Upcoming evidence in clinical practice of two-stage revision arthroplasty for prosthetic joint infection.

Total joint arthroplasty is the recommended treatment for patients with end-stage osteoarthritis, as it reduces disability and pain and restores joint function. However, prosthetic joint infection is a serious complication of this procedure, with the two-stage exchange being the most common treatment method. While there is consensus on diagnosing prosthetic joint infection, there is a lack of agreement on the parameters that can guide the surgeon in performing definitive reimplantation in a two-stage procedure. One approach that has been suggested to improve the accuracy of microbiologic investigations before definitive reimplantation is to observe a holiday period from antibiotic therapy to improve the accuracy of cultures from periprosthetic tissues, but these cultures report some degree of aspecificity. Therefore, several pieces of evidence highlight that performing reimplantation using continuous antibiotic therapy should be considered a safe and effective approach, leading to higher cure rates and a shorter period of disability. Dosage of C-reactive protein (CRP), erythrocyte sedimentation rate (ERS) and D-dimer are helpful in diagnosing prosthetic joint infection, but only D-dimer has shown sufficient accuracy in predicting the risk of infection recurrence after a two-stage procedure. Synovial fluid analysis before reimplantation has been shown to be the most accurate in predicting recurrence, and new cutoff values for leukocyte count and neutrophil percentage have shown a useful predictive rule to identify patients at risk of unfavourable outcome. A new scoring system based on a numerical score calculated from the beta coefficient derived through multivariate analysis of D-dimer levels, synovial fluid leukocytes and relative neutrophils percentage has demonstrated high accuracy when it comes to guiding the second step of two-stage procedure. In conclusion, reimplantation may be a suitable option for patients who are on continuous therapy without local symptoms, and with CRP and ERS within the normal range, with low synovial fluid leukocytes (< 952/mL) and a low relative neutrophil percentage (< 52%) and D-dimer below 1100 µg/mL. A numerical score derived from analysing these three parameters can serve as a valuable tool in determining the feasibility of reimplantation in these patients.

Augmented Articulating Spacers in Infected Total Knee Arthroplasty: Surgical Technique.

Periprosthetic joint infections (PJIs) are a prominent subject of discussion in orthopedics and are frequently debated at conferences and congresses. In the context of PJIs affecting the knee, the decision between following a one-stage or two-stage treatment approach has historically been a pivotal consideration. The first option is limited by indications and potentially devastating complications in case of failure, whereas the second is widely accepted as the gold standard. Initially, the spacer was conceived solely to restore and maintain knee space after removal of the implant. An articulating spacer was introduced to mitigate patient limitations and improve knee function and quality of life. Two main types of articulating spacers are utilized in knee PJI treatment: the mold spacer and the metal-on-poly spacer. This text outlines a technique for metal-on-poly spacer implants. Based on our experience and the existing literature, this approach facilitates early full weight bearing and faster recovery of the knee's range of motion, ultimately improving the quality of life after surgery, thus allowing the spacer retention for an extended period, as suggested by the 1.5-stage revision.

Ideal Timing of Reimplantation in Patients with Periprosthetic Knee Infection Undergoing 2-Stage Exchange: A Diagnostic Scoring System.

BACKGROUND: This study evaluated appropriate thresholds for serum biomarkers, synovial fluid white blood cell (SF-WBC) count, and synovial fluid neutrophil (polymorphonuclear leukocyte [PMN]) percentage to predict infection in a patient group who underwent definitive reimplantation after receiving a continuous course of antibiotic therapy for chronic knee periprosthetic joint infection (PJI). These thresholds were then used to generate a scoring system to predict recurrence (or persistence) of infection. METHODS: The study included 153 patients with a median age of 73 years (range, 46 to 91 years) who underwent 2-stage revision for chronic knee PJI. Staphylococci were identified at baseline in 107 (70%) of the patients. After the 96-week follow-up period, 12% (19) of the 153 patients had recurrence of the PJI. A receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of common serum biomarkers and SF aspiration before reimplantation, and the area under the curve (AUC) was evaluated. Variables that were significantly different between patients with and without infection recurrence were evaluated using a multivariable logistic regression model. A half-integer-point scoring system was created based on the final beta coefficients. RESULTS: Regarding the prediction of recurrent infection, a D-dimer level of >1110 ng/mL yielded a sensitivity of 74%, specificity of 61%, and AUC of 0.69; an SF-WBC count of >934 cells/µL showed a sensitivity of 68%, specificity of 90%, and AUC of 0.79; and an SF-PMN percentage of >52% showed a sensitivity of 73%, specificity of 90%, and AUC of 0.82. The beta coefficients were approximated to 1.5 for the D-dimer level and to 2 for the SF-WBC count and SF-PMN percentage. A total score of >2 was used to classify patients with a high risk of infection recurrence. The ability to discriminate infection recurrence was demonstrated by an AUC of 0.90 (95% confidence interval: 0.82 to 0.99). CONCLUSIONS: Patients with a score of >2 on our proposed scoring system based on serum biomarkers, SF-WBC count, and SF-PMN percentage should not undergo reimplantation, as they are at a high risk for recurrent PJI. Patients with a score of ≤2 can undergo definitive reimplantation with the lowest risk of recurrence. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Barbed sutures and skin adhesives improve wound closure in hip and knee arthroplasty.

