INTRODUCTION. Peri-prosthetic fungal infection is generally considered more difficult to cure than a bacterial infection. Two-stage exchange is considered the gold standard of surgical treatment. A recent study, however, reported a favorable outcome after one stage exchange in selected cases where the fungus was identified prior to surgery. The routine one stage exchange policy for bacterial peri-prosthetic infection involves the risk of identifying a fungal infection mimicking bacterial infection solely on intraoperative samples, i.e. after reimplantation, realizing actually a one stage exchange for fungal infection without pre-operative identification of the responsible fungus, which is considered to have a poor prognosis. We report two such cases of prosthetic hip and knee fungal infection. Despite this negative characteristic, no recurrence of the fungal infection was observed. CASE N°1: A 78 year old patient was referred for loosening of a chronically infected total hip arthroplasty (Staphylococcus aureus and Streptococcus dysgalactiae). One stage exchange was performed. Intraoperative bacterial cultures remained sterile. Two fungal cultures were positive for Candida albicans. Antifungal treatment was initiated for three months. No infection recurrence was observed at three year follow up. CASE N° 2: A 53-year-old patient was referred for loosening of a chronically infected total knee prosthesis (Staphylococcus aureus methicillin susceptible, Klebsiella pneumoniae and Staphylococcus epidermidis). One stage exchange was performed. Intraoperative bacterial cultures remained sterile. Five fungal cultures were positive for Candida albicans. Antifungal treatment was initiated for three months. No infection recurrence was observed at two-year follow-up. DISCUSSION. This experience suggests that eradication of fungal infection of a total hip or knee arthroplasty may be possible after one stage exchange even in cases where the diagnosis of fungal infection was not known before surgery, when the fungus was not identified and its antifungal susceptibility has not been evaluated before surgery. It is however not possible to propose this strategy as a routine procedure. CONCLUSION. We suggest evaluating the results of one stage exchange for peri-prosthetic fungal infection on a larger scale

Aim. Fungal orthopaedic infections most commonly affect people with complex surgical histories and existing comorbidities. Recurrence and re-infection rates are high, even with optimal surgical and systemic antifungal treatment. AmBisome liposomal amphotericin B has been suggested for local antifungal therapy, as an adjunctive treatment for fungal osteoarticular infections. Few case series have examined its clinical use when combined with polymethylmethacrylate cement PMMA), or with absorbable local antibiotic carriers. We aimed to evaluate the clinical use of local antifungal therapy with AmBisome liposomal amphotericin B (ABlaB), including tolerated doses, serious adverse events, and treatment outcomes. Method. A retrospective cohort of all patients treated with local antifungal therapy with ABlaB between January 2016 and January 2021 in a specialist orthopaedic hospital was identified using pharmacy records. Renal function, serious adverse events during treatment, surgical outcomes including spacer fracture and infection recurrence, were identified from electronic clinical records. The project was approved by the Institutional Review Board (clinical audit 6871). Results. 13 operations involving local antifungal therapy with ABlaB, in 12 patients, were identified. Eleven were infected with Candida species and one with Aspergillus. Mean follow-up was 22 months (range 4–46). Ten first stage arthroplasty revisions, 2 second stage arthroplasty revisions, and one debridement and removal of metalwork for fracture-related infection were performed. Locally implanted doses of ABlaB ranged from 100mg to 3600mg (50–400mg per 40g mix of PMMA). Six patients received ABlaB in absorbable antibiotic carriers containing calcium sulphate. This was noted to delay carrier setting. Patients were also given systemic antifungal therapy. No patients experienced serious adverse events related to toxicity from local antifungal therapy with ABlaB. There were no spacer fractures. Overall treatment success was 54% at final follow-up, although there were no recurrent fungal infections identified in patients experiencing treatment failure. Conclusions. Local antifungal therapy with liposomal amphotericin B, when combined with surgery and systemic therapy, appears to be a safe and well tolerated intervention in the management of complex fungal osteoarticular infections

