This study aimed to evaluate the effectiveness and safety of intra-articular vancomycin powder in reducing prosthetic joint infections (PJIs) in primary hip and knee arthroplasty through a meta-analysis of randomized controlled trials (RCTs).

A research in Pubmed, Embase and Cochrane databases was performed to identify randomized clinical trials comparing intra-articular vancomycin use to conventional antibiotic prophylaxis in total hip or knee arthroplasty patients, assessing postoperative infection rates, adverse drug reactions, and venous thrombotic events. Statistical analysis was performed using R (RStudio 2024.04.2), and heterogeneity was assessed with the I2 test.

A total of 1485 patients from five randomized clinical trials were included, with 737 receiving intra-articular vancomycin. The infection rate was 0.54 % in the intervention group and 1.73 % in the control group (RR 0.37; 95 % CI 0.02-8.95; p = 0.369; I2 = 49 %), showing no statistically significant difference between the groups. Adverse reactions to the glycopeptide were reported in six cases (0.8 %) in the intervention group compared to four cases (0.5 %) in the control group (RR 1.50; 95 % CI 1.50-150; p = 0.001; I2 = 0 %). Regarding thrombotic events, there was one case in 647 patients in the intervention group and three cases in 660 patients in the control group (RR 0.45; 95 % CI 0.03-7.02; p = 0.169; I2 = 0 %).

Although no significant difference was found, the intervention group showed a trend toward lower infection rates. Additional RCTs with larger sample sizes are required to confirm these findings.

The prospective registration of the meta-analysis was conducted on PROSPERO in July 2024 with the protocol number 565988.

Bone and joint infections (BJIs) cause significant morbidity, and current guidelines suggest treatment with parenteral antibiotics for 4-6 weeks. However, utility of oral antibiotics as a potential alternative has yet to be thoroughly investigated. To provide a statistical appraisal of literature comparing treatment success and complication rates of oral antibiotics to parenteral antibiotics for BJIs.

PubMed, Embase, Cochrane, and Web of Science databases were queried for studies published by November 12, 2024. Randomized controlled trials (RCTs) comparing parenteral to oral regimens for the entire treatment duration were included, as well as comparative studies evaluating "early switch" therapy, defined as switching from parenteral to oral antibiotics within 28 days. Data was pooled and sub-analyzed according to design (RCTs or early switch cohorts). Treatment successes and complications for parenteral and oral groups were assessed via DerSimonian-Laird binary random-effects modeling with a p-value < 0.05 indicating significance.

Six RCTs (1,310 patients) compared treatment success of parenteral or oral regimens for the duration of the infection treatment, and six retrospective cohort studies (1,106 patients) compared parenteral therapy to early switch therapy. Meta-analysis of RCTs demonstrated no significant difference for treatment success rates for oral versus parenteral antibiotics (OR 1.09 [0.79-1.51], p = 0.93, I2 = 0.00%). Six early switch cohort studies demonstrated that oral antibiotics had significantly higher success (OR = 1.70 [1.13-2.54], p = 0.01, I2 = 0.00%). Meta-data of both RCTs and early switch cohort studies demonstrated no significant difference in complication rates.

No difference in treatment success rates or complication rates was found when comparing oral and parenteral antibiotics. Oral antibiotics are a possible option for treatment of BJIs.

Introduction: Peri-prosthetic joint infection (PJI) is a significant complication of arthroplasty, lacking a single gold standard diagnostic test. Synovial fluid white blood cell (WBC) count and polymorphonuclear neutrophil (PMN) proportion are widely used diagnostic tools, but their optimal cutoffs remain unclear, particularly for chronic PJI. Material and methods: This systematic review and meta-analysis included 74 studies published between 2000 and 2024. Data on diagnostic performance (sensitivity, specificity, and diagnostic odds ratios - DORs) of WBC count and PMN proportions were analysed. Sub-group analyses and heterogeneity assessments were performed, and optimal cutoffs for diagnostic accuracy were identified. Results: The meta-analysis revealed a WBC count summary DOR of 58.38 (95 % CI - confidence interval: 48.48-70.32) with an area under the curve (AUC) of the summarized receiver operating characteristic curve of 0.952. The PMN proportion showed a DOR of 43.17 (95 % CI: 35.31-52.79) and an AUC of 0.941. Optimal diagnostic thresholds for chronic PJI were WBC count > 2600 cells per microlitre and PMN > 70 %. Rule-in thresholds (specificity > 95 %) were WBC count ≥ 3000 cells per microlitre and PMN ≥ 75 %, while rule-out thresholds (sensitivity > 95 %) were WBC count ≤ 1500 cells per microlitre and PMN ≤ 65 %. Confounding conditions such as fractures, inflammatory arthritis, and metal-related reactions reduced test accuracy. Conclusions: Synovial fluid analysis remains a critical diagnostic tool for chronic PJI. Thresholds of WBC count < 1500 and > 3000  cells per microlitre and PMN < 65 % and > 75 % provide reliable negative and positive predictive values. A standardized diagnostic framework is essential for addressing remaining controversies and ensuring consistent interpretation across clinical settings.

In the absence of standard criteria for prosthetic joint infections (PJI), several diagnostic modalities have been proposed mostly concentrating on novel biochemical markers. The physical chemistry markers received scarce attention. Synovial fluid (SF) viscosity could be considered as marker for PJI, however, its diagnostic value of PJI remains unknown. Our study aimed to determine the potential of SF viscosity as a diagnostic marker of PJI and compare it to SF cell count with differential (CCD). We prospectively analysed 123 SF samples (58 septic and 65 aseptic) for viscosity and CCD of SF obtained during hip and knee revision procedures. The diagnosis of PJI based on EBJIS criteria. The viscosity cut-off for PJI was calculated and the diagnostic power was compared to CCD. The mean SF viscosity in the PJI group was 8.5 ± 0.4 mPa s and 103.2 ± 18.8 mPa s in the aseptic group (p < 0.05). SF viscosity achieved 100% sensitivity and 85.3% specificity, with AUC 0.832 (95% CI 0.739, 0.925). Combination of SF viscosity and CCD achieved AUC 0.951 (95% CI 0.919, 0.987). SF viscosity is more sensitive but slightly less specific in diagnosing PJI than SF CCD. Best diagnostic value is achieved combining SF viscosity with CCD in detection of PJI.

