We report a rare case of LVAD infection caused by Coxiella burnetii in a 43-year-old male. The infection was diagnosed after CT-guided abscess sampling, FISHseq analysis, and serology. Conservative therapy with doxycycline and hydroxychloroquine proved unsuccessful. After LVAD removal and heart transplantation, the patient has remained infection-free for three years under antibiotic suppression.

In the original publication [...].

Fracture-related infections (FRI) remains a significant challenge in orthopedic trauma care. Conventional culturing of deep intraoperative samples is the current diagnostic standard, but confirmation occurs postoperatively, delaying targeted treatment. A scoping review was conducted to evaluate the current evidence on intraoperative diagnostics for FRIs. Real-time intraoperative diagnostic techniques may offer earlier detection and improved surgical decision-making, but their clinical value remains uncertain and requires further investigation. Method: A scoping review was conducted using PubMed, Embase, Scopus, and Web of Science. A predefined search strategy incorporating fracture, infections, intraoperative methods, and diagnosis identified 4,075 results. After deduplication, 2,425 abstracts were screened. Twelve studies were initially selected, and following full-text screening and snowballing, ten articles were included, focusing on intraoperative diagnostic modalities for FRIs, particularly fluorescence imaging and frozen section analysis. Results: Frozen section analysis was investigated in three studies, demonstrating high sensitivity and specificity for detecting FRIs, particularly in cases of fracture non-union. One study highlighted its strong negative predictive value, allowing reliable exclusion of active infections during revision surgery, while another confirmed its utility in predicting the absence of infection during conversion to arthroplasty after acetabular fracture fixation. However, its accuracy in diagnosing indolent infections remains uncertain. Fluorescence imaging was examined in three clinical studies, showing promise for real-time visualization of necrotic bone and bacterial presence. Intraoperative fluorescence-assisted imaging proved useful for distinguishing viable from necrotic bone in chronic infections, potentially enhancing surgical precision. Additionally, molecular imaging and fluorescence-guided debridement improved tissue viability assessment and infection detection. A study combining preoperative PET with intraoperative fluorescence imaging demonstrated noninvasive bacterial visualization on osteosynthesis devices. Four additional basic science studies explored fluorescence imaging techniques, providing insights into bone perfusion assessment and molecular tracer applications for bacterial detection. These studies introduced fluorescence-guided models for quantifying periosteal and endosteal blood flow, emphasizing the importance of patient-specific arterial input correction for accurate intraoperative imaging. Conclusions: Intraoperative diagnostic modalities for FRI, including fluorescence imaging and frozen section analysis, show promise in improving real-time infection detection and guiding surgical decision-making. However, current data remains scarce and lacks robust clinical validation. Further high-quality research is necessary to assess the accuracy, feasibility, and clinical impact of these approaches.

Background: Long-term suppressive antibiotic therapy (SAT) is a management strategy for periprosthetic joint infection (PJI) when eradication is unattainable. However, SAT is often associated with adverse events (AEs) that may impact quality of life. This study aimed to evaluate the prevalence and types of AEs, assess patient-reported tolerability, and identify patient- and antibiotic-related factors associated with AEs during SAT for PJI. Methods: A retrospective analysis of a prospectively established cohort of 30 patients receiving SAT for PJI following DAIR (Debridement, Antibiotics, and Implant Retention) or prosthesis exchange between 2019 and 2022 was conducted at a specialized septic surgery department. SAT was indicated for suboptimal surgery or absence of biofilm-active antibiotics and was administered for ≥ 6  months. Structured patient interviews and institutional records were used to capture AEs, treatment modifications, SAT discontinuation, infection-related complications, and subjective tolerability. Patients were stratified by sex, age, BMI, and antibiotic agent. Results: The median SAT duration was 55 weeks (interquartile range (IQR): 40-101). Non-serious AEs occurred in 97 % of patients ( n = 29 ), predominantly affecting the gastrointestinal tract ( n = 63 ), skin ( n = 35 ), and nervous system ( n = 25 ). Treatment modifications were required in 23 % of patients, most frequently with amoxicillin or cotrimoxazole. SAT discontinuation occurred in one patient (3 %) due to multiple AEs. Four patients (13 %) experienced SAEs related to persistent or recurrent infection rather than antibiotic toxicity. Median subjective tolerability was 8 out of 10 (IQR 6-8); 57 % of patients rated tolerability as "good", 37 % as "moderate", and 6 % as "poor". Conclusion: SAT for PJI is associated with a high prevalence of mild to moderate AEs, but treatment discontinuation is rare. Most patients report acceptable tolerability, and serious antibiotic-related complications are uncommon. Careful patient selection, individualized monitoring, and management of AEs are essential to optimize long-term outcomes.

