Aim. Antimicrobial peptides occur naturally in our intrinsic immune system. PLG0206 is a novel, engineered, 24-amino acid peptide which has broad-spectrum antimicrobial activity, including in biofilm and against multi-drug resistant pathogens (1,2). This is the first clinical study to evaluate the safety and tolerability of PLG0206 when administered via an irrigation solution in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA) during debridement, antibiotics, and implant retention (DAIR). Secondary objectives were to evaluate pharmacokinetics (PK), biomarkers and initial clinical efficacy at one year post-DAIR procedure. Method. This prospective, multicenter, open-label, interventional study assessed two dose levels of PLG0206. Fourteen patients underwent revision for PJI after TKA. At the end of debridement, they received a single intra-articular irrigation of PLG0206 into the wound cavity lasting 15 minutes at concentrations of 3 mg/mL (n=7) or 10 mg/mL (n=7). Patients received post-operative care and intravenous/oral antimicrobial therapy as per their institutional guidelines. Patients were monitored for safety and signs of relapse or persistent infection for 12 months post study drug administration and PK and blood biomarkers were assessed. Results. All patients completed their final study assessment at Day 365. Over the 1-year follow-up, only one recurrence (7%) was noted at Day 169 in the low-dose cohort. Following dosing, nine patients (64.3%) had limited systemic exposure; maximum plasma concentration occurred 1-hour post-administration and declined rapidly to undetectable levels by 24 hours following treatment in all patients. The incidence of drug related treatment-emergent adverse events (TEAEs) was low. Two patients, both in the higher dose cohort, experienced a transient drug related TEAE; one of hypertransaminasaemia and one of neuralgia. Both events were moderate in severity and resolved within two weeks of onset. Conclusions. A single 15-minute irrigation of PLG0206 into the wound cavity of patients undergoing a DAIR procedure for PJI following TKA, is safe and well tolerated by patients. This new antimicrobial peptide offers a promising therapeutic option in musculoskeletal infection. The initial clinical efficacy is encouraging but now needs to be investigated in a much larger clinical trial

Aim. Haematogenous prosthetic joint infections account for 20-35% of total prosthetic infections. Debridement, antibiotics and implant retention (DAIR) is a well-accepted treatment for these infections and probably the most desired by surgeons, since it tries to maintain a functional and stable implant. However, the risk of DAIR failure is not negligible and some risk factors have been described, and also, different scores, such as CRIME80. Nonetheless, less is known about the impact of positive blood cultures may have on DAIR treatment. The aim of our study is to analyze whether the presence of a positive culture is a risk factor for DAIR failure. Method. A retrospective cohort study of 50 late acute haematogenous TKA infections was performed from 2015 to 2023. DAIR failure was defined as the need of a subsequent intervention either a new DAIR or a revision surgery. So, patients were divided into two groups depending on the surgical outcome: successful (SG) vs failure (FG). Demographic variables including age, gender, affected side and body mass index were collected. Patient's comorbidities were also collected including chronic obstructive pulmonary disease (COPD), diabetes, rheumatoid arthritis (RA), cirrhosis and chronic renal failure, etc. Other variables, such as ones included in CRIME80 (C-reactive protein (CRP) >150mg/dl and polyethylene exchange), were also collected. Results. 30 patients had a successful DAIR outcome (60%). Age and sex do not act as risk factors [OR 0.7 (0.2-2.6) and OR 0.4 (0.1-1.3)]. Neither do COPD [OR 3.3 (0.5-2.0), p=0.2]; RA [OR 0.8 (0.2-3.1), p=0.7]; CRP value [3.2 (0.9-11.2), p=0.06]; and polyethylene exchange [OR 0.4 (0.1-2.5), p= 0.3]. Thirty-five blood cultures (70%) were obtained before surgery (20 SG and 15 FG). Nine of the obtained blood cultures were positive (25.7%), being 7 from FG (46.7%) [OR 7.6 (1.3-4.8), p=0.02]. A logistic regression was performed where positive blood cultures were the only significant variable to predict DAIR failure (OR 12, 95% CI 1.1−18, p=0.049), after adjusting for all CRIME80 variables. Skin and soft tissue origin was described in 5 of the nine positive blood cultures (55.6%). Cardiovascular system was the second most common spread (22.2%), and then followed by urogenital and digestive tract. The most common microorganism in FG was Staphylococcus aureus (57.1%) [OR 6.4 (0.2-18.0), p=0.2]. Conclusions. Positive blood cultures may be another risk factor for DAIR failure. This can be important in diagnosis and it may be taken into account in antibiotic and surgical treatment strategies

