Fellowship Training in Arthroplasty Improves Treatment Success of Debridement, Antibiotics, and Implant Retention for Periprosthetic Knee Infections.

Background: Debridement, antibiotics, and implant retention (DAIR) is a well-accepted surgical strategy for periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). DAIR in TKA may be incorrectly thought of as a "simple" procedure not requiring formal specialized training in arthroplasty. Currently, there are no studies comparing the risk of treatment failure based on surgeon fellowship training. Methods: A retrospective review was performed of consecutive patients who underwent DAIR for TKA PJI at our institution. Two cohorts were created based on whether DAIR was performed by an arthroplasty fellowship-trained (FT) surgeon or nonarthroplasty fellowship-trained (NoFT) surgeon. Primary outcome was treatment failure following DAIR at a minimum of 1 year postoperatively. Treatment failure was based on the Tier 1 International Consensus Meeting definition of infection control. Secondary outcomes were also recorded including death during the totality of PJI treatment. Results: A total of 112 patients were identified (FT = 68, NoFT = 44). At a mean follow-up of 7.3 years [standard deviation = 3.9], 73 patients (59.8%) failed treatment. Fellowship training in arthroplasty significantly improved treatment success rates (FT, 35/68 [51.5%]; NoFT, 10/44 [22.7%]; odds ratio 2.5 [95% confidence interval 1.1 to 5.9; P = .002]). Survivorship also differed significantly between the cohorts; at timepoints of 1.5 months, 5 months, 30 months, and 180 months, survivorship of the FT cohort was 79.4%, 67.6%, 54.4%, and 50.7%, respectively, compared with a survivorship of 65.9%, 52.3%, 25%, and 22.7% in the NoFT cohort (P = .002). Conclusions: TKA PJI treated with DAIR should not be considered a simple procedure. Improved treatment success may be associated with subspecialty fellowship training in arthroplasty. Level of Evidence: IV.

Lower Rates of Reoperation Following Partial or Complete Revision Arthroplasty Compared to Debridement, Antibiotics, and Implant Retention for Early Postoperative and Acute Hematogenous Periprosthetic Hip Infection.

BACKGROUND: This study aimed to: 1) compare treatment outcomes between debridement, antibiotics, and implant retention (DAIR) and partial or complete revision arthroplasty (RA) for early postoperative and acute hematogenous total hip arthroplasty periprosthetic joint infection (PJI) and 2) identify factors associated with treatment outcome. METHODS: The study consisted of a retrospective cohort of patients who underwent surgery for PJI between 2004 and 2021. There were 76 patients (74.5%) who underwent DAIR and 26 patients (25.5%) who underwent RA. Treatment success was defined as treatment eradication at a minimum of a 2-year follow up. Bivariate regression analysis was used to assess the effect of different factors on treatment outcomes. Kaplan-Meier survivorship was performed to compare survivorship between cohorts. RESULTS: At a mean follow-up of 8.2 years (range, 2.2 to 16.4), significantly more DAIR failed treatment (DAIR, 50 [65.8%]; 10 [38.5%]; P = .015). The 8-year Kaplan-Meier survivorship was 35.1% [95% confidence interval (CI), 24.3 to 45.9] for patients treated with DAIR and 61.5% [95% CI, 42.9 to 80.1] for those treated with RA (log rank = 0.039). Bivariate regression analysis showed performing a RA was associated with a higher likelihood of treatment success (odds ratio 4.499, 95% CI 1.600 to 12.647, P = .004), whereas a higher body mass index was associated with treatment failure (odds ratio 0.934, 95% CI 0.878 to 0.994, P = .032). CONCLUSIONS: To reduce the rate of recalcitrant infection following early postoperative or acute hematogenous total hip arthroplasty PJI, RA may be of benefit over DAIR. This is especially relevant in the early postoperative period, when components can be readily exchanged.

Combining bacteriophage and vancomycin is efficacious against MRSA biofilm-like aggregates formed in synovial fluid.