PURPOSE: This study aimed to formulate evidence-based recommendations for optimising wound management in hip and knee arthroplasty by exploring alternative methods such as barbed sutures and skin adhesives. METHODS: A Delphi panel, comprising seven orthopaedic surgeons, one musculoskeletal infectious disease specialist, and one health economics expert, was convened to evaluate the use of barbed sutures and skin adhesives for wound closure in hip and knee arthroplasty. Two systematic reviews informed the development of questionnaires, with panelists ranking their agreement on statements using a 5-point Likert scale. Consensus was achieved if ≥75% agreement. Unresolved statements were revisited in a second round. RESULTS: Consensus was reached on 11 statements, providing evidence-based recommendations. The expert panel advocates for a multilayer watertight technique using barbed sutures to prevent surgical site infections (SSI), reduce complications, shorten surgical times, optimise resources and improve cosmetic appearance. For skin closure, the panel recommends topical adhesives to decrease wound dehiscence, enhance cosmetic appearance, promote patient compliance, prevent SSIs, and optimise resources. CONCLUSION: The Delphi consensus by Italian total joint arthroplasty experts underscores the pivotal role of barbed sutures and skin adhesives in optimising outcomes. While guiding clinical decision-making, these recommendations are not prescriptive and should be adapted to local practices. The study encourages further research to enhance current evidence. LEVEL OF EVIDENCE: Level III.

Synovial fluid alpha-defensin in periprosthetic knee infection workup : liquid chromatography-mass spectrometry detection of alpha-defensin in synovial fluid.

AIMS: The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid. METHODS: Between October 2017 and September 2019, we collected synovial fluid samples from patients scheduled to undergo revision surgery for painful total knee arthroplasty (TKA). The International Consensus Meeting criteria were used to classify 33 PJIs and 92 aseptic joints. LC-MS assay was performed to measure alpha-defensin in synovial fluid of all included patients. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) were calculated to define the test diagnostic accuracy. RESULTS: The AUC was 0.99 (95% confidence interval (CI) 0.98 to 1.00). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off value of synovial fluid alpha-defensin was 1.0 µg/l. The sensitivity of alpha-defensin was 100% (95% CI 96 to 100), the specificity was 97% (95% CI 90 to 98), the positive predictive value was 89.2% (95% CI 82 to 94), and negative predictive value was 100% (95% CI 96 to 100). ROC analysis demonstrated an AUC of 0.99 (95% CI 0.98 to 1.0). CONCLUSION: The present study confirms the utility of alpha-defensin in the synovial fluid in patients with painful TKA to select cases of PJI. Since LC-MS is still a time-consuming technology and is available in highly specialized laboratories, further translational research studies are needed to take this evidence into routine procedures and promote a new diagnostic approach.Cite this article: Bone Joint J 2022;104-B(9):1047-1051.

An overview of the preclinical discovery and development of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

INTRODUCTION: Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. AREAS COVERED: In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. EXPERT OPINION: RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.

Management of septic arthritis of the hip joint in adults. A systematic review of the literature.