The reported success rate of debridement, antibiotics and implant retention (DAIR) for periprosthetic joint infection varies considerably between studies, despite institutions reporting use of the same procedure. In this narrative review, we aim to delineate the differences between the various DAIR approaches and highlight why they influence the outcome.

We performed a PubMed and internet search investigating the different approaches for DAIR and their associated outcomes.

Twenty-two studies with defined infection criteria, consisting of 50 or more PJI cases and a follow-up of one year or longer were included.

Most studies did not report whether the presence of a sinus tract was a criterion for not performing DAIR, and the use of biofilm-active agents for curative DAIR was only reported in a few studies. The duration of infection as criterion for early postoperative and acute hematogenous infection varied between studies. The epidemiology of host factors and microorganisms, healthcare systems, patient-doctor-interactions and decision-making processes for surgical interventions vary worldwide, and so do the indications for DAIR.

Studies should precisely declare the indication for DAIR, the variables that influence decision-making for treatment options, the surgical technique applied and the type and duration of antimicrobial therapy. Such an approach will increase the quality of research data and allow the development of recognized subcategories of DAIR.

Periprosthetic joint infection (PJI) is an uncommon, but serious complication in total joint arthroplasty. Personalized risk prediction and risk factor management may allow better preoperative assessment and improved outcomes. We evaluated different data-driven approaches to develop surgery-specific PJI prediction models using large-scale data from the electronic health records (EHRs).

A large institutional arthroplasty registry was leveraged to collect data from 58,574 procedures of 41,844 patients who underwent at least one primary and/or revision hip and/or knee arthroplasty between 2000 and 2019. The registry dataset was augmented with additional clinical, procedural, and laboratory data from the EHRs for more than 100 potential predictor variables. The main outcome was PJI within the first year after surgery. We implemented both traditional and machine learning methods for model development (lasso regression, relaxed lasso regression, ridge regression, random forest, stepwise regression, extreme gradient boosting, neural network) and used 10-fold cross-validation to calculate measures of model performance in terms of discrimination (c-statistic) and calibration.

All models discriminated similarly in predicting PJI risk, with negligible differences of less than 0.08 between the best- and worst-performing models. The relaxed and fully relaxed lasso models using the Cox model structure outperformed the other models with concordances of 0.787 in primary hip arthroplasty and 0.722 in revision hip arthroplasty, with the number of predictors ranging from nine to 41. The concordances with the relaxed lasso models were 0.681 in primary and 0.699 in revision knee arthroplasty, with a higher number of predictors in the models. Predictors included in the models varied substantially across the four surgical groups.

The incorporation of additional data from the EHRs offers limited improvement in PJI risk stratification. Furthermore, improvement in PJI risk prediction was modest with the machine learning approaches and may not justify the added complexity.

Prosthetic arthroplasties are continuing to increase in the United States. While prosthetic joint infections are a less common adverse event, they can have a devastating impact on the patient as well as have a large economic burden on the health care industry. Prosthetic joint infections can be surgically managed by debridement, antibiotics, and implant retention, 1-stage revisions, 2-stage revisions, resection arthroplasties, arthrodesis, and amputations. Antimicrobial therapy typically includes 4 to 6 weeks of parenteral or highly bioavailable oral agents. Suppressive and chronic oral antimicrobial therapy may be pursued depending on the pathogen, clinical scenario, and retention of the prosthesis.

Debridement with antibiotics and implant retention (DAIR) is commonly utilized for treatment of prosthetic joint infection (PJI) in total knee arthroplasty (TKA), particularly in cases of acute PJI. Reported success rates of DAIR have been highly variable, but the overall success rate of DAIR cohort studies is approximately 70 to 80%. However, no large database studies have investigated the success rate of DAIR. Therefore, we seek to provide a framework for large-database analysis of PJI interventions and their outcomes and to assess the success rate of DAIR. We queried the MarketScan Database for patients who underwent a DAIR (CPT 27310 and/or CPT 27486) procedure for indication of PJI (ICD-10 T84.53 OR T84.54) between January 1, 2017 and December 31, 2021. We identified reoperations (i.e., stage 1 revision, amputation, or arthrodesis) indicating failure of DAIR. Failure of DAIR treatment was defined by subsequent reoperation. We also identified prescriptions of suppression antibiotics more than 6 months after DAIR. We identified 1,018 patients who underwent a DAIR procedure for PJI. Of these patients, 195 (19.2%) underwent reoperation within 1 year and an additional 178 (17.5%) were prescribed suppressive antibiotics. For 780 patients with a minimum of 2 years of follow-up, 164 (21%) underwent reoperation and an additional 179 (22.9%) were prescribed suppressive antibiotics. Patients with obesity and patients younger than 60 years had significantly higher rates of having reoperation or suppressive antibiotics at 1 year following DAIR. DAIR is a viable option in the treatment of PJI, with an approximately 19% rate of reoperation at 2 years. Our findings are consistent with that of previously published literature.

Periprosthetic joint infection (PJI) is a significant and challenging healthcare issues. Accurate diagnosis is essential for effective treatment. The aim of our study is to underscore the usefulness of the new EBJIS definition and criteria when applied in a developing country department.

We conducted a retrospective analysis of a single-center cohort of consecutive revision arthroplasties (January 2018-June 2024). This study was carried out at the Department of Orthopedics and Trauma Surgery in the University Hospital Fattouma Bourguiba in Monastir, Tunisia. Were included in our research patients who underwent revision surgery for arthroplasties due to septic failure. Exclusion criteria were: surgery performed within the previous six weeks, antibiotic-loaded bone cement spacer in place, the second step of a two-stage revision and periprosthetic fractures.

A total of 46 patients were included in the study. According to the EBJIS criteria, our cohort was divided into two groups: "likely infection" including 12 patients (26.1%) and "confirmed infection" with 34 patients (73.9%). Clinical signs like inflammation (Se 85.3%, PPV 76.32%) and pain (Se 76.47%, PPV 70.27%) demonstrate higher sensitivity but low specificity. Among paraclinical tests, a CRP level > 10 mg/dL is highly sensitive (97.06%), while PMN > 80% shows perfect specificity (100%). Tissue samples with more than two positives and cultures with the same microorganism exhibit high sensitivity (96.66% and 80%) and PPV (84.85% and 85.71%).