BACKGROUND:Surgical site infections (SSI) are among the most frequently observed healthcare associated infections and represent a significant target to reduce the impact of antimicrobial resistance. Use of a surgical care bundle has demonstrated efficacy in reduction in SSI, but there is a lack of consensus on which elements should be included within such a bundle. The aim of this international consensus was to determine what factors should be utilized to produce an optimal, evidence-led bundle of care that can be utilized in a multidisciplinary manner across specialties and across countries. METHODS:The process employed a modified Delphi methodology. Based on published high-level evidence an international multidisciplinary steering group developed 38 statements for testing with a wider responder panel of healthcare professionals in Europe. The threshold for consensus agreement was set at 75%. RESULTS:A total of 820 responses were analyzed, with the majority of participants being surgeons (59%) and nurses (19.1%) from across Europe. The consensus process evaluated 36 finalized statements covering preoperative, intraoperative, and postoperative SSI prevention practices. Overall, 33 out of 36 statements (92%) reached the predefined consensus threshold of 75% agreement. A high agreement was observed across multiple roles and specialties, although some variation existed for specific topics such as antiseptic irrigation, use of antimicrobial sutures, and plastic adhesive drapes. CONCLUSION:This large consensus of European HCPs involved in the surgical care of patients achieved strong levels of consensus across most of the proposed statements on elements of an SSI prevention bundle. These practice recommendations could be adopted as an evidence- and expert-based care bundle for the prevention of SSI. The project was registered at www.researchregistry.com.

Aims The diagnosis of periprosthetic joint infection (PJI) remains a challenge, as no single diagnostic test shows high diagnostic accuracy. Recently, the measurement of synovial biomarkers has shown promising results. The aim of this study was to present a novel multiplex micro-enzyme-linked immunosorbent assay (ELISA) method for the rapid and simultaneous measurement of alpha-defensin, interleukin (IL)-6, and calprotectin developed in a model buffer system and human spiked synovial fluid. Methods A microfluidics- and chemiluminescence-based multiplex micro-ELISA point-of-care testing system was employed for the rapid and simultaneous measurement of alpha-defensin, calprotectin, and IL-6 developed in a model buffer system and spiked human synovial fluid. Cut-off values of 1.56 mu g/ml for alpha-defensin, 50 mu g/ml for calprotectin, and 0.031 mu g/ml for IL-6 were extracted from the literature as optimal cut-off values for the diagnosis of PJI, and were used for comparison. Results Limit of detection (LoD) was determined for each individual biomarker by means of calibration curves with serial dilutions in a model buffer system. LoDs of 0.008, 0.002, and 0.00014 mu g/ml were determined for alpha-defensin, calprotectin, and IL-6, respectively. The spiked synovial fluid assay determined LoDs of 0.08, 0.31, and 0.004 mu g/ml for alpha-defensin, calprotectin, and IL-6, respectively. Conclusion These findings highlight the proposed platform's unique features, including simultaneous measurement of three key synovial biomarkers, minimal sample volume requirements (5 to 50 mu l), lower LoDs compared to conventional tests, and a short processing turnaround time of 22 minutes. Further validation studies are necessary to confirm its clinical utility.

