Smoking is known to impair wound healing and to increase the risk of peri-operative adverse events and is associated with orthopaedic infection and fracture non-union. Understanding the magnitude of the causal effect on orthopaedic infection recurrence may improve pre-operative patient counselling. Four prospectively-collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for clinically diagnosed orthopaedic infections, were included in logistic regression modelling with Inverse Probability of Treatment Weighting for current smoking status [1–3]. Host factors including age, gender and ASA score were included as potential confounding variables, interacting through surgical treatment as a collider variable in a pre-specified structural causal model informed by clinical experience. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. A subset of 669 participants with positive histology, microbiology or a sinus at the time of surgery, were analysed separately.Aim
Methods
Fracture-related infection (FRI) is treated by adequate debridement, lavage, fracture stabilization (if indicated), adequate soft tissue coverage and systemic antimicrobial therapy. Additional administration of local antibiotics (LA), placed directly in the surgical field, is thought to be beneficial for successful eradication of infection. 1) To evaluate the effect of local antibiotics on outcome in patients with FRI. 2) To evaluate whether bacterial resistance to the implanted local antibiotics influences its efficacy.Background
Aims
Excision of chronic osteomyelitis (cOM) creates a dead space which must be managed to avoid early recurrence of infection. Systemic antimicrobials cannot penetrate this space in high concentration so local therapy has become an attractive adjunct to surgery. This study presents the mid- long-term results of local therapy with gentamicin in a bioabsorbable ceramic carrier. A prospective series of 100 patients with Cierny & Mader Types III and IV cOM, affecting 105 bones, were treated with a single stage procedure, including debridement, deep tissue sampling, local and systemic antimicrobials, stabilization and immediate skin closure. cOM was confirmed with strict diagnostic criteria. Patients were followed up for a mean of 6.05 years (range 4.2–8.4 years).Aim
Method
Recurrence of bone and joint infection, despite appropriate therapy, is well recognised and stimulates ongoing interest in identifying host factors that predict infection recurrence. Clinical prediction models exist for those treated with DAIR, but to date no models with a low risk of bias predict orthopaedic infection recurrence for people with surgically excised infection and removed metalwork. The aims of this study were to construct and internally validate a risk prediction model for infection recurrence at 12 months, and to identify factors that predict recurrence. Predictive factors must be easy to check in pre-operative assessment and relevant across patient groups. Four prospectively collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for orthopaedic infections, were included in logistic regression modelling [1–3]. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. Eight predictive factors were investigated following Aim
Methods
Fracture related infection (FRI) is classically defined as early (0–2 weeks), delayed (3–10 weeks) or late (>10 weeks). Treatment strategies reflect this, particularly with debridement and implant retention (DAIR), but there is little evidence to support this. This multinational study clarified the relationship between pathogens isolated and time from injury. All confirmed FRI cases, managed surgically, at three hospitals were included. Data were analyzed on patient demographics, time from injury and pathogens isolated. Patients who underwent DAIR were also analyzed separately.Aim
Methods
The primary aim of this study was to evaluate the outcomes of fungal knee periprosthetic joint infection following knee arthroplasty. The secondary aim was to evaluate risk factors for acquiring a fungal PJI. This was a retrospective analysis of patients presenting with a confirmed fungal PJI of the knee in two tertiary centres. There were a total of 45 cases. Isolated fungal infections along with mixed bacterial and fungal infections were included. Mean follow up was 40 months (range 3–118).Abstract
Aims
Patients and Methods
To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated.Aim
Method
This study investigated the effect of the choice of antibiotic regime on outcome of patients treated for fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. All patients with FRI, confirmed by the FRI Consensus Definition1 and treated surgically, were included. Data were collected on patient characteristics, microbial cultures, antibiograms, empiric and definitive systemic antibiotic regimes and local antibiotic use. All patients were followed up for at least one year. The primary outcome was eradication of infection. The chosen antibiotic regimes were compared to the recent guidelines from the FRI Consensus Group2, to assess the correlation with outcome.Aim
Method
This study investigated the management and clinical outcomes of patients treated for confirmed fracture-related infection (FRI) at 3 centres, in the UK and the Netherlands between 2015 and 2019. All patients with FRI, confirmed by the FRI Consensus Definition1 and treated surgically, were included. Data were collected on patient characteristics, time from injury to FRI surgery, soft tissue reconstruction, type of stabilization and use of local antibiotics. All patients were followed up for at least one year. The rates of eradication of infection and union were assessed. The associations between treatment methods, time from injury and outcomes were determined.Aim