Aim. Fungal periprosthetic joint infections are difficult to treat and often associated with a limited outcome for patients. Candida species account for approximately 90% of all fungal infections. In vivo biofilm models play major role to study biofilm development, morphology, and regulatory molecules for bacteria. However, in vivo modeling of biofilm-associated fungi models are very rare. Furthermore, due to ethical restrictions, mammalian models are replaced with other alternative models in basic research. Recently, we have developed insect infection model G. mellonella larvae to study implant associated biofilm infections with bacteria. This model organism was not used for fungi biofilm infection yet. Thus, we aimed to establish G. mellonella as in vivo model to study fungal implant infections using Candida albicans as model organism and to test anti-fungal medication. Method. Titanium and Stainless steel K-wires were cut into small pieces with size of 4mm. For the infection process, implants were pre-incubated in specified fungal growth culture Candida albicans at 1×10. 7. CFU/ml for 30 min at 150 rpm shaking conditions. Later, these implants were washed with 10ml PBS and implanted in the larvae as mentioned. To analyze the susceptibility of the implant-associated fungal infections towards anti fungal compounds, the larvae were treated with amphotericin B, fluconazole and voriconazole after 24h of implantation. The effect of anti-fungal compounds was measured in terms of survival observation for 5 days and fungal load in larvae on 2. nd. day. To reveal the fungal biofilm formation on implant, the implants were removed on day 3 and processed for SEM analysis. Results. Pre-incubated K-wire caused the Candida infection and observed the death of the larvae. The treatment with antifungal compounds recovered the larvae from the implant-infection, except in case of Voriconazole. However, the recovery with treatment of anti fungal compounds was not effective as the larvae with planktonic infection, which highlights typical biofilm phenotype. Further, the treatment with anti-fungal compounds with Amphotericin B and Fluconazole reduced the fungal load in larvae tissue. The SEM analysis revealed the formation fungal biofilm with hyphae and spores associated with larvae tissue on implant surface. Conclusions. The results from survival analysis, antifungal treatment and SEM analysis are very promising to use of G. mellonella as in vivo model to study fungal infections on implanted materials. Our study highlights the use of G. mellonella larvae as alternative in vivo model to study implant-associated fungal infections that reduces the use of the higher mammals

Aims. Periprosthetic fungal infections are rare and account for 1–2% of all periprosthetic joint infections (PJI). This study aims at presenting treatment details, clinical and microbiological results in a large single centre cohort. Methods. We retrospectively identified 29 patients (9 total knee replacements (TKA) and 20 total hip replacements (THA) treated for a fungal infection between 2007 and 2019. Microbiological findings, patient demographics and complications were analysed. Statistical analysis was performed using descriptive statistics; non-parametric analysis were performed using the Mann-Whitney U-Test. Infection-free survival was determined using Kaplan-Meier analysis and differences in survival were analysed using the log-rank test. The p value was set at p<0.05 with 95% confidence intervals (95% CI) provided. Results. 28% (8/29) suffered from reinfection. The reinfection-free survival probability was 65% (95% CI 45–85) after a median follow- up period of 28 months (IQR 6 – 39). With the numbers we had, we were not able to detect a difference between THA and TKA re-infections (p=0.517). Four patients underwent amputation, 3 patients had a definitive girdlestone hip and eight patients died after a median of 5 months after first-stage surgery (IQR 1–7). All patients treated had positive synovial fluid or tissue cultures for Candida species. In 22 /29 patients C. albicans, in 3 patients C. parapsilosis, in 2 patients C. glabrata and in 1 patient each C. famata, C. dubliniensis and C. gulliermondii. Polymicrobial bacterial infection was found in 86% of patients with staphylococci in 20 patients, E. coli in 2 patients, vancomycin-resistant enterococci, pseudomonas, acinetobacter and achromobacter species in 1 patient each. When investigating risk factors for reinfection, with the numbers we had we were not able to find a significant difference for patients with polymicrobial infection (p=0.974), azole-resistant Candida (p=0.491), tobacco users (p=0.175), or diabetics (p=0.54). Furthermore, median age (73 vs. 72, p=0.756) and Charlson comorbidity score (6 (interquartile range (IQR) 4–8) vs. 8 (IQR 5–10), p=0.184) were not different between the groups while on the other hand there was a trend for a higher body mass index in patients with reinfection (34 (IQR 31–38) vs. 28 (IQR 25–33), p=0.075). Conclusions. Fungal PJI is associated with poor reinfection free survival, frequent revisions, and high mortality. All infections were caused by Candida spp. in which azole-resistance most be considered when planning treatment. While polymicrobial infection complicated treatment there was no difference in survival. A higher BMI and comorbidity score might be associated with higher risk for reinfections