Establishing PJI diagnosis is challenging and depends on paraclinical testing. We highlight the lack of important diagnostic instruments in settings with limited resources.

Prosthetic joint infection (PJI) is a devastating complication of arthroplasty surgery, mostly caused by Gram-positive pathogens, including Staphylococcus aureus and coagulase-negative staphylococci. Multidrug resistance is of major concern in this setting: (a) it can negatively impact outcome, restricting the use of the most effective antimicrobials; (b) it may influence the choice of surgical strategies; and (c) it restrains the therapeutic options to newly labelled antimicrobials with limited experience in PJI.

To provide a comprehensive overview of the clinical impact of antimicrobial resistance in Gram-positive PJI and on current and innovative therapeutic strategies.

The review is based on PubMed searches for relevant topics, including multiresistant staphylococci PJI and the discussed specific therapeutic approaches. Given the very few randomized trials in this setting, discussion is mostly based on observational studies and the experience and opinion of the authors.

Methicillin resistance is an important concern in staphylococcal PJI, especially in coagulase-negative staphylococci. However, its impact on the outcome is controversial. Conversely, rifampicin and/or fluoroquinolone resistance are associated with worse prognosis and might be considered when defining difficult-to-treat pathogens in the PJI setting. There is very little experience with recently developed anti-Gram-positive antimicrobial in PJI, but evaluations of their antibiofilm activities are promising, and some of them might represent significant advances regarding antimicrobial tolerance (such as tedizolid) or pharmacokinetic profiles (such as dalbavancin) during long-term treatment required for PJI. Evaluation of innovative strategies in this setting is crucial, including repositioning of current surgical options using local antimicrobial delivery, pharmacokinetic monitoring and modelling to optimize antimicrobial therapy, suppressive antimicrobial treatment and/or phage-based approaches.

PJIs caused by resistant Gram-positive bacteria-including rifampicin- and/or fluoroquinolone-resistant staphylococci-may be associated with a poorer prognosis. It is therefore essential to optimize medical and surgical management, and to find new therapeutic alternatives.

Contezolid has activity against methicillin-resistant Staphylococcus aureus (MRSA), a common cause of orthopedic infection. In a rat model of foreign body osteomyelitis, 1.3 log10 cfu/g bone and 0.5 log10 cfu/k-wire reduction in MRSA was found in tibiae (P = 0.0186) and K-wires, respectively, of contezolid-treated compared to untreated rats. No MRSA was recovered from animals receiving rifampin alone or in combination with contezolid or vancomycin. There was no emergence of resistance to contezolid, vancomycin, or rifampin.

Treatment failure remains an issue in periprosthetic joint infection (PJI). Bacteriophages offer new treatment options. However, there is still a lack of evidence to better define their usefulness and administration. We report a case in which antibiotic suppression was successful only after administration of bacteriophages.

Antibiotic suppression was the only option for a 94-year-old male with methicillin-resistant Staphylococcus aureus (MRSA) PJI of the hip and of the knee. As the hip PJI could not be suppressed adequately, bacteriophages were administered locally and systemically together with daptomycin. This combined approach led to sufficient clinical improvement for further oral antibiotic suppression, although without infection eradication.

The administration of bacteriophages may be a valuable, less-invasive adjunct therapy to successfully suppress PJI. Bacteriophage selection, preparation and administration, however, remains associated with administrative obstacles, greatly limiting availability and practicability. Nevertheless, research and developments in this domain should be pursued, particularly considering issues with future antibiotic limitations and cost associated with treatment failure in PJI.

Orthopedic implant-associated infections such as prosthetic joint infections (PJIs) lead to devastating complications for patients and impose significant financial burdens on the healthcare systems. Although the primary orthopedic implant associated infection rate is relatively low (0.3-9%), the reinfection rate after implant revisions can be as high as 20% to 40%. To evaluate novel therapeutic strategies for preventing and treating infections associated with primary and revision implants, it is essential to develop appropriate animal models that closely emulate clinical realities. Here we discuss existing animal models developed for orthopedic implant revision surgeries including small animal models in rats and mice, and larger animal models in rabbits, sheep, and mini-pigs. While larger animal models offer the advantage of more closely mimicking human surgical procedures, implant dimensions, and infection treatment protocols, rodent models are more cost-effective and better suited for screening experimental prophylaxes and therapeutics. Existing animal revision models have focused on primary infections established by Staphylococcal aureus (S. aureus) and revisions involving both one-stage and two-stage procedures. Further development of smaller animal implant revision models that implement more clinically relevant surgical procedures and recapitulate polymicrobial infections could facilitate the discovery and more rigorous evaluation of novel implant coating prophylaxes and therapeutics for reducing reinfection rates following implant revisions.

Research into the optimal antibiotic management of musculoskeletal infections has advanced tremendously over the past quarter century, including over a dozen randomized controlled trials and numerous observational studies. This review examines the rationale for and evidence base supporting modern approaches to antibiotic decision making and stewardship in orthopedic infections. Specific practice advances discussed include the increased and earlier use of oral antibiotics, other principles of antibiotic selection (eg, the notion of "bone penetration" and novel local antimicrobial strategies), individualizing durations of therapy, and increasingly selective approaches to empiric antipseudomonal therapy, suppressive antibiotic therapy, and periprocedural antimicrobial prophylaxis following arthroplasty.

Management of recurrent hip prosthetic joint infection (PJI) is challenging. Hip-resection arthroplasty is a last-choice rescue strategy for complex PJI. The main objective was to assess prospectively the mid-term infectious and functional PJI outcomes of patients managed with hip-resection arthroplasty.

In complex multi-operated PJI, hip-resection arthroplasty may cure the infection without any major impact on hip function, which is often already very limited.

This prospective cohort study conducted in a French Referral Center for bone-and-joint infections included all hip PJIs treated with hip-resection arthroplasty from 2004 to 2019. Patients were followed for at least 2 years, with recording of the following events: reinfection, including relapse or new infection, and PJI-related death. Hip functional status was assessed with the modified Merle d'Aubigné-Postel (mMAP) score. The primary outcome was 2-year event-free survival (EFS). The secondary outcomes were the 4- and 6-year EFS rates and hip functional status at 2 years.