Periprosthetic joint infections (PJI) caused by Enterococcus spp., especially vancomycin-resistant strains (VRE), are challenging to treat due to biofilm tolerance and limited antibiotic options. Bacteriophages offer a promising adjunct through targeted and biofilm-disrupting activity. This study evaluated two novel lytic phages, alone and combined with last-line antibiotics, for their ability to eradicate VRE biofilms in vitro. Two novel lytic phages, CUB-FM (E. faecium) and CUB-FS (E. faecalis), were isolated from hospital sewage and characterized via whole-genome sequencing and transmission electron microscopy. Antibiofilm efficacy of phages alone and in combination with dalbavancin, daptomycin, and fosfomycin was assessed against biofilm-embedded VRE strains using isothermal microcalorimetry. Synergy was defined as a combined effect exceeding the sum of individual activities. Genomic analysis confirmed both phages as strictly lytic and free of lysogeny, virulence, or resistance genes. TEM classified CUB-FM within Salasmaviridae and CUB-FS within Herelleviridae. Both exhibited dose-dependent antibiofilm activity, with optimal efficacy at 10¹² (CUB-FM) and 10⁸ PFU/mL (CUB-FS). While antibiotic monotherapies showed limited antibiofilm effects, phage-antibiotic combinations markedly enhanced activity. CUB-FM with dalbavancin achieved the strongest suppression against E. faecium (tMax22.3 h vs. 5.2 h control, P < 0.001), and CUB-FS with dalbavancin or fosfomycin at ≥10 × MIC completely eradicated E. faecalis biofilms. Daptomycin-phage combinations produced additive to synergistic effects. Novel phages CUB-FM and CUB-FS exhibit potent antibiofilm activity and synergize with last-line antibiotics against VRE. Phage-antibiotic combinations, particularly with dalbavancin and fosfomycin, represent a promising strategy for treating biofilm-associated enterococcal PJIs.IMPORTANCEVancomycin-resistant enterococci (VRE) are increasingly implicated in biofilm-associated periprosthetic joint infections, where treatment options are limited, and clinical outcomes are poor. Conventional antibiotics often fail due to reduced biofilm penetration and bacterial tolerance, highlighting the need for novel therapeutic strategies. Our study introduces two newly characterized lytic phages, CUB-FM and CUB-FS, which demonstrated strong antibiofilm activity and synergistic interactions with last-line antibiotics. Notably, phage-antibiotic combinations achieved either additive or synergistic effects, with dalbavancin and fosfomycin-phage therapy leading to a complete eradication of E. faecalis biofilms. These findings provide proof of concept that combining phages with antibiotics enhances efficacy against multidrug-resistant Enterococcus biofilms, offering a translational pathway for personalized, adjunctive therapies in complex orthopedic infections. By bridging the gap between genomic phage safety validation and functional synergy testing, this work supports further preclinical and clinical development of phage-antibiotic strategies for refractory implant-associated infections.

OBJECTIVE:Screw loosening is one of the most frequent complications after instrumented spine surgery, which constitutes a heavy burden for patients and the health care system. Low-virulent colonialization with biofilm formation has been identified as a possible cause for screw loosening. The aim of this study was to investigate the rate of low virulent infections in recurrent screw loosening after revision surgery. METHODS:Seventy-nine patients from January 2015-July 2018 undergoing revision surgery due to clinically aseptic implant loosening were included in our observational study. Sonication of the loosened implant was performed. All identified patients received clinical and radiographic follow-up. Screw loosening was evaluated in computed tomography scans carried out at least 12 months after revision surgery. Patients were differentiated into the following 3 groups: 1) all patients with low virulent colonialization, who received antibiotic treatment (Co + ABX); 2) all patients with colonialization without postoperative antibiotic treatment (Co-ABX); and 3) reference cohort containing all patients without colonialization (noCo). RESULTS:Seventy-nine patients (51 females; mean age, 65.12 years) were identified. Forty-two patients (51.2%) received radiologic follow-up with computed tomography scan for implant control. These patients were assigned to 3 groups (Co + ABX: n = 5 [12%]; Co-ABX: n = 8 [19%]; noCo: n = 29 [69%]). In 10 of 13 patients with positive sonication results (Co + ABX and Co-ABX), recurrent screw loosening occurred (76.9%). Antibiotic administration had no influence on screw loosening rates (4 of 5 patients [80%] in Co + ABX and 6 of 8 [75%] patients in Co-ABX; P > 0.05). In the reference group, noCo, in 11 of 29 patients (37.9%), recurrent screw loosening was identified (P = 0.043). CONCLUSIONS:In patients with screw revision surgery, incidence of low-virulent microorganism colonialization is high and may play a role in the incidence of screw loosening. New therapeutic approaches addressing low-virulent infections and biofilm formation may be helpful.