Aim. Sepsis is a life-threatening complication of periprosthetic joint infections (PJI) that requires early and effective therapy. This study aims to investigate the epidemiology, associated risk factors, and outcome of sepsis in the context of periprosthetic joint infections (PJI). Method. This single-center retrospective cohort study included patients treated for PJI from 2017 to 2020. Patients were classified based on the criteria of the European Bone and Joint Infection Society. The presence of sepsis was determined using the SOFA score and SIRS criteria. The cohort with PJI and sepsis (sepsis) was compared to patients with PJI without sepsis (non-sepsis). Risk factors considered were patient characteristics, affected joints, surgical therapy, microbiological findings, preexisting medical conditions, clinical symptoms, and symptom duration. Outcome parameters were mortality, length of hospital stay, and length of stay in the intensive care unit. Results. A total of 109 patients with PJI were identified, of whom 45 patients (41.3%) met the criteria for sepsis. Patients with sepsis had more severe preexisting diseases compared with the non-sepsis cohort (Charlson Comorbidity Index 3.8 vs. 2.8; p≤0.001). An increased odds ratio (OR) for a septic course was found for the comorbidities pneumonia (8.2; p=0.001), myocardial infarction (2.0; p=0.02), atrial fibrillation (3.3; p=0.01), diabetes mellitus (1.2; p=0.04), endocarditis (5.5; p=0.01), and renal disease (2.0; p≤0.001). Infection with Staphylococcus aureus (sepsis 20 vs. non-sepsis 10; p=0.002), Streptococcus dysgalactiae (sepsis 7 vs. non-sepsis 2; p=0.002) and Candida albicans (sepsis 5 vs. non-sepsis 0; p=0.01) were more prevalent in patients with sepsis. In the sepsis cohort, further infectious foci were present in addition to PJI in 57.8% of patients, compared to 18.8% in the non-sepsis cohort. The presence of sepsis was associated with a longer hospital stay (sepsis 68 days vs. non-sepsis 38 days; p=0.001) and longer intensive care unit stay (sepsis 12 days vs. non-sepsis 2 days; p=0.001). In-hospital mortality was ten times higher in the sepsis cohort compared to non-septic patients (sepsis 11/42 vs. non-sepsis 2/64; OR 10.3; p=0.01). Conclusions. In a relevant proportion of patients, PJI can lead to a septic course of disease associated with increased mortality. Particularly in patients with preexisting diseases, increased attention is required, and comprehensive screening for other foci of infection seems mandatory. In addition to highly virulent pathogens such as staphylococci and streptococci, fungal infections should be considered as causative pathogens in septic patients with PJI

