Antimicrobial-loaded PMMA bone cement has been used since the 1970s as both a fixation material and a local antimicrobial reservoir. Its clinical roles differ between prophylaxis in primary arthroplasty and treatment of established infection, particularly during revision surgery and through the use of temporary spacers. Commercially manufactured products offer more predictable handling, but bespoke admixing may be considered when resistant or unusual organisms are encountered. This Viewpoint argues that such practice requires clearer governance. Cement formulation, antimicrobial choice, dose and mixing technique influence elution, bioactivity, mechanical strength and toxicity. Local delivery may support antimicrobial stewardship, but prolonged low-level elution could theoretically select for resistance if poorly planned. We propose a cautious, evidence-informed framework to support multidisciplinary decision-making and the development of PMMA-specific antimicrobial guidance.

To report the first UK case of bacteriophage (phage) therapy used alongside Debridement, Antibiotics, and Implant Retention (DAIR) for chronic Staphylococcus aureus knee prosthetic joint infection (PJI). An 81-year-old male with a history of ischaemic heart disease with residual mural thrombus, asthma and a left primary knee replacement 32 years prior which was revised to a mega-C distal femoral endoprosthesis in 2019 due to femoral loosening. One year later, the patient developed Staphylococcus aureus PJI with discharging sinuses. A two-stage revision was contraindicated due to anaesthetic risk and he declined amputation. He underwent a DAIR in 2021, arthroscopic washout in 2022 and drainage of a posterior abscess in 2023. Long-term suppression with doxycycline and co-trimoxazole failed to control symptoms and he continued to experience three persistently discharging sinuses. Suppression options were significantly limited due to multiple antibiotic allergies and intolerances (clindamycin, rifampicin, dalbavancin and penicillin) making effective long-term medical management unfeasible. In October 2023, his case was referred to the UK Clinical Phage Network for Bone and Joint Infection and following MDT review, the patient was selected for salvage phage therapy with DAIR to control persistent sinus output. Phage ISP (10 9 PFU/mL) was selected following susceptibility and phage-antibiotic synergy testing at Queen Astrid Military Hospital, Belgium. In October 2024, after local hospital and regulatory import approvals, 10 9 PFU/ml of phage was administered intra-articularly during DAIR with local antibiotic delivery of daptomycin and meropenem via a local hydrogel carrier (DAC). Systemic intravenous daptomycin and meropenem were initiated after deep tissue sampling . S. aureus was grown in 5/7 samples with multiple colonial variants identified. The patient was switched to long-term oral cefalexin and azithromycin. He experienced one episode of fever 48 hours post-operatively, which resolved spontaneously. Two further ultrasound-guided intra-articular injections of phages (10 9 PFU/ml) were administered on days D7 and D14, with no adverse events. All sinuses closed initially; two later reopened within 4 weeks and discharged intermittently. At 3 months, joint aspiration cultures (whilst on antibiotics) were negative. At 6 months, the patient reported reduced leg and knee swelling but persistent drainage from 2 sinuses. This case demonstrates the feasibility of delivering phage therapy in a UK setting with the support of a Clinical Phage Network, despite a 13-month delay. Partial symptom control was achieved, though S. aureus colonial variants may have contributed to reduced treatment response and further evaluation for phage resistance is in progress.

Dalbavancin is a lipoglycopeptide with a half-life of 14 d, significantly reducing the need for daily antibiotic dosing. Although dalbavancin is approved for acute bacterial skin and skin structure infections, its off-label use in complex musculoskeletal infection (MSKI) is increasing. Evidence on its effectiveness for MSKI, especially in facilitating early discharge for patients unsuitable for oral or OPAT (outpatient parenteral antimicrobial therapy) treatments, is limited. This multi-centre observational study aims to evaluate dalbavancin's role in facilitating discharge and improving clinical outcomes in MSKI. Method: this study included adult patients treated with dalbavancin between January 2017 and December 2022 across five hospitals in the UK and France. Data on patient demographics, clinical characteristics, microbiology and treatment outcomes were collected using a standardised form. The study also compared treatment costs between dalbavancin and hypothetical alternatives involving either inpatient care or OPAT. Clinical success was defined as the absence of definite failure based on the OVIVA (oral versus intravenous antibiotics) trial criteria. Results: a total of 39 patients were included, with a median age of 51 years (interquartile range (IQR) 40–72). Prosthetic joint infections (38 %) and septic arthritis (31 %) were the most common indications for dalbavancin use. The primary pathogens identified were Staphylococcus aureus (51 %) and coagulase-negative staphylococci (44 %). Dalbavancin was primarily chosen due to poor adherence or lack of OPAT options in 77 % of cases and for convenience in 23 %. In the necessity group, the use of dalbavancin resulted in a median cost saving of GBP 8894 per patient, and 31 inpatient days were avoided. Of the 32 patients (82 %) assigned a definite outcome, 72 % achieved clinical success. No significant adverse drug reactions were reported. Conclusion: this study fills an important evidence gap by demonstrating that dalbavancin is a viable and cost-effective option for MSKI patients that are unsuitable for oral or OPAT treatments. Dalbavancin facilitates early discharge, reduces hospital stays and achieves comparable clinical outcomes to conventional therapies.

