Aim

Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1).

Aim. Efficacious antibiotic treatment is crucial for managing and preventing orthopedic infections due to their complexity and associated risk of treatment failure. Previous reviews on antibiotic target tissue concentrations have primarily focused on static measurements, which may not accurately reflect the dynamic pharmacokinetic/pharmacodynamic (PK/PD) changes encountered in clinical settings. This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings using dynamic sampling methods. Method. In accordance with PRISMA guidelines, a literature search was conducted with a scientific librarian's assistance. PubMed and Embase databases were systematically searched using relevant MeSH terms, entries, and keywords. English-published studies between 2004 and 2023 involving systemic antibiotic administration and dynamic measurements were included. 4467 titles were identified. After title and abstract screening, 77 eligible studies remained. Results. The studies covered clinical and pre-clinical studies on both healthy and infected tissue. Dynamic measurements were obtained from various tissues including bone, intervertebral discs, joints, muscles, and subcutaneous tissue. Microdialysis was the predominant sampling method (98.70%, 76/77). Antibiotics like cefuroxime, linezolid, and vancomycin were extensively studied. Fluoroquinolones, tetracyclines, and most beta-lactams typically presented good tissue penetration in relation to relevant PK/PD-targets. In contrast, glycopeptides, macrolides, and flucloxacillin exhibited poorer penetration. Conclusions. This review provides valuable insights of antibiotic distribution in orthopedically relevant target tissues and settings, which may help improve dosing recommendations and treatment outcomes. Our findings are limited to the investigated dosing regimens and administration methods and depend on the chosen PK/PD target. Many antibiotics still require further research to address the significant knowledge gaps, such as the lack of dynamic evaluations for certain antibiotic types and further investigation across various orthopedic settings and tissues

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

Periprosthetic joint infection (PJI) is a complication of total joint arthroplasty that typically requires revision surgery for treatment. Systemic antibiotics are usually held prior to surgery to improve yield of intraoperative cultures. However, recent studies suggest that preoperative aspirations have a high concordance with intraoperative cultures, which may allow surgeons to initiate antibiotic treatment earlier. The purpose of the study was to investigate the effect of Pre-surgical systemic antibiotic therapy on the bacterial burden within the periprosthetic space and systemic immune reaction.

Aims

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.

Aims

The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.

Aims

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

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.

Aims

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

Aims

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

High doses of intra-articular (IA) antibiotics has been shown to effectively achieve a minimal biofilm eradication concentration which could mitigate the need for removal of infected but well-ingrown cementless components of a total hip arthroplasty (THA). However, there are concerns that percutaneous catheters could lead to multi-resistance or multi-organism peri-prosthetic joint infections (PJI) following single stage THA revisions for PJI.

Eighteen single-stage revision procedures were performed for acute (N=9) or chronic (N=9) PJI following a primary (N=12) or revision (N=6) cementless THA. Modular and loosened components were replaced. All well ingrown components were retained. Two Hickmann catheters were placed in the joint space. Along with intravenous antibiotics, IA antibiotics were injected twice a day for two weeks, followed by 3 months of oral antibiotics.

Per-operative cultures demonstrated 4 multi-bacterial PJIs. None of the patients developed post-operatively an AB related renal or systemic dysfunction. At a mean follow-up of 38 months [range, 8–72] all patients had normal erythrocyte sedimentation rate and white blood cell count. Four had a slightly elevated C-reactive protein but were completely symptom free and did not show any sign of loosening at a mean of 27 months [range, 16–59].

Addition of high doses of IA antibiotics following single-stage revision for PJI in cementless THA, is an effective and safe treatment option that allows for retention of well-ingrown components. We found no evidence for residual implant infection or catheter induced multi-resistance.

Total hip arthroplasty, revision surgery, Periprosthetic Joint Infection, Intra-articular antibiotics

Level 4 (Case series)

Aims

The aims of this study were to report the outcomes of patients with a complex fracture of the lower limb in the five years after they took part in the Wound Healing in Surgery for Trauma (WHIST) trial.

Aims

The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes.