Background: Biofilm formation is a major clinical challenge contributing to treatment failure of periprosthetic joint infection (PJI). Lytic bacteriophages (phages) can target biofilm associated bacteria at localized sites of infection. The aim of this study is to investigate whether combination therapy of phage and vancomycin is capable of clearing Staphylococcus aureus biofilm-like aggregates formed in human synovial fluid. Methods: In this study, S. aureus BP043, a PJI clinical isolate was utilized. This strain is a methicillin-resistant S. aureus (MRSA) biofilm-former. Phage Remus, known to infect S. aureus, was selected for the treatment protocol. BP043 was grown as aggregates in human synovial fluid. The characterization of S. aureus aggregates was assessed for structure and size using scanning electron microscopy (SEM) and flow cytometry, respectively. Moreover, the formed aggregates were subsequently treated in vitro with: (a) phage Remus [∼108 plaque-forming units (PFU)/ml], (b) vancomycin (500 µg/ml), or (c) phage Remus (∼108 PFU/ml) followed by vancomycin (500 µg/ml), for 48 h. Bacterial survival was quantified by enumeration [colony-forming units (CFU)/ml]. The efficacy of phage and vancomycin against BP043 aggregates was assessed in vivo as individual treatments and in combination. The in vivo model utilized Galleria mellonella larvae which were infected with BP043 aggregates pre-formed in synovial fluid. Results: Scanning electron microscopy (SEM) images and flow cytometry data demonstrated the ability of human synovial fluid to promote formation of S. aureus aggregates. Treatment with Remus resulted in significant reduction in viable S. aureus residing within the synovial fluid aggregates compared to the aggregates that did not receive Remus (p < 0.0001). Remus was more efficient in eliminating viable bacteria within the aggregates compared to vancomycin (p < 0.0001). Combination treatment of Remus followed by vancomycin was more efficacious in reducing bacterial load compared to using either Remus or vancomycin alone (p = 0.0023, p < 0.0001, respectively). When tested in vivo, this combination treatment also resulted in the highest survival rate (37%) 96 h post-treatment, compared to untreated larvae (3%; p < 0.0001). Conclusion: We demonstrate that combining phage Remus and vancomycin led to synergistic interaction against MRSA biofilm-like aggregates in vitro and in vivo.

Combining povidone-iodine with vancomycin can be beneficial in reducing early biofilm formation of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus on titanium surface.

There is controversial clinical evidence regarding the added antibacterial benefit of locally administering antiseptic solutions or antibiotics to the infected joint space. The objectives of this in vitro study were to test the efficacy of povidone-iodine (PVP-I) and vancomycin in treating premature and developed Staphylococcus aureus biofilms grown on titanium implant surfaces. PVP-I and vancomycin were used to treat immature and developed biofilms formed by two clinical strains of S. aureus (BP043-MRSA, PB011-MSSA). S. aureus strains were grown as immature (3 h-old) or developed (24 h-old) biofilm. These biofilms were grown on titanium plasma sprayed discs. The treatment regimens tested were: 0.8% PVP-I, 500 µg/ml vancomycin as well as a combination of vancomycin and PVP-I. PVP-I was tested at 3 min, as per current clinical practice, versus 1 min treatment times. In addition, the cytotoxicity of the PVP-I and vancomycin was tested using fresh skeletal muscle tissue cores harvested from the rat's abdominal muscles using alamarBlue assay. The combination of PVP-I (3 min) and vancomycin (24 h.) showed synergistic interaction and the best efficacy against immature biofilms formed by both clinical strains. This degree of eradication was statistically significant compared to the untreated control, p < .0001. However, this combination therapy had limited efficiency against developed biofilms. Also, PVP-I alone was more effective when exposure time was 3 min instead of 1 min against immature biofilm for MRSA, p = .02, and MSSA, p = .01. PVP-I and vancomycin were not effective against developed biofilm regardless of exposure time. Also, combining PVP-I and vancomycin was not cytotoxic to muscle tissue. Combining PVP-I with vancomycin is superior in reducing viable S. aureus cells in immature biofilms grown on titanium surface without causing significant cytotoxicity to muscle tissue. Exposure times and biofilm maturity play a role in dictating the efficacy of using local antiseptics and antibiotics to treat biofilms on implant surfaces.

Establishment of a Novel Rat Model of Gram-Negative Periprosthetic Joint Infection Using Cementless Hip Hemiarthroplasty.