The diagnosis of periprosthetic joint infection (PJI) remains a challenge, as no single diagnostic test shows high diagnostic accuracy. Recently, the measurement of synovial biomarkers has shown promising results. The aim of this study was to present a novel multiplex micro-enzyme-linked immunosorbent assay (ELISA) method for the rapid and simultaneous measurement of alpha-defensin, interleukin (IL)-6, and calprotectin developed in a model buffer system and human spiked synovial fluid. A microfluidics- and chemiluminescence-based multiplex micro-ELISA point-of-care testing system was employed for the rapid and simultaneous measurement of alpha-defensin, calprotectin, and IL-6 developed in a model buffer system and spiked human synovial fluid. Cut-off values of 1.56 µg/ml for alpha-defensin, 50 µg/ml for calprotectin, and 0.031 µg/ml for IL-6 were extracted from the literature as optimal cut-off values for the diagnosis of PJI, and were used for comparison. Limit of detection (LoD) was determined for each individual biomarker by means of calibration curves with serial dilutions in a model buffer system. LoDs of 0.008, 0.002, and 0.00014 µg/ml were determined for alpha-defensin, calprotectin, and IL-6, respectively. The spiked synovial fluid assay determined LoDs of 0.08, 0.31, and 0.004 µg/ml for alpha-defensin, calprotectin, and IL-6, respectively. These findings highlight the proposed platform’s unique features, including simultaneous measurement of three key synovial biomarkers, minimal sample volume requirements (5 to 50 µl), lower LoDs compared to conventional tests, and a short processing turnaround time of 22 minutes. Further validation studies are necessary to confirm its clinical utility. Cite this article: Bone Joint Res 2025;14(3):176–184.

Aims:The aim of this study was to evaluate the clinical and microbiological characteristics, surgical and antibiotic strategies, and long-term outcomes in patients with polymicrobial periprosthetic joint infection (PJI). Methods:This retrospective cohort study was undertaken at a tertiary healthcare centre and included patients aged ≥ 18 years with polymicrobial PJI treated with two-stage or multistage exchange of implants between January 2013 and May 2020. The modified European Bone and Joint Infection Society (EBJIS) criteria were used for the diagnosis of PJI. Surgical and antibiotic treatment followed a standardized institutional algorithm. Outcomes were assessed using Delphi international multidisciplinary consensus criteria and function was classified into categories of mobility. Statistical analyses included Kaplan-Meier survival curves and logistic regression for the identification of risk factors. Results:A total of 39 patients were included; 24 hip and 15 knee PJIs. Staphylococci (n = 26; 67%), Gram-negative bacilli (n = 15; 38%), and enterococci (n = 14; 36%) were the most frequently isolated pathogens. The median interval between explantation and reimplantation was 91 days, with a median of three revisions required for infection control. Postoperative antibiotic regimens commonly included β-lactams with glycopeptides or lipopeptides, followed by biofilm-active oral antibiotics. The rates of infection-free survival at one, two, and three years were comparable for hip and knee PJIs (76% (95% CI 52 to 89) and 65% (95% CI 31 to 85), respectively; p = 0.121), but there was signicantly better long-term survival after four years for hip PJIs (76% (95% CI 52 to 89) vs 43% (95% CI 9 to 75); p < 0.001). Recurrent infection occurred in ten patients (26%), with difficult-to-treat (DTT) pathogens significantly influencing the failure of treatment. Functional outcomes varied, with 13 patients (33%) regaining independent mobilization. Conclusion:Polymicrobial PJI remains a difficult condition to treat, with high morbidity requiring a tailored multidisciplinary approach. While standardized surgical and antibiotic strategies improve infection control, DTT organisms, and previous revision procedures increase the risk of recurrent infection. The poor long-term functional outcomes highlight the need for further optimization of treatment protocols to enhance patients' mobility and quality of life.