Method
Metagenomic nanopore sequencing is demonstrating potential as a tool for diagnosis of infections directly from clinical samples. We have previously shown nanopore sequencing can be used to determine the causative bacterial species in prosthetic joint infections (PJI). However, to make predictions regarding antimicrobial resistance, human DNA contamination must be reduced so a greater proportion of sequence data corresponds to the microbial portion of the DNA extract. Here, we utilise selective DNA extraction from sonication fluid samples to begin to make predictions regarding antimicrobial resistance in PJI. We investigated host cell DNA depletion with 5% saponin selective human cell lysis followed by nuclease digestion. Subsequently, bacterial cells were mechanically lysed before DNA extraction. Sequencing libraries from samples treated with and without saponin were prepared with a Rapid PCR Barcoding Kit1 and sequenced in multiplexes of 2–8 samples/flowcell on a GridION. Sequencing reads were analysed using the CRuMPIT pipeline and thresholds to indicate presence of a specific bacterial genus/species were investigated. Antimicrobial resistance determinants were detected using previously published sequences specifically for Aim
Method
Patients with long-bone osteomyelitis are frequently referred with limited microbiological information. This study compared pre-referral microbiology in long bone osteomyelitis with intra-operative microbiology from a specialist centre. All patients referred to a single tertiary centre between February 2019 and February 2020, aged ≥18 years and received surgery for confirmed long-bone osteomyelitis were included. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated.Introduction
Materials and Methods
This study quantified changes in the microbiology of osteomyelitis in a single specialist centre within the UK. The rate of infection with multi-drug-resistant (MDR) bacteria was measured over a ten year period in 388 patients. Patients with confirmed osteomyelitis who received curative surgery from 2013–2017 were included (n=222). Microbiology was compared to patients from a cohort between 2001–2004, using the same diagnostic criteria (n=166).1 The proportion of MDR bacterial pathogens2 from deep tissue culture in these cohorts were compared. Pathogens were analysed according to aetiology and the presence of metal-work.Aim
Method
Current guidelines for the diagnosis of prosthetic joint infection (PJI) recommend collecting 4–5 independent tissue specimens, with isolation of indistinguishable organisms from two or more specimens. The same principle has been applied to other orthopaedic device-related infections (DRI) including fracture-related infections. However there are few published data validating this approach in DRI other than PJI. We evaluated the performance of different diagnostic cutoffs and varying numbers of tissue specimens for microbiological sampling in fracture-related infections. We used standard protocols for tissue sample collection and laboratory processing, and a standard clinical definition of fracture-related infection. We explored how tissue culture sensitivity and specificity varied with the number of tissue specimens obtained; and with the number of specimens from which an identical isolate was required (diagnostic cutoff). To model the effect of the number of specimens taken we randomly sampled Aim
Method
Management of bone and joint infection can be technically complex and often requires a prolonged course of antibiotics. Traditionally, bone and joint infection management utilises nurse-led outpatient parenteral antibiotic therapy (OPAT) where adherence is unlikely to be an issue. However, with increasing evidence in favour of oral therapy, the question of adherence merits further consideration. We describe the adherence of both oral (PO) and self-administered intravenous (IV) antibiotics in the treatment of bone and joint infection using paper questionnaires (8-item Modified Morisky Adherence Score (MMAS)) and, in a subset of participants, electronic pill containers (Medication Event Monitoring Systems*). All eligible participants enrolled in the OVIVA trial (2010–2015) were randomised to six weeks of either PO or IV antibiotic treatment arms. Self-administering patients were followed up with questionnaires at day 14 and 42. A subset of PO participants was also given the medication event monitoring system* in order to validate the adherence questionnaires. The results were correlated with treatment failures at one-year follow-up.Aim
Method
Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting. This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%.Aim
Method
To assess the influence of route of antibiotic administration on patient-reported outcome measures (PROMS) of individuals treated for hip and knee infections in the OVIVA multi-centre randomised controlled trial. This study was designed to determine whether oral antibiotic therapy is non-inferior to intravenous (IV) therapy when given for the first six weeks of treatment for bone and joint infections. Of the 1054 participants recruited from 26 centres, 462 were treated for periprosthetic or native joint infections of the hip or knee. There were 243 participants in the IV antibiotic cohort and 219 in the oral cohort. Functional outcome was determined at baseline through to one year using the Oxford Hip/Knee Score (OHS/OKS) as joint-specific measures (0 the worse and 48 the best). An adjusted quantile regression model was used to compare functional outcome scores.Aim
Method