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

This article discusses the recent regulatory restrictions on the use of fluoroquinolones and their impact on treating orthopaedic infections. We focus on the balance between the benefits and risks of fluoroquinolones in scenarios involving severe infections where alternative antibiotics may be less effective. The discussion includes a summary of recent evidence on adverse effects and the implications for clinical practice.

Aim Dalbavancin is a lipoglycopeptide with a half-life of 14 days (range 6.1 to 18.4), significantly longer than other antimicrobials, which avoids the need for daily antibiotic dosing. This multi-centre observational study aims to describe the use of dalbavancin to facilitate discharge in treating bone and joint infections. Method All adult patients treated with dalbavancin from January 2017 to September 2022 in four UK bone infection units were included. Data collected through a standardised data collection form included: Clinical and microbiological characteristics. Hospital length of stay. Complications. Patient suitability for hypothetical treatment options, such as Outpatient Parenteral Antibiotic Team (OPAT) Clinical outcome. Treatment-related costs were calculated for dalbavancin and the preferred hypothetical treatment option that would have been administered for the same duration. The costs were subtracted to calculate the cost difference. Clinical success was defined as the absence of definite failure in accordance with the OVIVA Trial protocol. Results Thirty-six patients were included: 20 males and 16 females, with a median age of 53 (IQR 43–73): Thirteen were septic arthritis, twelve were prosthetic joints, seven were spondylodiscitis and five were other orthopaedic-related implant infections. In twenty cases the infecting organism was Staphylococcus aureus, fourteen were due to coagulase-negative staphylococci and two no cultured organism. Reasons for dalbavancin The reasons for choosing dalbavancin over alternatives were due to either: Necessity due to poor adherence (21), or lack of viable OPAT options due to antibiotic resistance or intolerance (7) OR Convenience to avoid the need for OPAT (8) Dalbavancin was initiated at 1500mg after a median of 12 days (IQR 6–17) of in-hospital antimicrobial therapy. Subsequent dalbavancin doses were based on clinical decisions and ranged from 1000mg to 1500mg. Healthcare benefits Switching to dalbavancin reduced treatment costs by a median of £3526 (IQR 1118 - 6251) compared with the preferred theoretical alternatives. A median of 31 hospital days (IQR 23–47) was avoided among patients who would have required a prolonged inpatient stay. Outcome Overall, 20 patients (55.6%) were successfully treated after a median follow-up of 8 months (IQR, 5.8 – 18.4). No patients developed an adverse drug reaction. Conclusions Dalbavancin can safely facilitate outpatient treatment in patients with limited oral options and in whom OPAT is unsuitable. Dalbavancin is cost-effective compared with the alternative of an inpatient stay.