Objectives Antimicrobial suppression improves short-term outcome of streptococcal periprosthetic joint infection (PJI) compared to standard treatment. This study assesses the long-term effectiveness of suppression. Methods This prospective study included consecutive patients with streptococcal PJI. Infection-free survival was analyzed using the Kaplan-Meier method and compared between patients receiving standard therapy (12 weeks) and those with suppression therapy (>6 months) with the log-rank test. Results A total of 63 PJI episodes were analyzed. Standard treatment was administered to 33 patients, while 30 patients received suppression therapy (10 had ongoing and 20 had discontinued suppression at time of follow-up). Predominant pathogens included Streptococcus agalactiae (n=20) and Streptococcus dysgalactiae (n=18). The main surgical procedures used were two-stage exchange (n=35) and prosthesis retention (n=21).At 7.5 years, infection-free survival was significantly higher in the suppression group (62%) compared to the standard therapy group (38%) (p=0.038). Streptococci accounted for 14 of 27 failures (52%). Suppression effectively prevented streptococcal infection during treatment; however, relapses or new streptococcal infections occurred in 5 of 20 patients (25%) after discontinuation. Failures during ongoing suppression were exclusively caused by gram-negative rods. Conclusions Suppression therapy significantly improves long-term outcome in streptococcal PJI. While suppression effectively prevents streptococcal reinfections during treatment, the risk of recurrence reemerges after discontinuation.

Periprosthetic joint infection (PJI) remains a major complication in orthopedic surgery, with accurate and timely diagnosis being essential for optimal patient management. Traditional culture-based diagnostics are often limited by suboptimal sensitivity, especially in biofilm-associated and low-virulence infections. In recent years, non-culture-based methodologies have gained prominence. Molecular techniques, such as polymerase chain reaction (PCR) and next-generation sequencing (NGS), offer enhanced detection of microbial DNA, even in culture-negative cases, and enable precise pathogen identification. In parallel, extensive research has focused on biomarkers, including systemic (e.g., C-reactive protein, fibrinogen, D-dimer), synovial (e.g., alpha-defensin, calprotectin, interleukins), and pathogen-derived markers (e.g., D-lactate), the latter reflecting metabolic products secreted by microorganisms during infection. The development of multiplex platforms now allows for the simultaneous measurement of multiple synovial biomarkers, improving diagnostic accuracy and turnaround time. Furthermore, the integration of artificial intelligence (AI) and machine learning algorithms into diagnostic workflows has opened new avenues for combining clinical, molecular, and biochemical data. These models can generate probability scores for PJI diagnosis with high accuracy, supporting clinical decision-making. While these technologies are still being validated for routine use, their convergence marks a significant step toward precision diagnostics in PJI, potentially improving early detection, reducing diagnostic uncertainty, and guiding targeted therapy.