BACKGROUND: The septic arthritis of the hip is a complex condition characterized by a variety of clinical presentations, a challenging diagnosis and different surgical treatment options, including arthroscopy, resection arthroplasty and one and two-stage total hip replacement. Each technique reports variable results in terms of infection eradication rate. The aim of this systematic review is to compare the most relevant studies available in current literature and to assess if a better treatment outcome can be predicted based on the microbiology, history, and type of infection (active vs quiescent) of each case. METHODS: A systematic review of the literature was performed in accordance with the PRISMA guidelines, including the studies dealing with the treatment of hip septic arthritis in adult patients. Electronic databases, namely the MEDLINE, Scopus, and Web of Science, were reviewed using a combination of following keywords "septic arthritis" AND "hip joint" OR "hip" AND "adult". RESULTS: The total number of patients included in this review was 1236 (45% of which females), for 1238 hips. The most common pathogen isolated was Staphylococcus aureus in its Methicillin-sensitive variant ranging from 2 to 37% of cases. Negative cultures were the second most common finding. It was also differentiated the type of infection of the hip, 809 and 417 patients with active and quiescent hip infection, respectively, were analyzed. Eradication rates for two-stage revision arthroplasty ranged between 85 and 100%, for one-stage approach between 94 and 100%, while for arthroscopic debridement/lavage between 89 and 100%. CONCLUSION: Staphylococcus aureus is the most common microorganism isolated followed by culture negative infections. Arthroscopic, one and two stage procedures can be effective in the treatment of hip septic arthritis when the indication is consistent with the type of infection retrieved. LEVEL OF EVIDENCE: IV, therapeutic study.

Synovial Cell Count Before Reimplantation Can Predict the Outcome of Patients with Periprosthetic Knee Infections Undergoing Two-stage Exchange.

BACKGROUND: Although synovial fluid can be used to diagnose periprosthetic joint infections (PJI) effectively, only the cutoff values adopted at the time of PJI diagnosis have been standardized, and few data are currently available about effectiveness of synovial fluid examination before definitive reimplantation. QUESTIONS/PURPOSES: We asked: (1) What are the most appropriate thresholds for synovial fluid leukocyte counts (WBC) and neutrophil percentage (PMN percentage) in a patient group undergoing definitive reimplantation after an uninterrupted course of antibiotic therapy for chronic PJI? (2) What is the predictive value of our synovial WBC and PMN percentage threshold compared with previously proposed thresholds? METHODS: In all, 101 patients with PJI were evaluated for inclusion from January 2016 to December 2018. Nineteen percent (19 of 101) of patients were excluded because of the presence of a chronic inflammatory disease, acute/late hematogenous infection, low amount of synovial fluid for laboratory investigations or infection persistence after spacer placement, and adequate antibiotic therapy. Finally, 81% (82 of 101) of patients with a median (range) age of 74 years (48 to 92) undergoing two-stage revision for chronic TKA infection, who were followed up at our institution for a period 96 weeks or more, were included in this study. The patients did not discontinue antibiotic treatment before reimplantation and were treated for 15 days after reimplantation if intraoperative cultures were negative. No patient remained on suppressive treatment after reimplantation. Synovial fluid was aspirated aseptically with a knee spacer in place to evaluate the cell counts before reimplantation. Thirteen percent (11 of 82) of patients had persistent or recurrent infection, defined as continually elevated erythrocyte sedimentation rate or C-reactive protein levels coupled with local signs and symptoms or positive cultures. The synovial fluid WBC counts and PMN percentage from the 11 patients with persistent or recurrent PJI were compared with the 71 patients who were believed to be free of PJI. Receiver operating characteristic (ROC) curve analyses assessed the predictive value of the parameters, and the areas under the curves (AUCs) were evaluated. The sensitivities, specificities, and positive and negative predictive values were determined for the WBC count and PMN percentage. Patients with persistent or recurrent infection had higher median WBC counts (471 cells/µL versus 1344 cells/µL; p < 0.001) and PMN percentage (36% versus 61%; p < 0.001) than did patients believed to be free of PJI. RESULTS: ROC curve analysis identified the best threshold values to be a WBC count of 934 cells/µL or more (sensitivity 0.82 [95% CI 0.71 to 0.89], specificity 0.82 [95% CI 0.71 to 0.89]) as well as a PMN percentage of at least 52% (sensitivity 0.82 [95% CI 0.71 to 0.89] and specificity 0.78 [95% CI 0.67 to 0.86]. We found no difference between the AUCs for the WBC count and the PMN percentage (0.87 [95% CI 0.79 to 0.96] versus 0.84 [95% CI 0.73 to 0.95]. Comparing the sensitivities and specificities of the synovial fluid WBC count and PMN percentage proposed by other authors, we find that a PMN percentage more than 52% showed better predictive value than previously reported. CONCLUSION: Based on our findings, we believe that patients with WBC counts of at least 934 and PMN percentage of 52% or more should not undergo reimplantation but rather a repeat debridement, as their risk of persistent or recurrent PJI appears prohibitively high. The accuracy of the proposed cutoffs is better than previously reported. LEVEL OF EVIDENCE: Level III, diagnostic study.