Culture of multiple periprosthetic tissue samples is the current gold-standard for microbiological diagnosis of prosthetic joint infections (PJI). Additional diagnostic information may be obtained through sonication fluid culture of explants. These current techniques can have relatively low sensitivity, with prior antimicrobial therapy or infection by fastidious organisms particularly influencing culture results. Metagenomic sequencing has demonstrated potential as a tool for diagnosis of bacterial, viral and parasitic infections directly from clinical samples, without the need for an initial culture step. We assessed whether metagenomic sequencing of DNA extracts from sonication fluid can provide a sensitive tool for diagnosis of PJI compared to sonication fluid culture. We compared metagenomic sequencing with standard aerobic and anaerobic culture in 97 sonication fluid samples from prosthetic joint and other orthopaedic device-related infections. Sonication fluids were filtered to remove whole human cells and tissue debris, then bacterial cells were mechanically lysed before DNA extraction. DNA was sequenced and sequencing reads were taxonomically classified using Kraken. Using 50 derivation samples, we determined optimal thresholds for the number and proportion of bacterial reads required to identify an infection and confirmed our findings in 47 independent validation samples.Aim
Method
Advocates of Debridement-Antibiotics-and-Implant-Retention (DAIR) in hip peri-prosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared to revision. However, no evidence supports this. This case-control study's aims were to compare outcome of DAIRs for infected 1° total hip arthroplasty (THA) with outcomes following 1° THA and 2-stage revisions of infected 1° THAs. We retrospectively reviewed all DAIRs, performed for confirmed infected 1° THR (DAIR-Group, n=80), in our unit between 1997–2013. Data recorded included patient demographics, medical history, type of surgery and organism identified. Outcome measures included complications, mortality, implant survivorship and functional outcome using the Oxford Hip Score (OHS). Outcome was compared with 2 control groups matched for gender and age; a cohort of 1° THA (1°-THA-Group, n=120) and a cohort of 2-stage revisions for infection (2-Stage-Revision-Group, n=66).Aim
Method
Eradication of infection in chronic osteomyelitis requires effective dead space management after debridement. Residual bacteria in biofilm may be resistant to normal levels of systemic antibiotic penetrating bone and will contribute to recurrence of osteomyelitis. This study evaluated a new antibiotic-loaded biocomposite in the eradication of chronic infection from bone defects. We report a prospective study of 100 patients with Cierny and Mader types III and IV chronic osteomyelitis, in 105 bones. Osteomyelitis followed open fracture or ORIF of closed fractures in 71%. Nine had concomitant septic arthritis. 80% had comorbidities (Cierny-Mader Class B hosts). Ten had infected non-unions. All patients were treated by a multidisciplinary team with a single-stage protocol including; debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with Cerament G™ and immediate primary skin closure. Stabilisation was required in 21 cases and 5 required joint fusion as part of the initial surgery. Plastic surgical skin closure was needed in 23 cases (18 free flaps). Patients were followed up for a minimum of one year (mean 19.5 months; 12–34).Aim
Patients and Method
Collection of 4–5 independent peri-prosthetic tissue samples is recommended for microbiological diagnosis of prosthetic joint infections. Sonication of explanted prostheses has also been shown to increase microbiological yield in some centres. We compared sonication with standard tissue sampling for diagnosis of prosthetic joint and other orthopaedic device related infections. We used standard protocols for sample collection, tissue culture and sonication. Positive tissue culture was defined as isolation of a phenotypically indistinguishable organism from ≥2 samples; and positive sonication culture as isolation of an organism at ≥50 cfu/ml. We compared the diagnostic performance of each method against an established clinical definition of infection (Trampuz 2011), and against a composite clinical and microbiological definition of infection based on international consensus (Gehrke & Parvizi 2013). 350 specimens were received for sonication, including joint prostheses (160), exchangeable components (76), other orthopaedic hardware and cement (104), and bone (10). A median of 5 peri-prosthetic tissue samples were received from each procedure (IQR 4–5). Tissue culture was more sensitive than sonication for diagnosis of prosthetic joint and orthopaedic device related infection using both the clinical definition (66% versus 57%, McNemar's Χ2 test p=0.016) and the composite definition of infection (87% vs 66%, p<0.001). The combination of tissue culture and sonication provided optimum sensitivity: 73% (95% confidence interval 65–79%) against the clinical definition and 92% (86–96%) against the composite definition. Results were similar when analysis was confined to joint prostheses and exchangeable components; other orthopaedic hardware; and patients who had received antibiotics within 14 days prior to surgery. Tissue sampling appears to have higher sensitivity than sonication for diagnosis of prosthetic joint and orthopaedic device infection at our centre. This may reflect rigorous collection of multiple peri-prosthetic tissue samples. A combination of methods may offer optimal sensitivity, reflecting the anatomical and biological spectrum of prosthetic joint and other device related infections.