Aim. This study aims to evaluate the effectiveness of a pre-formulated irrigation solution. 1. (containing ethanol, acetic acid, sodium acetate, benzalkonium chloride, and sterile water) compared to saline solution in managing acute periprosthetic joint infections (A-PJI) during Debridement, Antibiotic, and Implant Retention (DAIR) surgeries. The primary objective is to assess the healing rate using this solution. 1. versus saline in A-PJI patients, with “cure” defined by a set of criteria including no recurrence, wound issues, or need for ongoing suppressive antibiotics after 1 year. Principio del formularioFinal del formulario. Method. This single-center, randomized controlled trial will involve patients with acute periprosthetic infections undergoing standard DAIR surgery, divided into two groups: one receiving saline solution and the other receiving pre-formulated solution. 1. The study is single-blinded, with patients unaware of their group assignment. The study is registered at ISRCTN: https://doi.org/10.1186/ISRCTN10873696. Inclusion criteria include patients over 18 with hip or knee prostheses suffering from acute or hematogenous periprosthetic infections, while exclusion criteria include a history of prior debridement or multiple infected implants, among others. Principio del formularioFinal del formulario A total of 50 subjects are needed for statistical significance, with a 5% dropout rate anticipated. An interim safety analysis will assess early effectiveness and adverse effects, and the results are presented in this study. Data will be managed in online databases and analyzed using SPSS software, with a significance level of p<0.05. Results. Twenty-four patients were eligible for analysis, twelve in each group. The overall average age was 75 years, and the gender distribution was predominantly female (9 F and 3 M in each group). No significant differences were found at the baseline characteristics level between the two groups (p>0.05). The minimum follow-up of 1 year was achieved in all cases except three due to deaths not related to periprosthetic infection. Regarding efficacy, a non-statistically significant difference was observed (p>0.05), with 58% in the serum group and 42% in the pre-formulated irrigation solution. 1. group (X. 2. = 0.17, p=0.683). The average hospital stay was 38.42 days (SD 26.32) in the pre-formulated irrigation solution group. 1. and 24.42 days (SD 18.72) in the serum group, with this difference being not significant (t=1.5, p=0.148). Conclusions. While the current analysis indicates no significant differences between both groups in terms of efficacy, the study's ongoing progress and the inclusion of a larger sample size could potentially yield more definitive results

Aim. Periprosthetic Joint Infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The “JS BACH” classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The “JS BACH” classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand. Method. We applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use. Results. Individual cases were classified as per JS-BACH into “1 - uncomplicated” (n = 268), “2 - complex” (n = 330), and “3 - limited options” (n = 55). This cohort was similar to the original JS-BACH population in terms of baseline characteristics. However, there was a difference in complexity, with more DAIR procedures, fewer revision procedures, and a higher proportion of uncomplicated patients in the PIANO cohort. The risk of treatment failure correlated strongly with the JS-BACH category, with odds ratios (95% CI [confidence interval]) for category 2 versus 1 of 1.75 (1.24 to 2.47) and for category 3 versus 1 of 7.12 (3.42 to 16.02). Conclusions. Despite the PIANO study population being less complicated than the original derivation cohort, the JS-BACH classification showed a clear association with treatment failure in this large external cohort