We included 30 patients: median age, 65 years; 39% women. Median [IQR] PJI duration was 15 [4-39] months and patients underwent a median of 5 surgical procedures before resection arthroplasty. The 2-year reinfection free-survival was 89.2% (95% CI: 70.2-96.4). After a median follow-up of 70 [32-103] months, we observed: 1 relapse, 4 new infections, 7 revisions for mechanical reasons and 1 PJI-related death. Median mMAP score 2 years postsurgery was 12, versus 7 before; pain reduction was the main benefit of resection arthroplasty.

Hip-resection arthroplasty achieves sepsis and pain control, and can be a valuable last-line rescue strategy for patients with complex or recurrent hip PJIs.

II; monocentric prospective cohort.

Background/Objectives: The vast amount of research and data on periprosthetic joint infection (PJI) is focussed on infections in hip and knee replacements. This article aims to highlight the special features of PJI in shoulders. Methods: This narrative review is based on the recent and most relevant literature regarding PJI in general, and in shoulders in particular. Results: While the majority of findings for PJI in hips and knees can be transferred to infected shoulder arthroplasties, shoulder PJI represents a unique entity with a different microbial profile and its own diagnostic challenges. Conclusions: As profound evidence for shoulder PJI is lacking, diagnostic and therapeutic algorithms should be transferred from those for PJI in hips and knees. Further research is necessary to determine optimal management of shoulder PJI.

Background and aim: Complex bone and joint infections (BJIs), including prosthetic joint infections (PJIs) and infections associated with osteosynthetic materials, present significant treatment challenges that often require surgical intervention and prolonged antibiotic therapy. In France, the incidence of PJIs in knee and hip arthroplasties ranges from 0.79 % to 2.4 %, with staphylococci being the primary pathogens involved. Recent studies have suggested that oral antibiotic therapy may be as effective as intravenous therapy and that 12 weeks of antibiotic treatment are needed. Tetracyclines, particularly doxycycline and minocycline, are of interest because of their broad-spectrum activities, good oral bioavailability, and potential efficacy in treating BJIs. We aimed to provide a literature review on the role of oral tetracyclines in the management of BJIs. Method: We performed a systematic review of the literature identified via an electronic search of PubMed and ScienceDirect. Results: A total of 648 articles were screened, and 31 studies were included. Pharmacological studies demonstrated that the bone to blood penetration ratio ranged from 0.06 to 0.75. Less than 20 % of strains implicated in BJIs exhibited resistance to oral tetracyclines. Four studies demonstrated potential inhibition of strain growth. Eight studies that included 62 patients reported curative treatment, with a success rate ranging from 82 % to 100 % for PJIs regardless of the surgical management. For suppressive therapy, 10 studies that included 201 patients reported success rates ranging from 57 % to 100 %. The rate of adverse effects ranged from 0 % to 14 % for curative treatment and from 0 % to 57 % for suppressive treatment, leading to treatment discontinuation in less than 20 % of cases. Conclusion: This review highlights that the number of studies supporting the use of oral tetracyclines for the treatment of BJIs is limited. More robust pharmacological and clinical studies are needed to confirm the safety and efficacy profiles of oral tetracyclines for the treatment of BJIs.

Background: Microbial analysis of tissue samples represents an important diagnostic tool in the course of revision total joint arthroplasty. Currently, unexpected positive intraoperative cultures are commonly observed during presumed aseptic revision surgery and evoke a degree of uncertainty among physicians. To date, it is unclear if there are deviations in pathogen detection between certified laboratories. Methods: Tissue samples of sixty consecutive patients undergoing presumably aseptic total hip and knee revision surgery were sent to two different internationally certified accredited laboratories and tested for any microbial growth as well as pathogen differentiation. Results: Each laboratory analyzed 300 samples. Laboratory 1 observed an unexpected positive culture rate of 16.7%; laboratory 2 indicated that 18.3% of all processed specimens showed pathogen growth. In comparison, a consistent microbial evaluation was only present in one patient. The kappa correlation coefficient showed a poor correlation between the two laboratories in all evaluated categories. Coagulase-negative staphylococci represented the most common pathogens of laboratory 1, while laboratory 2 predominantly observed cutibacterium acnes species. Within a mean follow-up period of 17.6 ± 18.6 months (range: 0-63 months), there was no revision due to periprosthetic joint infection. Conclusions: Unexpected positive culture results during presumed aseptic revision surgery remain a significant clinical challenge. This study is the first of its kind to evaluate the convergence of laboratory findings in the context of aseptic revision surgery. Our results suggest that even established and certified laboratories show substantial discrepancies. Thus, a careful interpretation of unexpected bacterial cultures after revision surgery is mandatory. Given the uncertainty inherent in laboratory findings, a precise clinical and histopathological evaluation of this patient cohort should be ensured.

A hub and spoke model for optimizing long-term treatment of chronic staphylococcal infections with dalbavancin based on therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) was implemented. This multicentric retrospective cohort study included patients receiving dalbavancin monotherapy lasting >6 weeks at different spoke hospitals having treatment optimized by means of a TDM-guided ECPA program at a hub hospital. Optimal pharmacokinetic/pharmacodynamic target against staphylococci with an MIC up to 0.125 mg/L was defined as dalbavancin concentrations >8.04 mg/L. Patients received dalbavancin therapy for curative (curative group) or suppressive (suppressive group) purposes. Clinical outcome was assessed by means of repeated ambulatory visits. A total of 12 spoke hospitals applied for 414 TDM-based ECPA for 101 patients, of whom 64.4% (65/101) were treated for curative and 35.6% (36/101) were for suppressive purposes. In the curative and suppressive groups, TDM-based ECPA optimized treatment for up to 14 and 28 months, respectively, and ensured median optimal exposure of 95.7% and 100%, respectively. In the curative group, having <70% of treatment time with concentrations above the optimal target increased failure risk [odds ratio (OR), 6.71; confidence interval (CI), 0.97-43.3; P = 0.05]. In the suppressive group, infective endocarditis was associated with an increased risk of ineffective treatment (OR, 8.65; CI, 1.29-57.62; P = 0.046). Mild adverse events were reported in 4.5% (5/101) of cases. A hub and spoke TDM-guided ECPA program of dalbavancin may be cost-effective for optimizing long-term treatment of chronic staphylococcal infections and for patients admitted to hospitals lacking in-house MD clinical pharmacologists.