BACKGROUND: Gram-negative periprosthetic joint infections (GN-PJIs) present unique challenges. Our aim was to establish a clinically representative GN-PJI model that recapitulates biofilm formation in vivo. We also hypothesized that biofilm formation on the implant surface would affect its ability to osseointegrate. METHODS: Three-dimensionally-printed medical-grade titanium hip implants were used to replace the femoral heads of male Sprague-Dawley rats. GN-PJI was induced using 2 bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real time using an in vivo imaging system (IVIS) and magnetic resonance imaging (MRI). Bacterial loads were quantified utilizing the viable colony count. Biofilm formation at the bone-implant interface was visualized using field-emission scanning electron microscopy (FE-SEM). Implant stability, as an outcome, was directly assessed by quantifying osseointegration using microcomputed tomography, and indirectly assessed by identifying gait-pattern changes. RESULTS: Bioluminescence detected by the IVIS was focused on the hip region and demonstrated localized infection, with greater ability of PA14-lux to persist in the model compared with the ΔflgK-lux strain, which is defective in biofilm formation. This was corroborated by MRI, as PA14-lux induced relatively larger implant-related abscesses. Biofilm formation at the bone-implant interface induced by PA14-lux was visualized using FE-SEM versus defective-biofilm formation by ΔflgK-lux. Quantitatively, the average viable colony count of the sonicated implants, in colony-forming units/mL, was 3.77 × 108 for PA14-lux versus 3.65 × 103 for ΔflgK-lux, with a 95% confidence interval around the difference of 1.45 × 108 to 6.08 × 108 (p = 0.0025). This difference in the ability to persist in the model was reflected significantly on implant osseointegration, with a mean intersection surface of 4.1 × 106 ± 1.99 × 106 µm2 for PA14-lux versus 6.44 × 106 ± 2.53 × 106 µm2 for ΔflgK-lux and 7.08 × 106 ± 1.55 × 106 µm2 for the noninfected control (p = 0.048). CONCLUSIONS: To our knowledge, this proposed, novel in vivo biofilm-based model is the most clinically representative for GN-PJI to date, since animals can bear weight on the implant, poor osseointegration was associated with biofilm formation, and localized PJI was assessed by various modalities. CLINICAL RELEVANCE: This model will allow for more reliable testing of novel biofilm-targeting therapeutics.

Is the routine use of local antibiotics in the management of periprosthetic joint infections justified?

Periprosthetic joint infection (PJI) following total hip and total knee arthroplasty continues to be a leading cause of re-operation and revision arthroplasty. Not only is the treatment of PJI notoriously challenging, but success rates are variable. Regardless of the surgical strategy used, successful management of PJI requires a comprehensive surgical debridement focused at eradicating the underlying biofilm followed by appropriate antimicrobial therapy. Although systemic antimicrobial delivery continues to be a cornerstone in the treatment of PJI, many surgeons have started using local antibiotics to deliver higher concentrations of antibiotics directly into the vulnerable joint and adjacent soft tissues, which often have compromised vascularity. Available evidence on the use of topical powder, bone cement, and calcium sulphate carriers for local delivery of antibiotics during the initial treatment of PJI is limited to studies that are extremely heterogeneous. There is currently no level-1 evidence to support routinely using these products. Further, appropriately powered, prospective studies are needed to quantify the safety and efficacy of antibiotic-located calcium-sulphate carriers to justify their added costs. These products should not encourage surgeons to deviate from best practice guidelines, such as those recommended during the International Consensus Meeting on Musculoskeletal Infections.

Periprosthetic joint infection following hip hemiarthroplasty : factors associated with infection and treatment outcome.

AIMS: The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. METHODS: A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years' follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. RESULTS: A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). CONCLUSION: HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components.Cite this article: Bone Jt Open 2022;3(12):924-932.

Management of Periprosthetic Joint Infections After Hemiarthroplasty of the Hip: A Critical Analysis Review.

