggering receptor expressed on myeloid cells 1 (TREM-1), CCL2, matrix metalloproteinase 9 (MMP-9), CD163, osteopontin (OPN), and toll-like receptor 2 (TLR2) were measured at different times after surgery. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Presepsin showed greater diagnostic value than CRP and IL-6; CD163, TREM-1, and MMP-9 had very low diagnostic potential. Presepsin, OPN, CCL2, suPAR, and TLR2 all decreased significantly with increasing time of recovery after surgery in PJI patients. Presepsin can be considered a useful tool for the diagnosis and clinical monitoring of PJI and can be backed by a panel of new inflammatory markers involved in monocyte-/macrophage-mediated inflammatory responses, such as OPN, CCL2, TLR2, and suPAR.

Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: a multicenter randomized controlled trial.

BACKGROUND: Infection is one of the main reasons for failure of orthopedic implants. Antibacterial coatings may prevent bacterial adhesion and biofilm formation, according to various preclinical studies. The aim of the present study is to report the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating (Defensive Antibacterial Coating, DAC®) to prevent surgical site infection, in patients undergoing internal osteosynthesis for closed fractures. MATERIALS AND METHODS: In this multicenter randomized controlled prospective study, a total of 256 patients in five European orthopedic centers who were scheduled to receive osteosynthesis for a closed fracture, were randomly assigned to receive antibiotic-loaded DAC or to a control group (without coating). Pre- and postoperative assessment of laboratory tests, wound healing, clinical scores and X-rays were performed at fixed time intervals. RESULTS: Overall, 253 patients were available with a mean follow-up of 18.1 ± 4.5 months (range 12-30). On average, wound healing, clinical scores, laboratory tests and radiographic findings did not show any significant difference between the two groups. Six surgical site infections (4.6%) were observed in the control group compared to none in the treated group (P < 0.03). No local or systemic side-effects related to the DAC hydrogel product were observed and no detectable interference with bone healing was noted. CONCLUSIONS: The use of a fast-resorbable antibiotic-loaded hydrogel implant coating provides a reduced rate of post-surgical site infections after internal osteosynthesis for closed fractures, without any detectable adverse event or side-effects. LEVEL OF EVIDENCE: 2.

The Concept of Biofilm-Related Implant Malfunction and "Low-Grade Infection".

Biofilms have a tremendous impact on industrial machines working in moist environments, while in biological systems their effect is further complicated by the host's response.Implant-related infections are a complex process, starting with bacterial adhesion and biofilm formation, followed by the variable interaction between host, implant, microorganisms and their by-products. Depending on the balance of these factors, different clinical presentations are observed, which may eventually, at times, shift from one into the other.-"Implant malfunction" displays only mild clinical signs/symptoms - light pain and/or slight soft tissue contracture or functional impairment - with negative infection/inflammatory markers; it requires prolonged cultures, antibiofilm and eventually genomic investigations for pathogen detection;-"Low-grade infection" features recurrent or persistent pain and/or soft tissue contracture with various functional impairment and mixed positive/negative markers of infection/inflammation; pathogen identification requires prolonged cultures and antibiofilm techniques;-"High-grade infection" displays classical signs/symptoms of infection/inflammation with positive tests; pathogen identification is often possible with traditional microbiological techniques, but is better achieved with prolonged cultures and antibiofilm processing.Understanding biofilms-related clinical presentations is crucial for physicians, to implement the best diagnostic and therapeutic measures, and for regulatory bodies, to define the evaluation process of technologies aimed at reducing implants' malfunctions and infections, like anti-adhesive and antibiofilm coatings, that should be regulated as (part of) medical devices, requiring a suitable post-marketing surveillance.Only an effective antibiofilm-targeted approach from all players will hopefully allow the medical community to mitigate the current unacceptable social and economical burden of implant-related infections and malfunctions.

Algorithm to Diagnose Delayed and Late PJI: Role of Joint Aspiration.

Total Joint Arthroplasty (TJA) continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. A devastating complication after TJA is infection. Periprosthetic joint infection (PJI), represents one of the major causes of failure and remains a significant challenge facing orthopaedics today. PJI usually requires additional surgery including revision of the implants, fusion or amputations causing tremendous patient suffering but also a heavy health economics burden. PJI is at the origin of around 20-25 % of total knee arthroplasty (Bozic et al. 2010; de Gorter et al. 2015; Sundberg et al. 2015) and 12-15 % of total hip arthroplasty (Bozic et al. 2009; Garellick et al. 2014; de Gorter et al. 2015) failures.