An Evolution of Shoulder Periprosthetic Infections Management: MicroDTTect, Bioactive Glass and Tantalum Cones Employment.

Periprosthetic joint infections of the shoulder (PJIS) are the major cause for revision within the first two post-operative years, and are challenging both to diagnose and treat. Success depends on early identification of microorganisms, appropriate surgical procedures and efficient antibiotic administration. The peculiar microbiology of the shoulder may render the criteria for hip/knee PJI management inappropriate. In addition, later cases with clinically subtle signs often present diagnostic challenges. In recent years, specific issues of PJIS have been managed through the use of new instruments, such as MicroDTTect in pathogen detection and Bioactive Glass and tantalum cones in humeral bone loss. In the literature to date, no reports have been found that discuss the application in shoulder revisions and infections. The early identification of the microorganisms that cause infection may help improve both treatment strategies and the efficacy of therapy. MicroDTTect proved to be more efficient than swab collection for bacterial identification in orthopedic surgery, thus reducing analysis costs. The increasing number of shoulder arthroplasties is associated with an increase in the number of revisions. In cases of massive metaphyseal humeral bone loss, several techniques have been described; no reports have been reported regarding tantalum in humeral bone loss management. In some cases the tantalum cones required adaptation for femoral diaphysis in the augmentation of the humerus metaphysis and bone loss management improvement. Obtaining stable osseointegration of prosthetic implants is one of the greatest issues in orthopedic surgery, and even more crucial in revisions. Bioactive glasses demonstrated good regenerative and osseointegration properties, and an excellent candidate as a bone graft, scaffold and antibiotics deliverer. The Bioactive glasses were used to increase prosthesis-bone interface stability and fill bone defects in PJIS revision surgeries, contributing to the prevention of re-infection. Longer-term follow-up will be necessary to determine if construction durability is improved in the long term.

Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis.

INTRODUCTION: Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS: We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated. RESULTS: We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83-0.94) and 0.95 (0.92-0.96), respectively. The area under the curve (AUC) was 0.94 (0.92-0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93-0.99) and 0.96 (95% CI 0.94-0.98), respectively; qualitative test 0.83 (95% CI 0.73-0.91) and 0.94 (95% CI 0.89-0.97), respectively. The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172-3600.702 versus 100.9, 95% CI 30.1-338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95-0.99) and 0.91 (0.88-0.99), respectively. CONCLUSION: Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

Knee septic arthritis caused by α-hemolytic Streptococcus in a patient with a recent history of knee arthroscopy: a case report.

BACKGROUND: Arthroscopic partial meniscectomy is a common procedure in orthopedic practice. Infections are uncommon complications of this procedure with an incidence rate of 0,01% - 3,4%. Staphylococcus spp are the predominant causative agents in such cases. We present a case of knee septic arthritis caused by α-hemolytic Streptococcus. CASE PRESENTATION: A 22-year-old woman diagnosed with obesity (body mass index [BMI] 35 kg/m2) but with no other major comorbidities underwent an arthroscopic selective meniscectomy with administration of intravenous cefazolin for antibiotic prophylaxis. After an uneventful period of 2 months, the patient returned with pain, fever and a discharging sinus at the site of anterolateral arthroscopic portal. Blood tests and magnetic resonance imaging revealed osteomyelitis involving the tibial plate. Cultures of synovial fluid obtained from the knee and a pharyngeal swab yielded α-hemolytic Streptococcus. Five days later, the patient underwent arthroscopic debridement with partial synovectomy. Intraoperative specimens yielded α-hemolytic Streptococcus. The patient received intravenous piperacillin/tazobactam, followed by an associative regimen of amoxicillin and clindamycin with clinical, laboratory and instrumental evidence of symptom resolution. CONCLUSION: The incidence of knee septic arthritis after arthroscopic partial meniscectomy is 0.01-3.4%. This infection is usually caused by Staphylococcus spp. and in rare cases by commensal bacteria, such as α-hemolytic streptococci, secondary to transient bacteremia. Screening of the colonized area is important to prevent possible transient bacteremia. Diagnosis is based on isolation of the causative organisms from synovial fluid cultures, and treatment comprises arthroscopic debridement with individualized systemic antibiotic therapy based on the results of an antibiogram.