Broad-range polymerase chain reaction (BR-PCR) identifies molecular signatures of microorganisms directly from clinical specimens without requiring microbial growth in culture. BR-PCR may be a powerful tool to reveal microbial causes of infectious diseases, but the impact on diagnosis and clinical management has yet to be fully defined. Consequently, the aims here were to investigate how bacterial, fungal, and mycobacterial (AFB) BR-PCR perform compared to microbiology culture methods in detecting microorganisms and to assess clinical utility, defined as the ability of the results to change antimicrobial therapy or treatment duration. Between 2018 and 2021, 348 unique specimens were sent from 327 patients seen within the University of Maryland Medical System (UMMS). Patient charts were reviewed retrospectively. Organisms identified by BR-PCR were compared to bacterial (n = 302), fungal (n = 137), and AFB (n = 111) cultures to determine concordance and were evaluated to determine if they led to a change in clinical management. Agreement in organism(s) reported by BR-PCR and culture was considered concordant for calculating performance data. Sensitivity of BR-PCR compared to concordant culture results was 30.9% for bacteria (25/81; 95% CI: 21.8-41.6%), 18.8% for fungi (3/16; 95% CI: 5.8-43.8%), and 33.3% for AFB (1/3; 95% CI: 5.6-79.8%) detection. The bacterial negative percent agreement of 80.1% (165/206) may reflect antibiotic pretreatment or detection of fastidious organisms. Despite longer turnaround times, BR-PCR results changed clinical care in 6% of cases. Based on these findings herein, the clinical use of BR-PCR would be best utilized when fastidious organisms are suspected, or specimens remain culture negative, but should not replace routine culture methods at this time.IMPORTANCEDetermining infectious etiology can be challenging in patients with chronic presentation and in those receiving empiric therapy. In addition to the standard of care (microbiology cultures), providers can order a broad-range polymerase chain reaction and sequencing (BR-PCR) test to identify microorganisms directly from clinical specimens and independently from culture. While studies have been done from individual hospitals or systems, there is a lack of broadly applicable clinical evidence detailing clinical scenarios in which BR-PCR should be utilized. This study adds to the growing body of literature surrounding BR-PCR clinical usage, examining assay performance and clinical utility of BR-PCR test results. Although BR-PCR and culture had low concordance among organisms identified, it was shown to complement the standard of care for uncommonly isolated and fastidious organisms. Overall, BR-PCR results changed clinical management in 6% of cases, which is similar to other studies that include a broad representation of specimen types.

Chronic osteomyelitis caused by implant infections is a common complication following orthopedic surgery. Preventing bacterial infection and simultaneously improving bone regeneration are the key for osteomyelitis. Current treatments include systemic antibiotics and multiple surgical interventions, but the strategies available for treatment are limited. In this study, a multifunctional engineered Bacillus subtilis (B. sub) hydrogel with sulfasalazine (SSZ) is developed to treat methicillin-resistant Staphylococcus aureus (MRSA) infection and anti-inflammatory and promote bone regeneration. B. sub in alginate hydrogels protects B. sub from being cleared by the host immune system while allowing the release of its bioactive substances, including antibacterial peptides and anti-inflammatory agents such as SSZ. The results show that the engineered probiotic hydrogels exhibit excellent antibacterial efficacy against MRSA (97 %) and prevent the development of bacterial resistance. The antibacterial effect is primarily mediated through the secretion of bioactive peptides by B. sub, which not only inhibit MRSA growth but also reduce the likelihood of resistance development. Meanwhile, the probiotic hydrogel has a greater ability to induce M2 polarization of macrophages and promote angiogenesis, resulting in enhanced osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) and thus enhancing bone regeneration. This engineered probiotic hydrogel offers a promising strategy by simultaneously combating bacterial infection and enhancing osteogenic differentiation for chronic osteomyelitis.

Cocktails containing glucocorticoids for local infiltration analgesia (LIA) are highly advocated and effective in managing pain in total joint arthroplasty (TJA). However, it remains ambiguous whether this protocol maintains its safety and efficacy in the treatment of periprosthetic joint infection (PJI), a devastating complication of TJA.

A retrospective study was conducted on 299 single-stage revision cases for PJI spanning the years 2010 to 2021. Of these, 127 received LIAs containing high-dose compound betamethasone (CB) were termed the CB group, and the other 172 were termed the non-CB group. The rates of re-infection and other postoperative complications, along with postoperative visual analog scale (VAS) scores, and opioid consumption were compared.

During minimum 2-year follow-up, there was no significant difference in the re-infection rate between the non-CB and CB groups (9.3 versus 8.7%; P = 0.85), consistent within the subsets of hip (8.4 versus 4.5%; P = 0.51) and knee (10.4 versus 13.3%; P = 0.60) PJIs individually. The administration of high-dose CB was neither an independent risk factor for reinfection (P > 0.05; 95% CI [confidence interval] including 1) nor was it associated with the occurrence of reinfection (P > 0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the CB group (P < 0.05). In the first 48-hour postoperative period, the CB group exhibited lower mean scores in both resting and movement VAS evaluations (P < 0.05). For knees, the movement VAS scores of the CB group remained lower even at 72 hours post-surgery (P < 0.001). Furthermore, within the first 72 hours post-surgery, the CB group required less additional opioid analgesics than the non-CB group (P < 0.05).

A LIA with a high-dose CB reduces postoperative pain, opioid consumption, and the incidence of PONV following a single-stage revision without affecting reinfection and other complication rates.

Corynebacterium spp. is a rare culprit in periprosthetic joint infections (PJIs), with limited data available on outcomes and appropriate treatment course. The aim of this study was to evaluate the success rate of a clinical cohort of patients with PJI, where Corynebacterium spp. was the causative organism (CPJI), treated according to an institutional algorithm based upon European Bone and Joint Infection Society guidelines.