Objectives: To compare prosthetic joint infection (PJI) and acute kidney injury (AKI) rates among cohorts before and after changing our hospital's antimicrobial prophylactic regimen from cefuroxime to teicoplanin plus gentamicin. Methods: We retrospectively studied all patients undergoing primary total joint arthroplasty at our hospital 18 months pre- and post-implementation of the change in practice. All deep infections identified during follow-up were assessed against the European Bone and Joint Infection Society (EBJIS) definitions for PJI. Survival analysis using Cox regression was employed to adjust for differences in baseline characteristics and compare the risk of PJI between the groups. AKIs were identified using pathology records and categorized according to the KDIGO (Kidney Disease - Improving Global Outcomes) criteria. AKI rates were calculated for the pre- and post-intervention periods. Results: Of 1994 evaluable patients, 1114 (55.9 %) received cefuroxime only (pre-intervention group) and 880 (44.1 %) patients received teicoplanin plus gentamicin (post-intervention group). The overall rate of PJI in our study was 1.50 % (30 of 1994), with a lower PJI rate in the post-intervention group (0.57 %; 5 of 880) compared with the pre-intervention group (2.24 %; 25 of 1114). A corresponding risk reduction for PJI of 75.2 % (95 % CI of 35.2-90.5; p=0.004) was seen in the post-intervention group, which was most pronounced for early-onset and delayed infections due to coagulase-negative staphylococci (CoNS) and cefuroxime-resistant Enterobacteriaceae. Significantly higher AKI rates were seen in the post-intervention group; however, 84 % of cases (32 of 38) were stage 1, and there were no differences in the rate of stage-2 or -3 AKI. Conclusions: Teicoplanin plus gentamicin was associated with a significant reduction in PJI rates compared with cefuroxime. Increases in stage-1 AKI were seen with teicoplanin plus gentamicin.

Abstract Background Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence. Methods This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected. Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection. Results The cohort included 99 patients with a median age of 44 years (29–58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma. One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%. Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation. Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43–9.30; P < 0.001); significantly compromised soft tissue status (HR 4.41: 95%CI 2.18–8.92; P = 0.001); and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73–19.52); P = 0.01). Conclusions Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment.

In this single centre cohort study we assessed BNT162B2 vaccine uptake and effectiveness among UK healthcare workers (HCWs) during a time of high community COVID-19 prevalence. Early uptake among HCWs was 62.3% (1409/2260), however there were significant differences in uptake between age groups, ethnic origins, and job roles. Uptake increased to 72.9% after a vaccine hesitancy working group implemented specific measures. In the 42 days after vaccination, 49 new cases of COVID-19 were identified, of which 7 (14.3%) occurred in HCWs who were beyond 10 days of vaccination. Kaplan–Meier curves for partially vaccinated and unvaccinated groups were congruent until day 14 and continued to diverge up to 42 days. Cox regression analysis showed a 70.0% (95%CI 6.0–91.0; p =0.04) risk reduction for COVID-19 infection in partially vaccinated HCWs. Here we report early vaccination rates among HCWs are generally high although uptake is lower in certain groups. It is possible to improve vaccine uptake and efforts should focus on this, however, significant resource is required. The BNT162B2 vaccine is effective from 14 days post-vaccination in a frontline clinical setting and protection continues beyond 21 days post 1st dose without a 2nd dose, being given.

BACKGROUNDThe Oral Versus Intravenous Antibiotics (OVIVA) Trial demonstrated that oral therapy, when used during the initial 6 weeks in the treatment in bone and joint infection (BJI), is noninferior to intravenous therapy. To date there are no reports describing reproducibility of these findings in a real-world setting.METHODSWe studied all patients diagnosed with BJI at our hospital 12 months pre- and postimplementation of the OVIVA trial findings into clinical practice. An infection consultant recommended antibiotic treatment and patients were followed up by an outpatient parenteral antibiotic therapy (OPAT) service. Prospective data from a local registry was used to analyze baseline clinical details, outcome, length of hospital stay (LOS), and costs.RESULTSA cohort of 328 patients (145 pre- and 183 postimplementation) was analyzed. Postimplementation, 66.1% of patients were switched to a suitable oral antibiotic regimen. Definite failure at 1 year was 13.6% in the preimplementation group and 18.6% in the postimplementation group (P = .154). Postimplementation, definite failure was more common in patients requiring intravenous antibiotics due to lack of suitable oral options (intravenous, 26.7% and oral, 14.3%). Adverse drug reactions (ADRs) requiring closer monitoring or change to treatment were more common postimplementation (21.0% and 37.1%, respectively). ADR-related hospital readmissions were similar in both groups (2.1 and 2.2%). Comparing both groups, the postimplementation group showed a reduction of 4 days in the median LOS and a median cost reduction of £2764.28 per patient.CONCLUSIONSThe OVIVA trial findings can be safely implemented into clinical practice when patients on oral antibiotics are followed up by an established OPAT service. Two-thirds of patients were switched to a suitable oral antibiotic regimen. Implementation led to reductions in hospital LOS and antibiotic costs.