Continuous Antibiotic Therapy Can Reduce Recurrence of Prosthetic Joint Infection in Patients Undergoing 2-Stage Exchange.

BACKGROUND: Reimplantation microbiology and serum C-reactive protein have low diagnostic accuracy in predicting recurrence in patients with prosthetic joint infection (PJI) undergoing 2-stage exchange. We aimed at identifying factors relating to failure and comparing effect of continuous antibiotic therapy versus a holiday antibiotic period pre-reimplantation. METHODS: This observational study included patients with PJI undergoing 2-stage exchange. Group A patients did not discontinue antibiotic treatment pre-reimplantation; in group B patients, antibiotic treatment was followed with 2 weeks of holiday antibiotic period pre-reimplantation. We defined cure as absence of recurrence for 96 weeks post-reimplantation. Statistical analyses were performed using Mann-Whitney U test, Fisher exact test, and multivariate analysis. RESULTS: We evaluated 196 patients with PJI (median age, 66 years [interquartile range, 59-72], 91 [46%] males). Comorbidity was reported in 77 (39%), and microbiologic evidence was obtained in 164 (84%). Staphylococcus aureus was isolated in 63 of 164 (38%) patients; coagulase-negative staphylococci were isolated in 71 of 164 (43%). Favorable outcome was achieved for 169 (86%) patients (91% and 79% in groups A and B, respectively). No immunocompromise (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.3-7.3; P = .04), a positive culture (OR, 3.96; 95% CI, 1.55-10.19; P = .02), and no antibiotic discontinuation (OR, 3.32; 95% CI, 1.3-8.44; P = .02) predicted favorable outcome using multivariate analysis. CONCLUSION: Treatment with continuous antibiotic therapy ameliorated success rate, permitting a better outcome in immunocompromised and reducing the time to reimplantation. Continuous antibiotic therapy can be considered a valid option for the treatment of patients with PJI undergoing 2-stage exchange. LEVEL OF EVIDENCE: Therapeutic level II.

Bacterial biofilm formation is variably inhibited by different formulations of antibiotic-loaded bone cement in vitro.

PURPOSE: The aim of the present study was to quantitatively assess biofilm growth on the surface of bone cements discs containing different antibiotics, including colistin and linezolid. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Staphylococcus epidermidis were grown on bone cement discs for 96 h. METHODS: Biofilm amounts were measured by confocal laser microscopy using live/dead staining and dedicated software at different time intervals (48, 72, and 96 h). RESULTS: Bone cement containing vancomycin was not effective at reducing MRSA biofilm formation 96 h following bacterial inoculation. At a comparable time interval, linezolid-, clindamycin-, and aminoglycoside-loaded cement was still active against this biofilm. At the 72- and 96-h observations, S. epidermidis biofilm was present only on tobramycin and gentamicin discs. P. aeruginosa biofilms were present on cement discs loaded with colistin at all time intervals starting from the 48-h observation, whereas no biofilms were detected on tobramycin or gentamicin discs. CONCLUSION: Bone cements containing different antibiotics have variable and time-dependent windows of activity in inhibiting or reducing surface biofilm formation. The effectiveness of bone cement containing vancomycin against MRSA biofilm is questionable. The present study is clinically relevant, because it suggests that adding the right antibiotic to bone cement could be a promising approach to treat periprosthetic infections. Indeed, the antibiofilm activity of different antibiotic-loaded bone cements could be preoperatively assessed using the current methodology in two-stage exchange procedures.

Re-infection rates and clinical outcomes following arthrodesis with intramedullary nail and external fixator for infected knee prosthesis: a systematic review and meta-analysis.