BackgroundFracture-related infections (FRI), particularly those caused by antibiotic resistant Staphylococcus aureus, present significant clinical challenges due to the formation of biofilm on the implanted device, and reduced options for conventional antibiotic treatment. Bacteriophage (phage) therapy (PT) offers a targeted approach to managing such infections, however, evidence for pharmacokinetics and optimal route of administration is limited for FRI. This study aimed to evaluate safety, phage distribution kinetics, phage neutralization, and antibacterial efficacy after intravenous or local administration in a sheep model.MethodsThe study was conducted in two phases: Phase 1 assessed the safety and distribution of two successive rounds of intravenous and local phage administration in non-infected sheep, while Phase 2 evaluated the therapeutic efficacy of intravenous versus local phage administration in combination with intravenous vancomycin in treating MRSA-induced FRI (tibial osteotomy with plate fixation). The specific pathogen and phage used in the sheep were both taken from a human FRI patient treated with PT. Phage neutralization and phage distribution were the primary outcomes measured in both phases of the sheep study.ResultsBoth intravenous and local phage administration were well-tolerated in non-infected sheep. Phages were cleared rapidly from circulation after intravenous administration, with no phage detected after 240 minutes. Phage neutralization increased during PT, peaking at 99.9% in non-inoculated sheep by the end of the second phage treatment (day 50). In infected sheep, phage neutralization levels reached a maximum of 99.9% earlier (day 13), with no significant differences between intravenous and local administration. The bacterial load was not significantly changed by PT, either IV or locally applied.ConclusionsPT is a safe adjunct to antibiotic treatment for FRI, however, phage neutralization developed rapidly and was accelerated in infected hosts. Further research is required to optimize phage selection, dosing, and delivery methods to enhance its therapeutic potential as an adjunct to conventional antibiotic therapy, particularly in the face of challenges such as rapid clearance and phage neutralization.

Periprosthetic joint infection (PJI) and periprosthetic fracture (PPF) belong to the most devastating and complex complications following total hip arthroplasty, especially when both occur simultaneously. The aims of this study were (1) to evaluate the clinical outcome of PJI treatment in the setting of concomitant PPF and (2) to determine risk factors for reinfection. This study retrospectively analysed PPF occurring during the treatment of PJI in total hip arthroplasty (THA). In total 46 THA were included with concomitant PJI and PPF, of which 28 fractures occurred during the explantation and 13 fractures occurred during the interval between explantation and reimplantation. The median follow-up period was 66 months (range: 24–90) and minimum follow up of at least two years. Patients without infection recurrence after their surgical management were considered to have a successful clinical outcome. Reinfections rates were estimated through Kaplan-Meier curve and potential risk factors for reinfection were analysed with univariate non-parametric tests. Multivariate Cox hazard regression was used in order to account for confounders. Overall, the success rate in our cohort was 71

Musculoskeletal infections (MSKIs) pose significant challenges in orthopedic surgery. These infections are often caused by Staphylococcus aureus and S. epidermidis. Early diagnosis is crucial, as it allows prompt treatment before the infection becomes chronic and more difficult to manage. This study evaluated the expression of microRNAs (miRNAs) in the serum of patients with staphylococcal MSKI and their potential as biomarkers. Serum samples from patients with confirmed staphylococcal MSKI were used for RNA sequencing and validation (n = 24 S. aureus, n = 25 S. epidermidis and n = 25 controls). In S. aureus-infected patients compared to uninfected controls, 23 miRNAs were upregulated and 20 downregulated, while 94 miRNAs were upregulated and 31 downregulated in those infected with S. epidermidis. Validation experiments revealed the upregulation of hsa-miR-1246, hsa-miR-483-5p, and hsa-miR-1290, and the downregulation of hsa-miR-1-3p, hsa-miR-148b-3p, and hsa-miR-23a-3p in S. aureus-infected patients compared to both S. epidermidis-infected patients and uninfected controls. Human peripheral blood mononuclear cells treated in vitro with bacterial culture supernatants exhibited a similar pattern of miRNA expression. Receiver operating characteristic (ROC) curve analyses demonstrated that combining four miRNAs (miR-1246, miR-1290, miR-148b-3p, and miR-23a-3p) achieved a high diagnostic accuracy, with an area under the curve of 0.96, distinguishing S. aureus from S. epidermidis-infected patients. In summary, this study identified four differentially expressed miRNAs in S. aureus-infected patients compared to those with S. epidermidis infections and uninfected controls. These findings allow miRNA to be used as MSKI markers and to study their effect on immune responses during bacterial infections.