➢: Periprosthetic joint infection (PJI) following hip hemiarthroplasty (HA) is a devastating complication, incurring immense health-care costs associated with its treatment and placing considerable burden on patients and their families. These patients often require multiple surgical procedures, extended hospitalization, and prolonged antimicrobial therapy. ➢: Notable risk factors include older age, higher American Society of Anesthesiologists (ASA) score, inadequate antibiotic prophylaxis, non-antibiotic-loaded cementation of the femoral implant, longer duration of the surgical procedure, and postoperative drainage and hematoma. ➢: Although the most frequent infecting organisms are gram-positive cocci such as Staphylococcus aureus, there is a higher proportion of patients with gram-negative and polymicrobial infections after hip HA compared with patients who underwent total hip arthroplasty. ➢: Several surgical strategies exist. Regardless of the preferred surgical treatment, successful management of these infections requires a comprehensive surgical debridement focused on eradicating the biofilm followed by appropriate antibiotic therapy. ➢: A multidisciplinary approach led by surgeons familiar with PJI treatment and infectious disease specialists is recommended for all cases of PJI after hip HA to increase the likelihood of treatment success.

Free Functional Muscle Transfer following Upper Extremity Sarcoma Resection: A Case Report.

Functional reconstruction of the upper extremity has traditionally involved tendon transfer or pedicled muscle transfer. The gracilis free functional muscle transfer remains as an excellent option for restoration of finger flexion. Here, we provide a case report of a 35-year-old man diagnosed with left forearm high-grade epithelioid sarcoma who underwent innervated free gracilis transfer and a secondary free flap, the profunda artery perforator flap, through a single donor-site incision to expand soft tissue coverage. Postoperatively, there were no complications reported. At 8-month follow-up, the patient had Musculoskeletal Tumor Score of 22/30, and a Quick Disabilities of the Arm, Shoulder, and Hand score of 34/100.

Rapid detection of bacteria using gold nanoparticles in SERS with three different capping agents: Thioglucose, polyvinylpyrrolidone, and citrate.

The increase in outbreaks of emerging and re-emerging bacterial infections over the last few decades calls for their rapid detection and treatment. Surface-enhanced Raman spectroscopy (SERS) is a technique that can be applied to develop fast screening systems for bacterial presence in biological samples. Optimizing the capping agents in nanoparticle synthesis is important because capping agents are responsible for controlling the morphological features and chemical properties of the nanoparticles that are essential for SERS. To the best of our knowledge, this paper is the first to study the application of gold nanoparticles capped with thioglucose and polyvinylpyrrolidone (PVP) in SERS detection of bacteria as an alternative to the citrate-capped gold nanoparticles that are often used in SERS detection of bacteria. Three different species of bacteria were used in this study: Cutibacterium acnes, Escherichia coli and Staphylococcus aureus (methicillin-sensitive and methicillin-resistant). This study demonstrates that the thioglucose, citrate both show good contribution in bacterial species identification and the thioglucose shows the best among the three capping agents in two types of S. aureus identification. Moreover, although PVP showed high Raman peaks in the SERS spectrum for each type of bacteria, it showed least contribution in identifying species and strains due to its low efficacy in producing responses from different nucleic acid components in the bacteria cells.

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats : an animal study.

AIMS: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. METHODS: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. RESULTS: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. CONCLUSION: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9-16.

Combination Tests in the Diagnosis of Chronic Periprosthetic Joint Infection: Systematic Review and Development of a Stepwise Clinical Decision-Making Tool.

BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Does surgical approach influence mid- to long-term patient-reported outcomes after primary total hip replacement? A comparison of the 3 main surgical approaches.

Background: The most effective surgical approach to total hip replacement (THR) remains controversial. Most studies that have compared approaches have reported only short-term outcome data. It is therefore unclear in the literature if a particular surgical approach offers long-term advantages. The aim of this study was to determine the effect of the 3 main surgical approaches to THR on patient-reported outcomes 5 years after surgery. Methods: All patients who underwent a THR for osteoarthritis or osteonecrosis between 2008 and 2012 by an anterior, posterior or lateral approach at The Ottawa Hospital in Ontario, Canada, were included in the study. All preoperative and postoperative scores for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) questionnaires were recorded. Analysis of covariance was used to study the relationship between the amount of change in scores on the HOOS and WOMAC subscales (dependent variables) and the surgical approach. The confounding factors of age, sex, American Society of Anesthesiologists (ASA) class, Charnley classification and body mass index were included in the analysis. Results: There were 138 patients (37.6%) in the posterior approach group, 104 (28.3%) in the lateral approach group and 125 (34.1%) in the anterior approach group. There were no significant differences among the 3 groups in terms of Charnley classification, body mass index, sex, ASA class, surgical side and preoperative functional scores. We did not observe any significant differences in the amount of change in the scores for HOOS and WOMAC subscales among the 3 groups. There were also no differences in the final postoperative scores. Conclusion: Our findings suggest that the choice of surgical approach in primary THR surgery without revision has no influence on functional outcomes and quality of life after 5 years. Further studies are needed to assess how patient age and sex may influence the functional outcome of individual surgical approaches.