Periprosthetic joint infections are one of the most dreaded and complex complications of total joint arthroplasty, with fungal infection accountting for less than 1% of the cases. Treatment is challenging due to the lack of scientific evidence. We report a case of a Candida albicans total hip arthroplasty (THA) infection and performed a review of the literature. We report a case of a 79 year old women with an early THA infection (less of one month) from the primary surgery. She presented with pain and serous drainage from the operative wound and for that was submited to surgical debridement and revision of polyethilene. Cultures where taken (steril) and empirical vancomicin and rifampicin treatment was initiated. Because of persistent complains and drainage, the patient was submitted to another surgery. Cultures were taken at the time of surgery. A cement spacer impregnated with gentamicin was placed after implant removal. Cultures isolated Candida albicans. In light of this new evidence fluconazole was added to the previous scheme. After introduction of fluconazole, the clinical evolution was good. Drainage stoped 1 week after, and the wound closed. The inflammatory markers became normal shortly after. Leg pain became better. The patient was given oral suppressive treatment with fluconazole and was discharged, weight bearing as tolerated. A total of 4 mouths of treatment is programmed with close follow-up, untill the second staged revision is programmed. Prosthetic fungal infections are rare with most of the published articles being case reports. A substantial delay in diagnosis may occur because culture results are sometimes interpreted as contamination and there is a need for obtaining multiple samples, prolonged culture, and special staining. The best results are being reported with a long period of oral antifungal treatment and a two staged joint revision but there is an absence of standardized clinical and evidence-based treatment guidelines

We report the clinical features and treatment on a rare case of Candida albicans lumbar spondylodiscitis in a non-immunocompromised patient. Its indolent course leads to delayed suspicion and diagnosis. As soon as fungal infection is suspected investigations with MRI and biopsy should be performed followed by medical therapy. Retrospective data analysis. A 58-year-old male underwent surgery for adenocarcinoma of the ampula of Vater treatment. Subsequently, the patient had a prolonged intensive care unit stay due to major complications, during his stay he developed a septicemia with Candida albicans isolated in the blood work. He received antifungal therapy anidulofungin, later changed to fluconazole during 2 weeks. Repeated blood work were negative and no vegetations on echocardiogram were seen. He was discharged from the ICU to a surgery floor. During the surgical unit stay he presented with lower back pain radiating to the lower limbs. Findings on neurological examination were normal, radiographs of the lumbar spine revealed L5-S1 antero listhesis. He was treated with oral non-steroidal anti-inflammatory drugs and an lumbar MRI and orthopaedic consultation was agended. One month later, after minor trauma he developed myelopathic symptoms with weakness of both lower limbs and severe back pain. Plain radiograph showed anterolistesis worsening. Magnetic resonance imaging showed endplate erosion at L5/S1. There also was evidence of paraspinal collection with epidural compression of the dural sac. The patient was treated surgicaly with debridement and posterior instrumented fusion from L4 to S1. Disk and end-plate material collected confirmed Candidal infection. The patient recovered most of his neurological deficit immediately after surgery. He was subsequently treated during 2 weeks with liposomal amphotericin B, later changed to fluconazole 400mg per os per day. He maintained antifungal therapy during 15 months. He remains asymptomatic with no recurrence of infection clinically or radiologically after surgery. Fungal spondylodiscitis is rare. Sub-acute or chronic low back pain in either immunocompromised or non-immunocompromised patients cronically ill and malnourished (parental nutrition) there must be high index of suspicion for fungal infections. Therefore we recommend screening for Candida osteomyelistis in these cases. Without treatment, involvement of vertebral bodies can lead to compression fractures, deformity of the spine and neurological impairment

Deep peri-prosthetic infection after partial or total knee arthroplasty is a disconcerting problem for patient and surgeon alike. The diagnosis of infection is sometimes obvious but frequently requires that the surgeon maintain a substantial index of suspicion for infection as the cause of pain or poor outcome after any joint arthroplasty. While surgical debridement with component retention is appropriate in a subgroup of patients with an acute peri-prosthetic infection, most delayed and chronic infections are best treated with component resection. With carefully selected patients and very aggressive debridement protocols some success has been demonstrated in Europe with single-stage exchange for infection. Most surgeons in North America, however, are unfamiliar with the very aggressive debridement techniques employed at European centers that promote single stage replant; and few surgeons in North America are currently comfortable in cementing a hinged total knee replacement in place for the typical infected TKA nor do they have the patience to re-prep and drape with an entirely new OR setup after debridement and prior to the insertion of the new implant − 2 steps that are often mentioned as important to the success of single stage exchange. The pre-eminent role of two-stage exchange as the definitive treatment was established over 30 years ago. Two-stage exchange remains the gold-standard in treatment with an established track record from multiple centers and with multiple different types of infecting organisms. Some of the historical problems with two-stage exchange, such as limited mobility during the interval stage, have been mitigated with the development of effective articulating spacer techniques. Further, the emergence of drug resistant bacteria and the possibility of fungal infection make two-stage exchange the best choice for the majority of patients with deep periprosthetic joint infection in 2017