From the institutional bone infection registry, 44 patients treated for CPJI between 2007 and 2023 were identified. CPJIs were divided into 2 groups according to the isolated microbes: monomicrobial (14 [32%]) and polymicrobial (30 [68%]). Patients were treated with debridement, antibiotics, and implant retention (DAIR; 14 [32%]) or with 1- or 2-stage implant exchange (reimplantation group; 30 [68%]). In 13 (30%) cases, antibiotic combination with rifampicin was used.

Out of 44 patients, 4 required further treatment. In monomicrobial CPJI, the treatment course was successful in all patients, whereas in polymicrobial CPJI it was successful in 87%. Antibiotic combination including rifampicin was used in 4 monomicrobial cases (29%) and 9 polymicrobial (30%) cases. In the polymicrobial group, DAIR was successful in 90% (9/10), while the reimplantation group had an 85% (17/20) success rate.

In contrast with the previously published papers on CPJI, the results in our cohort were good, with the total cure rate being 91%. The cure rate was slightly lower in the polymicrobial group compared with the monomicrobial: 87% and 100%, respectively. Surgical therapy according to the established institutional algorithm resulted in a high success rate.

Opioid use in the United States has increased dramatically. Bacterial infections are common among persons who inject drugs (PWID), and there is a disparity in the care these individuals receive. As such, outcomes associated with these infections can be poor. Healthcare providers can address these disparities through optimal pharmacotherapy recommendations and assistance with changing approaches to the management of PWID.

Periprosthetic joint infection (PJI) represents one of the most devastating complications following total joint arthroplasty, often necessitating additional surgeries and antimicrobial therapy, and potentially leading to disability. This significantly increases the burden on both patients and the healthcare system. Given the considerable suffering caused by PJI, its prevention and treatment have long been focal points of concern. However, challenges remain in accurately assessing individual risk, preventing the infection, improving diagnostic methods, and enhancing treatment outcomes. The development and application of artificial intelligence (AI) technologies have introduced new, more efficient possibilities for the management of many diseases. In this article, we review the applications of AI in the prevention, diagnosis, and treatment of PJI, and explore how AI methodologies might achieve individualized risk prediction, improve diagnostic algorithms through biomarkers and pathology, and enhance the efficacy of antimicrobial and surgical treatments. We hope that through multimodal AI applications, intelligent management of PJI can be realized in the future.

The emergence of antibiotic resistance, biofilm formation, and internalization by host cells contribute to a high risk of chronic infections, highlighting the necessity to develop novel therapeutic strategies. Identification of natural host defense peptides (HDPs) with promising antimicrobial and antibiofilm activities led to the development of synthetic peptides with broad-spectrum efficacy. However, few studies have examined their effect on anaerobic bacterial species. This study aimed to test the effect of synthetic HDPs on Cutibacterium acnes, an anaerobe species involved in 10% of prosthesis joint infections (PJI). A preliminary screen identified three peptides (DJK5, AB009-D, and AB101-D) with promising activity against four C. acnes strains (two of which were isolated from PJI). A bactericidal effect was observed for the three peptides with 50% of planktonic bacteria killing for AB009-D and AB101-D after only 3 hours of contact. DJK5 and AB009-D inhibited the C. acnes adhesion on plastic and titanium supports with a 2-log decrease in bacterial cells. In the presence of peptides, the morphology of C. acnes cells was altered with an increase in cell length observed, especially for one of the non-PJI-related strains. Against mature biofilms, AB101-D was the most effective with an approximate 2-log decrease in adhered CFUs, indicating the induction of bacterial dispersion or death. DJK5 also inhibited C. acnes internalization by osteoblasts, with a reduction of the internalized bacteria quantity for three strains. Overall, this study demonstrates that synthetic HDPs are effective against anaerobic bacteria and hold promise as novel therapeutic candidates to prevent or treat C. acnes PJIs.IMPORTANCEThe emergence of antibiotic tolerance highlights the necessity to develop novel therapeutic strategies with promising antimicrobial but also antibiofilm activities. In this study, we tested the effect of synthetic host defense peptides (HDPs) on Cutibacterium acnes, an anaerobic species, rarely studied, whereas involved in 10% of prosthesis joint infections (PJI). In our study, we demonstrate that the selected synthetic HDPs are effective against this anaerobic bacteria, both as a preventive treatment (effect on planktonic growth, bacterial adhesion, and biofilm formation) and against internalization of C. acnes by osteoblasts, revealing that these peptides are promising as novel therapeutic candidates to prevent or treat C. acnes PJIs.

Introduction: In periprosthetic joint infection (PJI), there is a paucity of prospective data comparing debridement, antibiotics and implant retention (DAIR) with two-stage revision while also accounting for time since the initial arthroplasty. Additionally, comparisons often lack patient-centred measures. A desirability of outcome ranking for PJI (DOOR-PJI) unifies joint function, infection cure and mortality into one outcome. We aimed to describe the DOOR-PJI distribution in a large patient cohort and use it to compare DAIR and two-stage revision. Methods: Adults with a newly diagnosed hip or knee PJI from the prospective Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study were analysed. Patients from 27 hospitals were included. PJI was classified as "early" or "late". The primary outcome was the novel DOOR-PJI at the 2-year follow-up. Results were expressed using win ratio (WR) values. A WR > 1.0 indicates that two-stage revision was superior to DAIR. Results: A DOOR was available for 533 patients. The most common treatments were DAIR (297 patients, 56 %) and two-stage revision (139 patients, 26 %). In early PJI, DAIR was superior to two-stage revision (WR 0.51, 95 % confidence interval (CI) [0.30-0.86], p = 0.012). In late PJI, two-stage revision was superior to DAIR (WR 1.61, 95 % CI [1.11-2.33], p = 0.012). These findings persisted following stratification by comorbidities, affected joint, symptom duration and a sensitivity analysis applying the initial (rather than the main) surgical strategy at day 90. Conclusions: In the first application of a DOOR in orthopaedics, DAIR was superior to two-stage revision for early PJI. Conversely, two-stage revision was superior compared with DAIR for late PJI. These findings were independent of comorbidities and symptom duration.

The ideal substitute for in situ reconstruction of aortic graft or native aortic infection has yet to be defined. Though recognized as resistant to infection, cryopreserved arterial allograft (Allograft) presents problems of availability when treating emergent cases, with the risk of long-term aneurysmal degeneration. Commercially available bovine pericardial substitutes (Pericard) seems to be an alternative, with promising results in the recent literature. The goal of this study was to compare the results of these two substitutes.