Contexte: L'approche chirurgicale la plus efficace pour l'arthroplastie totale de la hanche (ATH) n'a pas été déterminée. La plupart des études qui ont comparé les différentes approches n'ont fait état que de données à court terme. Donc, la littérature nous renseigne peu sur leurs bienfaits à long terme. Le but de cette étude est de vérifier l'effet des 3 principales approches chirurgicales pour l'ATH sur les paramètres rapportés par les patients 5 ans après la chirurgie. Méthodes: Tous les patients soumis à une ATH pour arthrose ou ostéonécrose entre 2008 et 2012 par approche antérieure, postérieure ou latérale à l'Hôpital d'Ottawa, en Ontario, au Canada, ont été inclus dans l'étude; et tous les scores préopératoires et postopératoires des questionnaires HOOS (Hip Disability and Osteoarthritis Outcome Score) et WOMAC (Western Ontario and MacMaster Universities Osteoarthritis Index) ont été enregistrés. L'analyse de covariance a servi à étudier le lien entre l'ampleur des changements aux scores des sous-échelles HOOS et WOMAC (variables dépendantes) et l'approche chirurgicale. L'analyse a aussi tenu compte de facteurs de confusion tels que l'âge, le sexe, la classe ASA (American Society of Anesthesiologists), classification de Charnley et indice de masse corporell. Résultats: Le groupe soumis à l'approche postérieure comptait 138 patients (37,6 %), à l'approche latérale 104 (28,3 %) et à l'approche antérieure 125 (34,1 %). Il n'y avait pas de différences significatives entre les 3 groupes aux plans de la classification de Charnley, de l'indice de masse corporelle, du sexe, de la classe ASA, du côté où la chirurgie a été effectuée et des paramètres fonctionnels préopératoires. Nous n'avons observé aucune différence significative quant à l'ampleur du changement aux scores des sous-échelles HOOS et WOMAC entre les 3 groupes; il en est allé de même pour les scores postopératoires finaux. Conclusion: Selon nos observations, le choix de l'approche chirurgicale pour l'ATH primaire sans révision n'exerce aucune influence sur les paramètres fonctionnels et la qualité de vie après 5 ans. Il faudra procéder à d'autres études pour évaluer l'influence potentielle de l'âge et du sexe sur les paramètres fonctionnels des différentes approches.

Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review.

BACKGROUND: Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. METHODS: This review adheres to the Cochrane Collaboration's diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. RESULTS: A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. CONCLUSIONS: The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

New Innovations in the Treatment of PJI and Biofilms-Clinical and Preclinical Topics.

PURPOSE OF REVIEW: Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement. A main source for antibiotic tolerance and treatment failure is bacterial production of biofilm-a resilient barrier against antibiotics, immune system, and mechanical debridement. The purpose of this review is to explore some novel approaches to treat PJI and biofilm-related infections. RECENT FINDINGS: Innovative treatment strategies of bacterial and biofilm infections revolve around (a) augmenting current therapies, such as improving the delivery and efficiency of conventional antibiotics and enhancing the efficacy of antiseptics and (b) administrating completely new therapeutic modalities, such as using immunotherapy, nanoparticles, lytic bacteriophages, photodynamic therapy, novel antibiotics, and antimicrobial peptides. Several promising treatment strategies for PJI are available to be tested further. The next requirement for most of the novel treatments is reproducing their effects in clinically representative animal models of PJI against clinical isolates of relevant bacteria.

Does Treatment Order Matter? Investigating the Ability of Bacteriophage to Augment Antibiotic Activity against Staphylococcus aureus Biofilms.