Introduction Several COVID-19 vaccines against SAR-CoV-2 have demonstrated high efficacy in clinical trials. This is the first report describing their use in a healthcare setting. Methods We conduct a single centre observational study assessing vaccine uptake and apparent efficacy of the Pfizer BioNTech vaccine among healthcare workers (HCW). Results Overall uptake was 60.8%, however we saw statistically significant differences in uptake between age groups, ethnic origins, and job roles. In the 42 days after vaccination, 45 new cases of COVID were identified, of which 4 (8.9%) occurred in HCWs who were beyond 10 days of vaccination. Kaplan Meier curves for vaccinated and unvaccinated groups were congruent until day 14 and continued to diverge up to 42 days. Cox regression analysis showed a 79.0% (95%CI 21 – 95; p=0.02) risk reduction for COVID infection in vaccinated HCWs. Conclusions Initial vaccination rates among HCW were generally good, although uptake was lower in certain groups and efforts should focus on increasing uptake in these groups. The Pfizer BioNTech vaccine is effective from 14 days post-vaccination in a frontline clinical setting and protection continues beyond 21 days post 1st dose without a 2nd dose, being given.

Background: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. Methods: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. Findings: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p=0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. Interpretation: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. Funding: Public Health England. Crown Copyright (C) 2020 Published by Elsevier Ltd on behalf of The British Infection Association. All rights reserved.

We present the first reported case of prosthetic joint infection caused by Trueperella pyogenes. This animal pathogen rarely causes human infection. Our patient was successfully treated with single-stage exchange and 12 weeks of rifampicin and moxifloxacin.

BACKGROUND:There remains no gold standard management for deep shoulder periprosthetic joint infection (PJI). This case series aims to present our experience of two-stage revision arthroplasty, including eradication of infection and reoperation rates.METHODS:We retrospectively reviewed patients undergoing revision arthroplasty for shoulder PJI between 2006 and 2015. Cases were confirmed using Musculoskeletal Infection Society (MSIS) and American Academy of Orthopaedic Surgeons (AAOS) guidelines. TSA removal, debridement and irrigation preceded antibiotic-loaded cement spacer insertion and a minimum of six weeks intravenous antibiotics. Reimplantation was performed as a second stage following a negative aspirate.RESULTS:Twenty-eight patients underwent a first stage procedure (mean age 69 years; 16 male, 12 female). Propionibacterium acnes, Methicillin-sensitive Staphylococcus aureus, Coagulase-negative Staphylococcus and Staphylococcus epidermidis were the commonest microorganisms cultured. Five cases had mixed growths and six cases provided no growth. Three patients did not proceed to a second stage. Twenty-five patients underwent reimplantation (mean interval 6.7 months), with 80% remaining infection-free (mean follow-up 38.3 months).DISCUSSION:Managing complex and late presentation shoulder PJI with two-stage revision is associated with high rates of infection eradication (80%). In the absence of a management consensus, our experience supports two-stage revision arthroplasty for eradicating infection in this complex patient group.

BACKGROUND:The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS:We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS:Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS:Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

We report a case of an infected massive endoprosthetic replacement treated successfully with 2 stage surgery and off-label dalbavancin. Dalbavancin was used due to a limited number of antimicrobial options that could be administered safely in an outpatient setting and to avoid the need for daily dosing.

Background Management of bone and joint infection commonly includes 4–6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. Objective To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. Design Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. Setting Twenty-six NHS hospitals. Participants Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). Interventions Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. Main outcome measure The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. Results Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was –1.38% (90% confidence interval –4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. Limitations The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. Conclusions PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Future work Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. Trial registration Current Controlled Trials ISRCTN91566927. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Abstract Although fungal infections of bones and joints are rare, the increasing incidence of invasive fungal disease, along with an increased population of immunosuppressed patients and individuals with multiple comorbidities, means that these infections are also increasing. The most common organisms are Candida and Aspergillus species, although the endemic dimorphic fungi are responsible for significant numbers of cases in some parts of the world. Most infections occur following haematogenous spread, but invasion from contiguous infection occurs, as does direct inoculation after trauma or surgery. Clinical presentations differ somewhat between children and adults, with the latter more likely to have vertebral osteomyelitis. Clinical presentations may be subtle, often without fever or raised inflammatory markers, and diagnosis may be delayed as a consequence. Diagnosis rests on clinical suspicion coupled with the need to obtain tissue for culture and for histology. Appropriate antifungal therapy usually needs to be prolonged and combined with surgical debridement.

AimDiagnosing Orthopaedic infection is limited by the sensitivity of culture methods. Next generation sequencing (NGS) offers an alternative approach for detection of microorganisms from clinical s...