Aims. Fungal periprosthetic joint infections (fPJIs) are rare complications, constituting only 1% of all PJIs. Neither a uniform definition for fPJI has been established, nor a standardized treatment regimen. Compared to bacterial PJI, there is little evidence for fPJI in the literature with divergent results. Hence, we implemented a novel treatment algorithm based on three-stage revision arthroplasty, with local and systemic antifungal therapy to optimize treatment for fPJI. Methods. From 2015 to 2018, a total of 18 patients with fPJI were included in a prospective, single-centre study (DKRS-ID 00020409). The diagnosis of PJI is based on the European Bone and Joint Infection Society definition of periprosthetic joint infections. The baseline parameters (age, sex, and BMI) and additional data (previous surgeries, pathogen spectrum, and Charlson Comorbidity Index) were recorded. A therapy protocol with three-stage revision, including a scheduled spacer exchange, was implemented. Systemic antifungal medication was administered throughout the entire treatment period and continued for six months after reimplantation. A minimum follow-up of 24 months was defined. Results. Eradication of infection was achieved in 16 out of 18 patients (88.8%), with a mean follow-up of 35 months (25 to 54). Mixed bacterial and fungal infections were present in seven cases (39%). The interval period, defined as the period of time from explantation to reimplantation, was 119 days (55 to 202). In five patients, a salvage procedure was performed (three cementless modular knee arthrodesis, and two Girdlestone procedures). Conclusion. Therapy for fPJI is complex, with low cure rates according to the literature. No uniform treatment recommendations presently exist for fPJI. Three-stage revision arthroplasty with prolonged systemic antifungal therapy showed promising results. Cite this article: Bone Jt Open 2021;2(8):671–678

Abstract. Aims. 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. Patients and Methods. 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). Results. The mean age at presentation was 69 years (range 46 to 87) and mean BMI was 31 kg/m2 (range 20 to 44). The median number of procedures that patients had on the affected limb from the index primary arthroplasty procedure was 6 (range 2–17). The median procedure number at which a fungal infection was identified was 5 (range 2–10). A history of prolonged antibiotic therapy (above 6 months total) was present in 37 patients (88%). During the study period 22 patients were infection free, 14 treated with lifelong suppression, 7 had above knee amputations and 6 had died. Overall infection cure rate was 49%. Conclusions. Patients with fungal PJI are generally poor hosts with multiple co-morbidities, long term exposure to antibiotics and high rates of open wounds and sinuses. The poor outcome associated with fungal PJI relative to bacterial PJI should be shared with patients in order to manage the expectations of this complex cohort

Introduction

Fungi are a rare and devastating cause of Periprosthetic Joint Infection (PJI). Diagnosis and treatment is a challenge as there are currently no specific guidelines. A recently published review identified 75 case reports of fungal PJI.

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

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

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