The inability to effectively treat biofilm-related infections is a major clinical challenge. This has been attributed to the heightened antibiotic tolerance conferred to bacterial cells embedded within biofilms. Lytic bacteriophages (phages) have evolved to effectively infect and eradicate biofilm-associated cells. The current study was designed to investigate the ability of phage treatment to enhance the activity of antibiotics against biofilm-forming Staphylococcus aureus. The biofilm positive S. aureus strain ATCC 35556, the lytic S. aureus phage SATA-8505, and five antibiotics (cefazolin, vancomycin, dicloxacillin, tetracycline, and linezolid), used to treat S. aureus infections, were tested in this study. The ability of the SATA-8505 phage to augment the effect of these antibiotics against biofilm-associated S. aureus cells was assessed by exposing them to one of the five following treatment strategies: (i) antibiotics alone, (ii) phage alone, (iii) a combination of the two treatments simultaneously, (iv) staggered exposure to the phage followed by antibiotics, and (v) staggered exposure to antibiotics followed by exposure to phage. The effect of each treatment strategy on biofilm cells was assessed by enumerating viable bacterial cells. The results demonstrate that the treatment of biofilms with either SATA-8505, antibiotics, or both simultaneously resulted in minimal reduction of viable biofilm-associated cells. However, a significant reduction [up to 3 log colony forming unit (CFU)/mL] was observed when the phage treatment preceded antibiotics. This effect was most pronounced with vancomycin and cefazolin which exhibited synergistic interactions with SATA-8505, particularly at lower antibiotic concentrations. This in vitro study provides proof of principle for the ability of phages to augment the activity of antibiotics against S. aureus biofilms. Our results also demonstrate that therapeutic outcomes can be influenced by the sequence in which these therapeutic agents are administered, and the nature of their interactions. Further investigation into the interactions between lytic phages and antibiotics against various biofilm-forming organisms is important to direct future clinical translation of efficacious antibiotic-phage combination therapeutic strategies.

Tertiary care centre adherence to unified guidelines for management of periprosthetic joint infections: a gap analysis.

BACKGROUND: The success rate of surgical treatment for periprosthetic joint infection (PJI) remains inconsistent in the literature. Variability in PJI clinical guidelines and surgeon adherence to guidelines could affect treatment success. The objectives of this study were to appraise current recommendations for PJI management and develop a unified clinical standard of care, to perform a gap analysis of PJI cases in a tertiary institution to determine the rate of guideline adherence, and to determine if adherence to unified PJI guidelines affected 2-year treatment outcomes. METHODS: We appraised the PJI guidelines from 3 academic medical societies, and consistent statements were aggregated. We retrospectively reviewed all PJI cases in a tertiary care institution. We defined PJI based on Musculoskeletal Infection Society PJI criteria. Surgeon adherence to preoperative, intraoperative, surgical and medical management guidelines was calculated, and we evaluated the association between guideline adherence and 2-year treatment outcomes. RESULTS: The institutional rate of PJI was 1.13% (38 of 3368). Treatment success was 57.8% at 2 years. Unified guideline adherence percentages varied substantially: 92% of patients had preoperative erythrocyte sedimentation rate and C-reactive protein, 97% had intraoperative tissue cultures, 42% had appropriate preoperative arthrocentesis, and 74% underwent guideline-appropriate surgery. Performing appropriate preoperative arthrocentesis significantly correlated with positive treatment outcomes at 2 years (p = 0.028). CONCLUSION: Adherence to PJI guidelines varies considerably, indicating that clinicians are either unaware of them or do not recognize their value for PJI treatment. This study shows the need for institution-based PJI treatment pathways that are consistent with published guidelines and the need to monitor adherence.