Purpose. Management and outcomes of fungal periprosthetic joint infection (PJI) remain unclear due to its rarity. Although two-stage exchange arthroplasty is considered a treatment of choice for its chronic features, there is no consensus for local use of antifungal agent at the 1st stage surgery. The purpose of this study was to evaluate the efficacy of antifungal-impregnated cement spacer in two-stage exchange arthroplasty against chronic fungal PJIs after total knee arthroplasty (TKA). Methods. Nine patients who were diagnosed and treated for chronic fungal PJIs after TKA in a single center from January 2001 to December 2016 were enrolled. Two-stage exchange arthroplasty was performed. During the 1st stage resection arthroplasty, amphotericin-impregnated cement spacer was inserted for all patients. Systemic antifungal medication was used during the interval between two stage operations. Patients were followed up for more than 2 years after exchange arthroplasty and their medical records were reviewed. Results. The average duration from the initial symptom to fungal PJI diagnosis was 20 months (range, 5 to 72 months). Average erythrocyte sedimentation rate and C-reactive protein level at diagnosis were 56 mm/h (range, 30 to 89 mm/h) and 2.25 mg/dl (range, 0.11 to 3.97 mg/dl), respectively. Fungal PJI was confirmed by preoperative joint aspiration culture in 6 cases. For the other 3 cases, it was confirmed by open debridement tissue culture. All infections were caused by Candida parapsilosis except for one case which was caused by Candida pelliculosa. The average number of operations before exchange arthroplasty to solve the infection was 2.7 times (range, 1 to 5 times). Average duration of antifungal agent use confirmed by sensitivity test was 7 months (range, 4 to 15 months). Mean interval between two stage operation was 6 months (range, 1.5 to 15 months). After two-stage exchange arthroplasty, no patient had recurrent fungal infection during a mean follow-up of 66 months (range, 24 to 144 months). Conclusions. Due to its ill-defined symptoms and inconclusive blood test, fungal PJI after TKA is difficult to diagnose and has a prolonged clinical course. Two-stage exchange arthroplasty with antifungal-impregnated cement spacer is a very effective strategy with excellent outcome

Deep periprosthetic infection after hip or knee arthroplasty is a disconcerting problem for patient and surgeon alike. The diagnosis of infection is sometimes obvious but frequently requires that the surgeon maintain a substantial index of suspicion for infection as the cause of pain or poor outcome after any joint arthroplasty. While surgical debridement with component retention is appropriate in a subgroup of patients with an acute periprosthetic infection most delayed and chronic infections are best treated with component resection. The pre-eminent role of two-stage exchange as the definitive treatment was established over 30 years ago. Two-stage exchange remains the gold-standard in treatment with an established track record from multiple centers and with multiple different types of infecting organisms. Some of the historical problems with two-stage exchange, such as limited mobility during the interval stage, have been mitigated with the development of effective articulating spacer techniques. Further, the emergence of drug resistant bacteria and the possibility of fungal infection make two-stage exchange the best choice for the majority of patients with deep periprosthetic joint infection in 2015