Between January 2010 and December 2023, we conducted a retrospective observational study in two tertiary centers, including all patients having undergone in situ surgery for aortic graft or native aortic infections with reconstruction by Allograft or Pericard. Survival, reinterventions and reinfections were analyzed according to the Kaplan-Meier method and Cox regression model.

All in all, 169 patients were included in the study with 103 aortic graft infections (60.9%), 33 aortic endograft infections (19.5%), and 33 native aortic infections (19.5%). Allograft was used in 111 patients (65.7%) and Pericard in 58 (34.3%). The two groups were comparable as regards preoperative risk factors, types of index surgery, and infectious agents, with 41 patients (24.8%) with an aortoenteric fistula. There was no significant difference in postoperative complications. The median follow-up was 18 months (interquartile range, 4-44 months). At 24 months, survival was comparable, with 68 ± 4% for Allograft and 68 ± 6 for Pericard, as was reinfection-free survival with 80 ± 4% for Allograft vs 83 ± 6% for Pericard (P = .722). Reintervention-free survival at 2 years was likewise comparable: 86 ± 4% for Allograft vs 77 ± 8% for Pericard (P = .419).

A pericardial substitute offers the possibility of in situ aortic reconstruction without the problems of availability and with midterm results comparable with those achieved with aortic allografts. Further studies with long-term follow-up are needed to validate the absence of late reinfection and to confirm pericardial substitute patency.

With the rapidly increasing volume of total joint arthroplasty procedures, the incidence of periprosthetic joint infection (PJI) and its associated economic burden are expected to rise. Two-stage reimplantation, a common strategy for PJI management, is costly, as it requires multiple surgeries and hospitalizations, with total costs ranging from $35,000 to $42,000. Given the long hospital stays required for these patients, a quality improvement project was undertaken at the authors' institution to reduce cost of admission (COA) and length of stay (LOS).

We conducted a retrospective review of patients treated for PJI of the shoulder at a single hospital within a large health system. Patients were included if they had a biopsy-proven shoulder PJI treated with 1 of 2 protocols: a conventional, inpatient focused approach or a new, outpatient focused approach. Conventional management involved prosthesis explantation with intraoperative cultures, antibiotic spacer placement, inpatient infectious disease consultation, and inpatient peripherally inserted central catheter placement. The new protocol consisted of outpatient infectious disease clinic referral and peripherally inserted central catheter placement prior to explantation and spacer placement. COA and LOS were compared between the 2 groups.

Sixteen patients were included, 8 in each group. Patients managed with the outpatient-focused protocol had a significantly reduced COA ($17,711 ± 4078) compared to the conventional protocol ($24,233 ± 4967) with a mean difference of $6521, representing a 26.9% cost reduction per patient (P = .006). LOS was significantly reduced in the outpatient-focused group (median: 1.35 days; interquartile range: 1.21-1.89) compared to the conventional protocol group (median: 2.52 days; interquartile range: 1.81-3.21) (U = 10.50; Z = -2.26; P = .024).

The pilot quality improvement initiative resulted in a 27% reduction in COA and a significantly reduced LOS for patients with shoulder PJI. This has broad implications across orthopedics for the management of periprosthetic joint replacement and potential for tremendous impact of reducing healthcare costs.

This study aimed to establish the optimal cutoff value for synovial absolute polymorphonuclear neutrophil (APMN) count in distinguishing between septic and aseptic hip and knee revision arthroplasties. We also investigated its effectiveness as an indicator in revision arthroplasties with challenging microbiological findings, including (i) aseptic cases with a single unexpected positive intraoperative culture (UPICs), (ii) septic cases with unexpected negative ICs (UNICs) and (iii) infections caused by high- and low-virulent pathogens.

A total of 616 revision arthroplasties (177:hip, 439:knee) included. Using European Bone and Joint Infection Society (EBJIS) criteria, 325 (52.8%) were classified as infection confirmed, 271 (44%) infection unlikely and 20 (3.2%) as infection likely. International Consensus Meeting (ICM) 2018 criteria classified 308 (50%) as infected, 269 (43.7%) not infected, and 39 (6.3%) as inconclusive. Diagnostic accuracy was assessed through receiver operating characteristic curves and area under the curve (AUC).

Optimal APMN count thresholds using EBJIS criteria in hip and knee joints were 783.6 cells/µL (AUC: 0.92) and 549 cells/µL (AUC: 0.91), respectively. With the ICM criteria, its optimal cutoff values remained unchanged, except for the knee, which shifted to 594.2 cells/µL. Comparing UPICs to other aseptic cases showed no significant median APMN count differences when both criteria's applied, potentially ruling out infection suspicion. In septic cases, APMN counts differed between UNICs and culture positives but were statistically significant with EBJIS criteria (Hip:p = 0.01, Knee:p = 0.03) but not with ICM (p = 0.08). Median APMN counts were significantly elevated in high-virulent compared to low-virulent organisms, with similar trends in most of the other markers. Compared to alpha-defensin, APMN count exhibited better AUC, sensitivity and negative predictive value.

The APMN count represents a simple and inexpensive method that may serve as a complementary diagnostic marker in hip and knee revision arthroplasties with challenging microbiological findings.

Level III, retrospective study.

The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and offer future directions for research to optimize patient outcomes.

Of 313 patients whose outpatient parenteral antimicrobial therapy was managed by an ID physician, only 39 [12.5%, 95% CI (8.8%-16.1%)] had clinical decisions influenced by erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both. ESR/CRP ordering was associated with $530 in excess cost per treatment course (average duration 5.1 weeks) representing a diagnostic stewardship opportunity.

Assess the feasibility of utilizing the ratio of blood inflammation to coagulation markers as a potential periprosthetic joint infection (PJI) diagnostic tool.

A retrospective analysis was conducted, involving 133 PJI and 93 aseptic loosening patients. Levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count, mean platelet volume, fibrinogen, D-dimer, and ratios of CRP to fibrinogen, ESR to fibrinogen, platelet count and mean platelet volume ratio (PC/MPV), and D-dimer were compared. Receiver operating characteristic curves and Youden's index were employed to assess the diagnostic efficacy of these biomarkers.