BACKGROUND: Knee arthrodesis with intramedullary (IM) nail or external fixator (EF) is the most reliable therapeutic option to achieve definitive infection control in patients with septic failure of total knee arthroplasty (TKA). The first aim of this study was to compare re-infection rates following knee arthrodesis for periprosthetic joint infection (PJI) with IM nail or EF. The second aim was to compare rates of radiographic union, complication, and re-operation as well as clinical outcomes. METHODS: A systematic search was performed in electronic databases for longitudinal studies of PJIs (minimum ten patients; minimum follow-up = 1 year) treated by knee arthrodesis with IM nail or EF. Studies were also required to report the rate of re-infection as an outcome measure. Eligible studies were meta-analyzed using random-effect models. RESULTS: The rate (95% confidence intervals) of re-infection was 10.6% (95% CI 7.3 to 14.0) in IM nail arthrodesis studies. The corresponding re-infection rate for EF was 5.4% (95% CI 1.7 to 9.1). This difference was significant (p = 0.009). The use of IM nail resulted in more advantages than EF for frequency of major complications and limb shortening. Other postoperative clinical and radiographic outcomes were similar for both surgical strategies. CONCLUSIONS: The available evidence from the aggregate published data suggests that knee arthrodesis with EF in the specific context of PJI has a reduced risk of re-infection in comparison with the IM nail strategy. The use of IM nail is more effective for the complication rate and shortening of the affected limb.

High performance of α-defensin lateral flow assay (Synovasure) in the diagnosis of chronic knee prosthetic infections.

PURPOSE: This prospective study was undertaken to evaluate the diagnostic accuracy of the Synovasure™ α-defensin lateral flow assay to detect or exclude infection and to compare it to the sensitivity and specificity of other diagnostic criteria according to the International Consensus Group on Periprosthetic Joint Infection (PJI). METHODS: All patients who have undergone revision total knee arthroplasty (TKA) from September 2015 to July 2016 were included: 16 chronic (more than 3 months after performing arthroplasty) infections and 35 aseptic joints were identified. The diagnostic performance of single test was assessed by receiver operating characteristic (ROC) curve analyses. The sensitivity and specificity were calculated for each of the cut-off values and the area under the curve (AUC) was also calculated. RESULTS: The median synovial fluid (SF) leukocyte count, as well as the neutrophil percentage, was significantly higher in patients with PJI than in those with aseptic failure (p < 0.001). The sensitivity of α-defensin was 87.5% (95%; CI 74.6-94.7), the specificity was 97.1% (95% CI 86.9-99.7), the positive predictive value 93.3% (95% CI 81.8-98.1), and negative predictive value was 94.4% (95% CI 83.2-98.6). The results in terms of sensitivity and negative predictive value were greater than those of the other tests (cultures, synovial cell count, erythrocyte sedimentation rate, and C-reactive protein). The diagnostic accuracy of α-defensin, with an area under the curve of 0.92, was found to be higher than all the minor criteria for PJI. CONCLUSIONS: In this study, the α-defensin lateral flow test was found to have the highest performance of all tests studied to identify PJI. Synovasure™ holds the potential to be included in the daily clinical practice. LEVEL OF EVIDENCE: Level I diagnostic study.

Diagnostic accuracy of synovial fluid, blood markers, and microbiological testing in chronic knee prosthetic infections.

INTRODUCTION: This retrospective study was undertaken to define cut-off values for synovial fluid (SF) leukocyte count and neutrophil percentage for differentiating aseptic failure and periprosthetic joint infection (PJI) and to evaluate the diagnostic accuracy of blood inflammatory markers, and microbiological testing according to the criteria proposed by the International Consensus Meeting (ICM) of Philadelphia. METHODS: All patients who underwent revision total knee arthroplasty from January 2010 to July 2015 were included: we identified and classified 31 PJIs and 136 aseptic joints. The diagnostic performance of single test was assessed by receiver operating characteristic curve analyses. The sensitivity and specificity were calculated for each of the cut-off values and the area under the curve (AUC) was calculated. RESULTS: The median SF leukocyte count as well as the neutrophil percentage and inflammatory markers were significantly higher in patients with PJI than in those with aseptic failure (p < 0.001). A leukocyte count of > 2.8 × 103/µL had a sensitivity of 83.8% and a specificity of 89.7% whereas a neutrophil percentage of > 72% yielded a marginally higher sensitivity of 84% and a specificity of 91%. Applying the ICM criteria we found a significant correlation between all these diagnostic measures and PJI (p < 0.001) except for a single positive culture. The most accurate criterion of the ICM was the synovial neutrophil differential (AUC = 0.89; 95% CI 0.81-0.97), followed by SF leukocyte count (AUC = 0.86; 95% CI 0.78-0.94), increased inflammatory markers (AUC = 0.85; 95% CI 0.76-0.93), and two positive periprosthetic cultures (AUC = 0.84; 95% CI 0.73-0.94). The presence of sinus tract communicating with the joint and a single positive culture showed unfavourable diagnostic accuracy (AUC = 0.60, 95% CI 0.47-0.72; AUC = 0.49, 95% CI 0.38-0.61, respectively) CONCLUSIONS: The present study highlights the adequate ability of fluid cell count and neutrophil differential to distinguish between PJI and aseptic loosening. The clinical utility of fluid analysis in diagnosing infection can be improved by evaluation of other diagnostic criteria. LEVEL OF EVIDENCE: Level I Diagnostic Study.