Skeletal Cryptococcosis although rare has been reported in immunodeficient individuals and in particular those with HIV. We present a case in a HIV- negative patient who presented to the London Sarcoma service masquerading as a primary bone tumour and review the relevant literature. A 71 year old lady presented with a three month history of right submammary pain associated with a new lump. Chest radiographs showed an osteolytic lesion in the right 6. th. rib. CT scans demonstrated mediastinal lymphadenopathy and numerous lung nodules. Differential diagnosis of the lesion included TB abscess, myeloma, lymphoma or as a primary lung tumour presenting with hilar lymphadenopathy and necrotic skeletal metastasis. CT guided biopsy was performed with histology showing necrotising granulomatous inflammation with numerous yeast like organisms in keeping with Cryptococcus fungal infection. She was treated successfully with a six week course of voriconazole. Cryptococcal skeletal infections can cause significant morbidity and mortality and should be considered as a rare cause of lytic osseous lesions

Background. Fungal infection at an arthroplasty site is rare and poses a therapeutic challenge. To the best of our knowledge, no reports have been published thus far on the success rate of prosthesis reimplantation after fungal prosthetic joint infections. Questions/purposes. We asked: (1) What is the success rate in terms of infection eradication using a two-stage exchange arthroplasty in patients with hip or knee fungal periprosthetic joint infections, particularly focusing on Candida infections? (2) What patient-, infection-, and treatment-related variables are associated with the success or failure of treatment?. Methods. From January 2000 to December 2010, 16 patients with hip or knee candidal periprosthetic joint infections were treated with two-stage exchange arthroplasty at our institute. Treatment success was defined as a well-functioning joint without relapse of candidal infection after prosthesis reimplantation, while treatment failure was defined as uncontrolled or a relapse of candidal infection or mortality. Variables, including age, sex, comorbidities, microbiology, antimicrobial agents used, and operative methods, were analyzed. Minimum followup was 28 months (mean, 41 months; range, 28–90 months). Results. At latest followup, the treatment failed to eradicate the infection in eight of the 16 patients, and there were four deaths related to fungemia. Four patients required permanent resection arthroplasty owing to uncontrolled or recurrent candidal infections. All eight patients (50% successful rate) who had their infections eradicated and successful prosthesis reimplantation had prolonged treatment with oral fluconazole before (mean, 8 months) and after (mean, 2.2 months) prosthesis reimplantation. The antifungal therapy correlated with successful treatment. Renal insufficiency, hypoalbuminemia, anemia, and chronic obstructive pulmonary disease were significantly more prevalent in the treatment-failure group than in the treatment-success group. Conclusions. Half of the patients treated with two-stage exchange arthroplasty for fungal periprosthetic joint infections had recurrence or lack of control of the infection. A prolonged antifungal therapy appeared to be essential for successful treatment of candidal periprosthetic joint infections. The presence of renal insufficiency, hypoalbuminemia, anemia, or chronic obstructive pulmonary disease might be associated with a poor outcome

Background. Chronic osteomyelitis with intramedullary sequestrum resulting in persistent infection is a challenging orthopaedic problem that often involves multiple surgical operations and unfortunately has a significant recurrence rate. Reasons for this may include difficulty in eradicating all intramedullary microsequestra making subsequent prolonged antibiotic therapy less effective. Use of the Reamer-Irrigator-Aspirator (RIA) has many advantages for management of intramedullary infections in chronic osteomyelitis. The RIA technique allows irrigation of sterile large quantities of saline with simultaneous bony debridement with very sharp reamers that are specially designed to allow simultaneous fluid aspiration. Purpose. We will illustrate the pearls and pitfalls associated with the RIA technique, based on our experience so far. Method. We retrospectively reviewed a number of 6 (six) patients with chronic osteomyelitis of tibia (n=2) and femur (n=4). In an average follow up of 9.6 months post treatment (range 3–18 months) using a protocol including treatment with RIA we noticed immediate control of infection. Complications. Include pin tract infection, pin site pain and fungal infection (due to prolonged use of antibiotics). Conclusion. Based on our patient series so far, the encouraging results we have seen with regard to eradication of infection lead us to believe that RIA has a valuable role to play in the treatment of chronic osteomyelitis

Aims

Diabetes mellitus is the most common co-morbidity associated with necrotising fasciitis. This study aims to compare the clinical presentation, investigations, Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score, microbiology and outcome of management of this condition in diabetic and non-diabetic patients.