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Periprosthetic joint infection is a serious complication of primary total hip replacement (THR) with significant associated morbidity. In acute infection, Debridement, Antibiotics and Implant Retention (DAIR) may be considered. Current national guidelines recommend a DAIR should be performed by “an experienced arthroplasty surgeon┕ but do not specify the need for this to be a revision arthroplasty surgeon. We investigated outcomes in our NHS Trust of DAIR procedures performed by revision and non-revision arthroplasty surgeons. Infection registry data and patient records were analysed for all DAIR procedures of infected primary THRs between 2017 and 2021. Data collected included details of the primary surgery, the presentation with infection, the DAIR procedure and any subsequent complications including return to theatre at any time point. Routinely collected pre- and post-operative patient reported outcome measures (PROMs) were reviewed. 54 periprosthetic joint infections of primary THRs received a DAIR procedure. 41 DAIRs were performed by a revision surgeon and 13 by non-revision surgeons. There was no significant difference in time from primary THR to presentation with infection, time from presentation to DAIR or pre-operative C-reactive protein between the two groups. In 21 (38.9%) patients the DAIR procedure was classed as a treatment failure; 17 patients (31.5%) returned to theatre for further revision surgery, one (2.4%) died related to infection and three (5.6%) had persistent infection but did not receive further surgery. Treatment failure was significantly higher in the non-revision surgeon group (9/13 (69.2%)) than in the revision surgeon group (12/41 (29.3%)) (p = 0.02). Overall, improvement in PROMs after DAIR was seen at both six and 12 months. The overall success rate of DAIR was 61.1% and there was a sustained improvement in PROMs after surgery. However, there was a significant difference in failure rates between revision surgeons and non-revision surgeons

Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Aims

Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

Aims

Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone.

Aim. To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs). Method. FRI patients treated at a trauma centre between 2001 and 2020 were analysed. The primary outcome was 1-year mortality; mortality associations with FRI organism, depth of involvement, and temporality were investigated with multivariable survival analysis. Healthcare-associated and serological outcomes were reported as secondary outcomes. Results. 311 FRIs with mean age of 67.0 and median Charlson comorbidity index of 0 were analysed. Methicillin-sensitive Staphylococcus aureus (MSSA) (29.9%) was the most frequently implicated organism. The majority of FRIs were deep infections (62.7%). FRIs were diagnosed at a median of 40 (IQR 15–200) days post index surgery. The mean follow-up was 5.9 years. One-year mortality amounted to 17.7%. MSSA FRIs were associated with better survival (adj HR 0.34, 95%CI 0.15–0.76, p=0.008). There was no difference in survivorship between deep or superficial FRI (adj HR 0.86, 95%CI 0.62–1.19, p=0.353) or in relation to onset time (adj HR 1.0, 95%CI 0.99–1.00, p=0.943). Implant removal or debridement alone was performed in 61.7% and 17% respectively. Antibiotics was prescribed for 53 (IQR 23–110) days, and patients were hospitalised for 39 (IQR 19–78) days. CRP and ESR normalised in 70.3% (median 46 days) and 53.8% (median 86 days) patients respectively. Conclusions. Fracture-related infections are associated with significant mortality and morbidity regardless of depth and temporality. Non-MSSA FRIs are associated with inferior survival

Aims. Fracture-Related Infection (FRI) is a severe complication caused by microbial infection of bone. It is imperative to gain more insight into the potentials and limitations of Debridement, Antibiotics and Implant Retention (DAIR) to improve future FRI treatment. The aims of this study were to: 1) determine how time to surgery affects the success rate of DAIR procedures of the lower leg performed within 12 weeks after the initial fracture fixation operation and 2) evaluate whether appropriate systemic antimicrobial therapy affects the success rate of a DAIR procedure. Methods. This multinational retrospective cohort study included patients of at least 18-years of age who developed an FRI of the lower leg within 12 weeks after the initial fracture fixation operation, between January 1st 2015 to July 1st 2020. DAIR success was defined by the absence of recurrence of infection, preservation of the affected limb and retention of implants during the initial treatment. The antimicrobial regimen was considered appropriate if the pathogen(s) was susceptible to the given treatment at the correct dose as per guideline. Logistic regression modelling was used to assess factors that could contribute to the DAIR success rate. Results. A total of 120 patients were included, of whom 70 DAIR patients and 50 non-DAIR patients. Within a median follow-up of 35.5 months, 21.4% of DAIR patients developed a recurrent FRI compared to 12.0% of non-DAIR patients. The DAIR procedure was successful in 45 patients (64.3%). According to the Willenegger and Roth classification, DAIR success was achieved in 66.7% (n=16/24) of patients with an early infection (<2 weeks), 64.4% (n=29/45) of patients with a delayed infection (2–10 weeks) and 0.0% (0/1) of patients with a late infection (>10 weeks). Univariate analysis showed that the duration of infection was not associated with DAIR success in this cohort (p=0.136; OR: 0.977; 95%CI: [0.947–1.007]). However, an appropriate antimicrobial regimen was associated with success of DAIR (p=0.029; OR: 3.231; 95%CI: [1.138–9.506]). Conclusions. Although the results should be interpreted with caution, an increased duration of infection was not associated with a decreased success rate of a DAIR procedure in patients with FRI of the lower leg. The results of this study highlight the multifactorial contribution to the success of a DAIR procedure and emphasize the importance of adequate antimicrobial treatment. Therefore, time to surgery should not be the only key-factor when considering a DAIR procedure to treat FRI