Epidemiology and treatment of the commonest form of listeriosis: meningitis and bacteraemia.

Listeria monocytogenes is a Gram-positive bacillus and facultative intracellular bacterium whose transmission occurs mainly through the consumption of contaminated food. Listeriosis has an incidence estimated at around three-six cases per million per year and the most common forms of the infection are neurolisteriosis, bacteraemia, and maternal-neonatal infection. Those affected by listeriosis are at the extremes age of the life or report specific risk factors, such as malignancies, causing a defect of cellular immunity. Patients with L. monocytogenes meningitis present with signs and symptoms similar to those reported in the general population with community-acquired bacterial meningitis, but can experience a longer prodromal phase. Instead, patients with bacteraemia present generally with a febrile illness without focal symptoms, or with influenza-like symptoms and diarrhoea. These aspecific findings make the diagnosis difficult in the population of patients at the highest risk such as cirrhotics or those receiving chemotherapy. Mortality rate is estimated around 20% with a significant increase among those reporting a delay in diagnosis and treatment and in those with severe comorbidity. A number of antibiotics have been demonstrated to be active against L. monocytogenes, but penicillin, amoxicillin, and ampicillin are those used with the highest frequency and suggested by current guidelines and expert opinions. These antibiotics bind to PBP-3 with high affinity and are stored in the cytosol when taken up by cells. Although amoxicillin appears to have a better activity than ampicillin on the basis of in vitro studies, ampicillin is currently the drug of choice for the treatment of listeriosis. Cotrimoxazole could be administered as an alternative treatment; its use is associated with a favourable outcome probably due to the favourable penetration with brain. Quinolones have an excellent tissue and cell penetration and are rapidly bactericidal, but their clinical activity is not as high as we can predict on the basis of experimental model. Linezolid offers a number of advantages in the empiric treatment of meningitis due to its favourable penetration of CSF and the absence of bacteriolytic effect on S. pneumoniae as confirmed by a number of case-series highlighting its use as rescue therapy of pneumococcal meningitis, but data are currently limited particularly if we consider neurolisteriosis. Combination therapies have been proposed to enhance the activity of penicillins against Listeria in an attempt to achieve complete killing and decrease mortality. Steroids use is ineffective.

Characteristics of meningitis following transsphenoidal endoscopic surgery: a case series and a systematic literature review.

BACKGROUND: Meningitis occurs in 0.8-1.5% of patients undergoing neurosurgery. The aim of the study was to evaluate the characteristics of meningitis after endoscopic endonasal transsphenoidal surgery (EETS) comparing the findings retrieved to those highlighted by literature search. MATERIALS AND METHODS: Patients treated by EETS during an 18-year period in the Department of Neurosurgery of 'Federico II' University of Naples were evaluated and included in the study if they fulfilled criteria for meningitis. Epidemiological, demographic, laboratory, and microbiological findings were evaluated. A literature research according to PRISMA methodology completed the study. RESULTS: EETS was performed on 1450 patients, 8 of them (0.6%) had meningitis [median age 46 years (range 33-73)]. Endoscopic surgery was performed 1-15 days (median 4 days) before diagnosis. Meningeal signs were always present. CSF examination revealed elevated cells [median 501 cells/µL (range 30-5728)], high protein [median 445 mg/dL (range 230-1210)], and low glucose [median 10 mg/dL (range 1-39)]. CSF culture revealed Gram-negative bacteria in four cases (Klebsiella pneumoniae, Escherichia coli, Alcaligenes spp., and Haemophilus influenzae), Streptococcus pneumoniae in two cases, Aspergillus fumigatus in one case. An abscess occupying the surgical site was observed in two cases. Six cases reported a favorable outcome; two died. Incidence of meningitis approached to 2%, as assessed by the literature search. CONCLUSIONS: Incidence of meningitis after EETS is low despite endoscope goes through non-sterile structures; microorganisms retrieved are those present within sinus microenvironment. Meningitis must be suspected in patients with persistent fever and impaired conscience status after EETS.