CONTEXTE: Les études ne concordent pas quant au taux de réussite du traitement chirurgical des infections de prothèses articulaires (IPA). Une certaine variabilité dans les lignes directrices sur ces infections et dans l'adhésion des chirurgiens à celles-ci pourrait nuire à la réussite du traitement. La présente étude visait à évaluer les recommandations actuelles sur la prise en charge des IPA afin d'élaborer une norme de soins uniforme, à effectuer une analyse des lacunes entourant les cas d'IPA dans un établissement de soins tertiaires pour déterminer le taux d'adhésion aux lignes directrices, et à déterminer si l'adhésion à des lignes directrices uniformes influençait les issues de traitement après 2 ans. MÉTHODES: Nous avons évalué les lignes directrices sur les IPA de 3 sociétés médicales universitaires, et agrégé des énoncés cohérents. Nous avons également examiné de façon rétrospective tous les cas d'IPA dans un établissement de soins tertiaires. Aux fins de notre étude, l'IPA était définie selon les critères de la Musculoskeletal Infection Society. Nous avons calculé l'adhésion des chirurgiens aux lignes directrices de prise en charge préopératoire, peropératoire, chirurgicale et médicale, puis nous avons évalué l'association entre ce paramètre et les issues de traitement après 2 ans. RÉSULTATS: Le taux d'IPA dans l'établissement était de 1,13 % (38 sur 3368), et le taux de réussite du traitement était de 57,8 % après 2 ans. Les pourcentages d'adhésion aux lignes directrices variaient considérablement : 92 % des patients avaient eu une analyse préopératoire de la vitesse de sédimentation érythrocytaire et de la protéine C-réactive, 97 % avaient eu des cultures tissulaires peropératoires, 42 % avaient eu une arthrocentèse préopératoire appropriée, et 74 % avaient subi une intervention chirurgicale conforme aux lignes directrices. Il y avait une corrélation significative entre l'arthrocentèse préopératoire et les issues favorables après 2 ans (p = 0,028). CONCLUSION: L'adhésion aux lignes directrices sur les IPA varie considérablement, ce qui indique que les cliniciens ne les connaissent pas ou n'en reconnaissent pas la valeur pour le traitement des IPA. La présente étude montre qu'il faut dans les établissements des protocoles de traitement conformes aux lignes directrices publiées, et qu'il est nécessaire de surveiller l'adhésion des chirurgiens à celles-ci.

Current review-The rise of bacteriophage as a unique therapeutic platform in treating peri-prosthetic joint infections.

Peri-prosthetic joint infection (PJI) is one of the most serious and dreaded complications after total joint replacement (TJR). Due to an aging population and the constant rise in demand for TJR, the incidence of PJI is also increasing. Successful treatment of PJI is challenging and is associated with high failure rates. One of the main causes for treatment failure is bacterial biofilm formation on implant surfaces and the adherence of biofilm bacteria on tissue and bone next to the implant. Biofilms are protective shields to bacterial cells and possess many unique properties that leads to antibiotic resistance. New therapeutic platforms are currently being explored to breakdown biofilm matrix in order to enhance the efficacy of antibiotics. Bacteriophages (phages) is one of these unique therapeutic platforms that can degrade biofilms as well as target the killing of bacterial cells. Preclinical studies of biofilm-mediated infections have demonstrated the ability of phage to eradicate biofilms and clear infections by working synergistically with antibiotics. There is strong preclinical evidence that phage can reduce the concentration of antibiotics required to treat an infection. These findings support a promising role for phages as a future clinical adjunct to antibiotics. In addition, phage therapy can be personalized to target a specific bacterial strain. Clinical studies using phage therapy are limited in Western literature; but phase I studies have established good safety profile with no adverse outcomes reported. In order to translate phage therapy to treat PJI in clinics, further preclinical testing is still required to study optimal delivery methods as well as the interaction between phage and the immune system in vivo. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1051-1060, 2018.

Oncolytic Maraba Virus MG1 as a Treatment for Sarcoma.

The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre-clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side-by-side comparison of clinically relevant OV platforms has not been performed. Four clinically relevant OV platforms (Reovirus, Vaccinia virus, Herpes-simplex virus and Rhabdovirus) were screened for their ability to infect and kill human and canine sarcoma cell lines in vitro, and human sarcoma specimens ex vivo. In vivo treatment efficacy was tested in a murine model. The rhabdovirus MG1 demonstrated the highest potency in vitro. Ex vivo, MG1 productively infected more than 80% of human sarcoma tissues tested, and treatment in vivo led to a significant increase in long-lasting cures in sarcoma-bearing mice. Importantly, MG1 treatment induced the generation of memory immune response that provided protection against a subsequent tumor challenge. This study opens the door for the use of MG1-based oncolytic immunotherapy strategies as treatment for sarcoma or as a component of a combined therapy.