Aim. Predicting success of a Debridement, Antibiotics and Implant Retention (DAIR) procedure for Periprosthetic Joint Infection (PJI) remains a challenge. A failed DAIR might adversely affect the outcome of any future revision surgery for PJI. Hence, the ability to identify and optimise factors predictive of DAIR success would help target the procedure to the appropriate patient cohort and avoid unnecessary surgery for patients where a DAIR is unlikely to eradicate infection. Method. A retrospective review of our prospective Bone Infection Group database was performed to identify all patients who underwent a DAIR of their hip or knee arthroplasty. Diagnosis of PJI was confirmed using the Musculoskeletal Infection Society (MSIS) 2013 and the European Bone and Joint Infection Society (EBJIS) 2021 classification systems. DAIR surgery was grouped into “successful” or “unsuccessful” outcomes as per the MSIS working group outcome-reporting tool. Results. Sixty-Four consecutive patients with an acute PJI underwent a DAIR procedure between 2009 and 2020. Treatment was successful in 44 (69%). The chance of a successful DAIR was significantly greater if performed within one week of symptom onset compared to greater than one week duration (adjusted odds ratio (OR 0.11; p=0.027; 95% CI [0.02- 0.78]). The chances of a successful DAIR was not influenced by whether the surgeon was an arthroplasty or non-arthroplasty surgeon (OR 0.28; p=0.13; 95% CI [0.05- 1.48]). Isolated Streptococcus infection had a success rate of 100%; followed by Coagulasenegative Staphylococci 71% and Methicillin-susceptible Staphylococcus Aureus 65%. Polymicrobial infection had the worst outcome with a success rate of 47%. Conclusions. In our experience DAIR surgery performed within one week of symptom onset, significantly increased chances of successful infection eradication. Collaborative work is required to ensure arthroplasty patients access prompt appropriate surgical decision-making, remove barriers to early assessment and minimise delays to surgery

Aim. Rifampicin and fluoroquinolone based therapy is generally considered as first-choice targeted oral antimicrobial therapy for staphylococcal prosthetic joint infections (PJI) treated with debridement, antibiotics and implant retention (DAIR). Alternative equally effective antimicrobial strategies are urgently needed due to toxicity and drug-drug interactions that frequently occur with this strategy. Data from recent clinical studies suggests equipoise for other antimicrobial treatment regimens. The objective of the Rifampicin Combination Therapy versus Targeted Antimicrobial Monotherapy in the Oral Antimicrobial Treatment Phase of Staphylococcal Prosthetic Joint Infection (RiCOTTA)-trial is to evaluate whether monotherapy with clindamycin is non-inferior to rifampicin/fluoroquinolone combination therapy in patients with staphylococcal PJI that are treated with DAIR. Method. The RiCOTTA-trial is a multicenter, non-inferiority, open-label, randomized controlled trial evaluating clindamycin versus rifampicin/fluoroquinolone combination therapy in the oral treatment phase in patients with staphylococcal PJI managed with DAIR. The trial is performed in 16 hospitals in the Netherlands. Eligible patients are adults with staphylococcal knee or hip PJI managed by DAIR. Patients are included one to six days before antibiotic treatment is switched from intravenous to oral therapy. Patients with a contraindication for rifampicin, with a megaprosthesis or who receive intravenous antibiotics for more than three weeks after initial debridement are excluded. Primary outcome is treatment success one year after finishing antimicrobial treatment. Success is defined as the absence of: i. Infection related re-surgery, ii. New episode of antibiotic treatment for infection of the index joint after the initial treatment phase of 12 weeks, iii. Ongoing use of antibiotics for the index joint at the end of follow-up, iv. Death. The estimated treatment success of rifampicin combination therapy is 85% and the monotherapy strategy is considered not inferior when the difference in treatment success will be less than 10%. Enrolment of 158 patients per group (316 in total) is needed to confirm non-inferiority of monotherapy with a power of 80%. The trial is currently open for enrolment. The study is approved by the Medical Ethics Committee Leiden, the Hague, Delft, the Netherlands and registered under EU trial number 2022-501620-26-00 in Clinical Trial Information System. Conclusions. Currently, the RiCOTTTA study is the largest randomised clinical trial that compares targeted oral monotherapy with rifampicin combination treatment for staphylococcal PJI. Noninferiority of monotherapy would result in a change in national PJI guidelines and enable clinicians to use a more patient-tailored approach when considering antibiotics for patients during the oral treatment phase of PJI