PJI patients had significantly higher levels of CRP, ESR, PC/MPV ratio, fibrinogen, D-dimer, CRP/(PC/MPV) ratio (CPR), CRP/D-dimer, CRP/fibrinogen (CFR), ESR/(PC/MPV) ratio, ESR/D-dimer, and ESR/fibrinogen. Area under the curve (AUC) values for fibrinogen, CRP, and ESR in diagnosing PJI were comparable. AUC values for CPR and CFR were akin to those of ESR. AUC values for combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen in diagnosing PJI were akin to that of combined CRP and ESR.

Fibrinogen, CPR, CFR, combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen could be considered as new adjunct markers for diagnosing PJI.

The diagnostic accuracy of 16S rDNA PCR, multiplex PCR (mPCR), and metagenomic next-generation sequencing (mNGS) in periprosthetic joint infections (PJIs) remains unclear.

This study aims to evaluate the diagnostic accuracy of 16S rDNA PCR, mPCR, and mNGS in PJI.

Data sources: Data sources included PubMed and Embase (January 1, 2000-March 1, 2024), with no language restrictions.

Studies containing sufficient data to construct a 2 × 2 contingency table allowing for sensitivity and specificity calculation were considered.

Participants included adults (≥18 years) with PJI and appropriate control groups.

Tests included 16S rDNA PCR, mPCR, and mNGS.

Diagnosis required adherence to Musculoskeletal Infection Society, Infectious Diseases Society of America, International Consensus Meeting, European Bone and Joint Infection Society criteria. Studies employing alternative author-defined criteria were included only if they did not rely solely on positive cultures to define PJI.

Quality Assessment of Diagnostic Accuracy Studies 2 was used.

A bivariate model calculated pooled diagnostic odds ratios (DORs), sensitivities, and specificities, each with 95% CIs.

Seventy-nine studies were included, comprising 3940 PJI cases and 4700 uninfected controls. Pooled sensitivity/specificity were 80.0% (95% CI, 75.4-84.3%)/94.0% (95% CI, 91-96%) for 16S rDNA PCR; 62.2% (52.5-70.9%)/96.2% (93.2-97.9%) for mPCR; and 88.6% (83.3-92.4%)/93.2% (89.5-95.6%) for mNGS. Notably, mNGS had the highest DOR (105.9; 95% CI, 60-186.9). A sensitivity analysis excluding lower-quality studies resulted in increased DORs for all methods.

These molecular techniques display strong diagnostic accuracy for identifying PJI. Although mNGS yielded the highest DOR, numerous technical and practical challenges preclude its routine use for PJI diagnosis. Significant heterogeneity across studies warrants cautious interpretation and underscores the need for future comparative research.

Introduction: Endoprosthetic replacement (EPR) is the preferred limb salvage method for musculoskeletal tumours involving bone; however, infection rates range from 8 % to 12 %. We investigated the impact of antibiotic prophylaxis at primary implantation on the development of prosthetic joint infection (PJI). Methods: We conducted a retrospective analysis of patients who underwent primary EPRs between 2010 and 2021. Prosthetic joint infections were identified and classified according to criteria from the European Bone and Joint Infection Society (EBJIS). The follow-up period extended until an infection was identified, subsequent surgery for non-infectious reasons occurred or the last known follow-up was conducted. For all primary procedures, we collected details of postoperative complications at the surgical site, including superficial wound infections, delayed wound healing and wound dehiscence. PJIs were divided into two groups. The first group included patients with an uncomplicated postoperative course, while the second comprised those with either postoperative wound problems or infections from an identifiable source. Results: Out of 1064 patients, 73 (6.9 %) developed PJI within a median follow-up of 25.6 months (IQR 8.8-52.7). A total of 26 % of PJIs were attributed to primary implantation, while 74 % of PJIs were due to secondary causes, with 47 % having wound complications and 27 % presenting acutely. The microbiological profiles between groups differed significantly, with infections from skin flora related to primary implantation and a high proportion of other bacteria (Gram-negatives and enterococci) linked to secondary infections. Conclusions: Skin flora are likely responsible for infections related to the primary procedure, and antibiotic prophylaxis should be optimised accordingly. Additional measures are needed to prevent secondary infections.

Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI.

This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up.

A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777).

Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.

Introduction: The prosthetic knee infection (PKI) rate in most centers ranges from 0.5 to 2% for knee replacements, depending on risk factors. Current PKI definitions may miss the identification of both early and late complications. There is no consensus on preventive or early empiric antibiotic therapy (EEAT) in the one-step exchange strategy for low-risk patients pending microbiology results. The aim of the study was to evaluate the potential role of EEAT in patients with comorbidities in preventing PKI and to evaluate differences in septic failure at 3, 6 and 9 months after prosthetic revision between patients undergoing EEAT and patients not undergoing EEAT. Methods: All adult patients undergoing one-step knee revision surgery at IRCCS Sacro-Cuore Don Calabria Negrar, from January 2018 to February 2021, were retrospectively included in a cohort observational study. Patients on antibiotic therapy before surgery or with preoperative ascertained PKI were excluded. Demographic characteristics, Charlson score, comorbidities, inflammatory markers, microbiological tests, imaging, infectious disease risk score and EEAT data were collected. Any postoperative complication or modification of antibiotic therapy at 14, 30, 90, 180 and 270 days after surgery was collected. Results: A total of 227 patients were included: 114 comorbid low-risk patients received EEAT after surgery, pending microbiological results; while 113 non-comorbid low-risk patients did not receive any antibiotic therapy in the postoperative period. Among the EEAT group, 16 were diagnosed with PKI, compared with 10 in the untreated group. Regarding septic failure during the 9-month follow-up after revision surgery, we registered nine cases in the EEAT arm and four in the untreated arm. In three out of nine cases treated with EEAT who had a post-revision septic failure, the causative microorganism was not successfully empirically targeted by EEAT; in the untreated group, two out of four cases had a post-revision septic failure, despite the targeted treatment of intraoperatively identified causative microorganisms. Conclusions: According to our results, EEAT after revision surgery in patients with comorbidities, who are at higher risk of infection, did not prevent prosthetic knee infections. There was also no evidence of a reduction in subsequent septic failure within nine months of revision surgery between groups. More accurate risk-defining scores are needed to identify patients at risk of PKI complications.