The objectives of our study were (1) to determine the success rate of 2-stage total hip arthroplasty (THA) implant exchange for the treatment of periprosthetic joint infection (PJI) and (2) to evaluate relevant risk factors for reinfection and subsequent revision surgeries after reimplantation. After institutional board approval we conducted a prospective analysis of 187 patients who underwent a 2-stage revision THA after being diagnosed with PJI from 2013 to 2019. The mean duration of follow-up was 54.2 ± 24.9 months (>36 months) and the mean duration of 1st to 2nd stage interval was 9.8 ± 8.9 weeks (>2 weeks). All patients remained in a Girdlestone situation without a spacer between the two stages of the treatment. Infection recurrence and reoperation rates were estimated through Kaplan-Meier survival analysis and the investigation for potential risk factors was performed using Cox hazard regression. The overall success rate in our cohort was 85.6% with an estimated cumulative survival of 84% (95% CI = 79.8-89.9%). The estimated risk for reinfection was 9% for the first 6 months, 11.5% for the first year and 14% for the first two years postoperatively. Seven out of 27 reinfections were persistent infections (26%), whereas the remaining 20 (74%) were new infections caused by a different pathogen. DDT (difficult-to-treat) or high virulence pathogens were found to be significant independent risk factors for infection recurrence. (HR=1.31, 95% CI: 1.47-9.36, p=0.006 and HR=1.35, 95% CI: 1.73-8.57, p=0.001). Any history of another previous 2-stage implant exchange of the affected hip was also found to be an independent predictor for re-infection after reimplantation (HR=1.28, 95% CI: 1.33-9.62, p=0.01). Overall reoperation and revision rates were 26.2% and 16.6% respectively during the entire course of the follow up. Re-infected patients had 80% higher probability for reoperation than the non-infected ones (p<0.001, Log-rank= 102.6) and they were 55% more likely to undergo revision surgery during their follow up (p<0.001, Log-rank=55.4). Reinfection rates after 2-stage THA revision for PJI still remain high, especially in affected patients with prior failed 2-stage implant exchange or challenging infections involving high-grade or difficult-to-treat pathogens. PJI recurrence seems to favor new infections caused by different pathogens rather than infections persistence.

INTRODUCTION:Infection is one of the major complications associated with intramedullary nailing. Aim of this study is to analyze the outcome of infection after fixation of tibia and femur with intramedullary nailing and to compare the outcome in patients treated with nail retention versus removal. PATIENTS AND METHODS:This is a retrospective cohort study including consecutive adult patients treated at our institution between 01/2015 and 03/2022 for infection involving the intramedullary nail used for fixation of femur or tibia fractures. Characteristics of infection and outcome data were evaluated by actively contacting the patients with a standardized questionnaire. Uniform predetermined definitions were used. The probability of infection-free survival was estimated using the Kaplan-Meier method and compared between the groups using log-rank test. RESULTS:Fifty-one patients (37 males, 14 females) with infection associated with femur (n = 37) or tibia (n = 14) nail were included. The pathogen was identified in 45 (88 %) episodes, including 30 monomicrobial and 15 polymicrobial infections. The predominant pathogens in monomicrobial infections were coagulase-negative staphylococci (n = 11) and in polymicrobial infections gram-negative bacteria. The intramedullary nail was removed in 35 (69 %) patients and retained in 16 (31 %) patients. At follow-up (median follow-up 28 months; IQR 21-38 months), 19 of 31 (61 %) evaluable patients were infection-free. In patients with nail removal, 14 of 22 (64 %) were infection-free, whereas those with nail retention, 5 of 9 (56 %) were infection free. DISCUSSION:The fact that patients in the nail retention group were of higher age, experienced earlier infection after surgery, and were mainly caused by high virulent pathogens suggest a potential selection bias. Nevertheless, it appears that certain infections may be treated successfully with nail retention, reducing the number of interventions for the patient, and increasing cost effectiveness. CONCLUSIONS:Overall cure of infected intramedullary nails was 61 %. No significant difference in the infection eradication of infected intramedullary nails were observed, irrespective of the time of occurrence after nail implantation. These results should be confirmed in a larger prospective cohort.