Introduction. In recent years, many studies demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopaedic related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods. We conducted a retrospective observational multicenter study in patients diagnosed with an early postoperative PJI (i.e less than 3 months after the index arthroplasty) treated with debridement, antibiotics and implant retention (DAIR). Patients from Europe and the USA were included. These two cohorts served as a quasi-randomised trial since an early oral antibiotic switch is routine practice in Europe versus a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for: i) a second DAIR, ii) implant removal, iii) suppressive antibiotic treatment or iv) infection related death. Results. A total of 668 patients were included. 277 received IV antibiotics for <14 days, 232 were given IV antibiotics between 14 - 27 days and 159 received IV antibiotics for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4% and 42.1%, respectively (P 0.80), and mainly comprised the need for a second DAIR. The results did not change when analyzing patients with or without obesity, the causative microorganism or the type of oral antibiotics. Conclusion. In early postoperative PJIs, a longer duration of IV antibiotic treatment is not associated with a lower failure rate of a DAIR procedure

Aim. Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA) whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR), while late infections with two-stage revision surgery. Two-stage revision is considered the “gold standard” for treatment of chronic PJI. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to- lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII)], systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Method. A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII and AISI) were evaluated at the explantation time, at 4, 6, 8 weeks after surgery and at reimplantation time. Correlation between laboratory parameters and surgery success was evaluated, defined as infection absence/resolution at the last follow up. Results. 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nineteen patients completed the two-stage revision process. Among them, none showed signs of re-infection or persistence of infection at the last available follow up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others were submitted to Girdlestone technique or chronic suppressive antibiotic therapy. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7, p-value 0.04) and MLR values (mean 0.4 SD 0.2, p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation of SIRI and PCR, also defined respectively delta-SIRI (mean −2.3 SD 1.8, p-value 0.03) and delta-PCR (mean −46 SD 35.7, p-value 0.03), were associated with favorable outcomes. Conclusions. The results of our study suggest that, in patients with PJI undergoing two-stage, SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant

Aim. Debridement, antibiotics and implant retention (DAIR) is recommended for acute postoperative and late acute prosthetic joint infection (PJI). There are two recommend scores to predict its outcome, KLIC and CRIME 80 scores respectively. They have not been widely adopted for decision making. We aim to evaluate them in predicting DAIR failure in our cohort. Method. All patients submitted to DAIR after total hip or knee PJI, between 2010 and 2021, with a minimum one-year follow-up, were retrospectively evaluated. We excluded tumoral total joint replacements. KLIC score was applied to acute PJIs and CRIME 80 to late acute (LA) PJI. LA PJI was defined as the development of acute symptoms occurring ≥ 3 months after implantation. Repeat DAIR was performed as needed. Failure was defined as the need for implant removal, amputation, infection related death and suppressive antibiotic therapy. Results. We included 102 patients. The overall failure rate was 35.5% (36/102). There was no significant difference for the rate of failure in patients that had one DAIR and those who repeated DAIR - 32.5% (26/80) vs. 45.5% (10/22) (p=0.26). There were no significant correlations between KLIC or CRIME 80 scores and failure rates (p=0.54 and p=0.93 respectively, figure 1). Focusing specifically on the cohort who underwent repeat DAIR (n=22), KLIC and CRIME-80 score were also not associated with failure (p= 0.44 and p=0.50 respectively, figure 1). No host, pathogen or antibiotic treatment related factors were found to predict failure. Conclusions. In our cohort KLIC- and CRIME-80 scores failed to be predictive of DAIR failure, even in the cohort that needed repeat DAIR. We were unable to find any independent failure risk factors. For any tables or figures, please contact the authors directly

Periprosthetic joint infection represents a devastating complication after total elbow arthroplasty. Several measures can be implemented before, during, and after surgery to decrease infection rates, which exceed 5%. Debridement with antibiotics and implant retention has been reported to be successful in less than one-third of acute infections, but still plays a role. For elbows with well-fixed implants, staged retention seems to be equally successful as the more commonly performed two-stage reimplantation, both with a success rate of 70% to 80%. Permanent resection or even amputation are occasionally considered. Not uncommonly, a second-stage reimplantation requires complex reconstruction of the skeleton with allografts, and the extensor mechanism may also be deficient. Further developments are needed to improve our management of infection after elbow arthroplasty.

Cite this article: Bone Joint J 2024;106-B(11):1321–1326.

Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

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The aim of this study was to determine whether obesity had a detrimental effect on the long-term performance and survival of medial unicompartmental knee arthroplasties (UKAs).

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The outcomes of patients with unexpected positive cultures (UPCs) during revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. The objectives of this study were to establish the prevalence and infection-free implant survival in UPCs during presumed aseptic single-stage revision THA and TKA at mid-term follow-up.

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We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Aims. Our aim was to estimate the total costs of all hospitalizations for treating periprosthetic joint infection (PJI) by main management strategy within 24 months post-diagnosis using activity-based costing. Additionally, we investigated the influence of individual PJI treatment pathways on hospital costs within the first 24 months. Methods. Using admission and procedure data from a prospective observational cohort in Australia and New Zealand, Australian Refined Diagnosis Related Groups were assigned to each admitted patient episode of care for activity-based costing estimates of 273 hip PJI patients and 377 knee PJI patients. Costs were aggregated at 24 months post-diagnosis, and are presented in Australian dollars. Results. The mean cost per hip and knee PJI patient was $64,585 (SD $53,550). Single-stage revision mean costs were $67,029 (SD $47,116) and $80,063 (SD $42,438) for hip and knee, respectively. Two-stage revision costs were $113,226 (SD $66,724) and $122,425 (SD $60,874) for hip and knee, respectively. Debridement, antibiotics, and implant retention in hips and knees mean costs were $53,537 (SD$ 39,342) and $48,463 (SD $33,179), respectively. Suppressive antibiotic therapy without surgical management mean costs were $20,296 (SD $8,875) for hip patients and $16,481 (SD $6,712) for knee patients. Hip patients had 16 different treatment pathways and knee patients had 18 treatment pathways. Additional treatment, episodes of care, and length of stay contributed to substantially increased costs up to a maximum of $369,948. Conclusion. Treating PJI incurs a substantial cost burden, which is substantially influenced by management strategy. With an annual PJI incidence of 3,900, the cost burden would be in excess of $250 million to the Australian healthcare system. Treatment pathways with additional surgery, more episodes of care, and a longer length of stay substantially increase the associated hospital costs. Prospectively monitoring individual patient treatment pathways beyond initial management is important when quantifying PJI treatment cost. Our study highlights the importance of optimizing initial surgical treatment, and informs treating hospitals of the resources required to provide care for PJI patients. Cite this article: Bone Joint J 2024;106-B(10):1084–1092

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Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context.

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This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification.

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The optimal bearing surface design for medial unicompartmental knee arthroplasty (UKA) remains controversial. The aim of this study was to compare outcomes of fixed-bearing (FB) and mobile-bearing (MB) UKAs from a single high-volume institution.

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Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction.

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This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.