BACKGROUND:Fracture-related infection (FRI) is a devastating complication of musculoskeletal trauma. Pain and poor functional outcomes are common, however there is limited insight to the long-term opiate use in this cohort. This study aims to 1) compare the rate of chronic opiate use between trauma patients with and without FRI, and 2) identify risk factors for chronic opiate use among patients with FRI. METHODS:A cohort of adult injured patients hospitalized in Queensland, Australia between 2014 and 2015 undergoing operative fracture management was extracted from the Community Opioid Dispensing after Injury (CODI) study. This included person-linked hospitalization clinical data, community opioid dispensing and mortality. Data were extracted from 3-months prior to the index-hospitalization to 2-years after discharge. Community opioid dispensing was compared for patients with and without FRI. Increased risk of chronic opiate therapy (COT) (≥90 days cumulatively) was examined using multivariable logistic regression, odds ratios (OR) and 95 % Confidence Intervals (95 % CI). RESULTS:There were 19,218 operatively managed orthopaedic trauma patients, of which 394 (2.1 %) were complicated with FRI. Opioids were dispensed post injury for 9399 patients. Patients with FRI were more likely to be prescribed opioids (68 %) than patients without FRI (48.5 %, p < 0.001). COT was associated with FRI, with 29.0 % of infected patients being dispensed opiates >90 days (23.8 % no FRI group, p < 0.001). The median duration of opiate therapy among patients with FRI who were dispensed opiates was 60 days [IQR 15-237] (versus 23 days [IQR 15-84] for no FRI, p < 0.001) and the median end dose was 14 mg oral morphine equivalent for both groups [FRI IQR 10-30; No FRI IQR 10-28]. Among patients with FRI, pre-injury opiates, high injury severity, length of stay >21 days and >2 revision surgeries were associated with COT. CONCLUSION:Infection following trauma surgery is associated with long term opiate use. Risk factors identified for with COT include pre-injury opiate use, high injury severity, increased length of stay and multiple revision surgeries. These insights should be utilised to guide opiate stewardship programs, advocate for improved prevention and treatment strategies for FRI and optimise physical and mental rehabilitation.

Multi-drug resistant Gram-negative pathogens are increasingly difficult-to-treat perpetrators of infections. New, innovative, and more multifaceted therapies for the treatment of multi-drug resistant strains are thus urgent to hinder further drug resistance and mitigate deadly, untreatable infections. Our study aimed to investigate the efficacy of cefiderocol against Gram-negative aerobic bacteria alone and in combination with phages. The minimum inhibitory concentration (MIC) of cefiderocol was determined using the microdilution broth method, while the minimum biofilm bactericidal concentration was assessed using isothermal microcalorimetry. The combined effect of cefiderocol and phages was evaluated using colony-forming unit counts. Results demonstrated a notable antibacterial effect of cefiderocol, with 83.4% of tested strains exhibiting susceptibility. When combined with phages, the MIC of cefiderocol was reduced by 2-64-fold, indicating a synergistic interaction between the two agents. Furthermore, the combination therapy showed enhanced efficacy against biofilm compared to monotherapy with either cefiderocol or phages alone, leading to complete biofilm elimination in certain cases. This study highlights the potential of combining cefiderocol with phages as a strategy to combat multi-drug resistant Gram-negative bacterial infections. The observed synergy suggests that this combination therapy could improve treatment outcomes and help address the challenges of antibiotic resistance and biofilm-associated infections.