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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.

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INTRODUCTION: Prosthetic joint infection (PJI) is a rare complication of total knee replacement (TKR), yet it is a serious and debilitating condition. Bacterial infection accounts for the majority of cases and fungal infection is estimated to cause 1% of all prosthesis infection. CASE REPORT: This case presents a 60years female, who presented to our outpatient orthopedic clinic complaining of right knee pain, swelling, and hotness. The physical examination revealed redness, hotness, restricted range of movement, and tibial loosening, 9 months following TKR revision. Culture of the joint aspirate showed growth of "Candida parapsilosis" and second aspirate confirmed the diagnosis. The patient then underwent two stages revision surgery with placement of amphotericin B loaded cement, to maintain high local antifungal concentration in addition to decrease the side effects of amphotericinB infusion such as thrombophlebitis and the more serious systemic effect as nephrotoxicity. The post-operative course was uneventful, with gradual improvement and restoration of normal movement range. CONCLUSION: Fungal PJI is a rare complication of TKR, yet it results in severe debilitating symptoms and impairment of the patient functional capacity. Careful evaluation of the patient followed by a detailed workup is necessary for the identification of the underlying causative micro-organism. Two-stage revision surgery with antifungal loaded cement spacer and antifungal therapy currently is the standard of management. To the best of our knowledge, this is the first fungal PJI following total knee arthroplasty reported in Jordan.

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Fungal periprosthetic joint infections (PJIs) are rare but associated with significant mortality. We report a case of a finger PJI secondary to Aspergillus terreus in an immunocompetent patient with soil exposure, successfully treated with surgical debridement and voriconazole. Identification of A terreus is important because of intrinsic amphotericin B resistance.

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Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo-inorganic sol-gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol-gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol-gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol-gel was sufficient to reduce C. albicans biofilms, and the sol-gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.

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BACKGROUND: Non-albicans Candida prosthetic joint infections (PJIs) are rare. Optimal treatment involves a two-stage revision surgery in combination with an antifungal agent. However, no clear guidelines have been developed regarding the agent or treatment duration. Hence, a broad range of antifungal and surgical treatments have been reported so far. AIM: To clarify treatment of non-albicans Candida PJIs. METHODS: A literature review of all existing non-albicans Candida PJIs cases through April 2018 was conducted. Information was extracted about demographics, comorbidities, responsible species, duration and type of antifungal treatment, type of surgical treatment, time between initial arthroplasty and symptom onset, time between symptom onset and definite diagnosis, outcome of the infection and follow-up. RESULTS: A total of 83 cases, with a mean age of 66.3 years, were located. The causative yeast isolated in most cases was C. parapsilosis (45 cases; 54.2%), followed by C. glabrata (18 cases; 21.7%). The mean Charlson comorbidity index was 4.4 ± 1.5. The mean time from arthropalsty to symptom onset was 27.2 ± 43 mo, while the mean time from symptom onset to culture-confirmed diagnosis was 7.5 ± 12.5 mo. A two stage revision arthroplasty (TSRA), when compared to one stage revision arthroplasty, had a higher success rate (96% vs 73%, P = 0.023). Fluconazole was the preferred antifungal agent (59; 71%), followed by amphotericin B (41; 49.4%). CONCLUSION: The combination of TSRA and administration of prolonged antifungal therapy after initial resection arthroplasty is suggested on the basis of limited data.

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Amphotericin B is used for local delivery from polymethylmethacrylate to treat fungal prosthetic joint infections. The optimal amphotericin B formulation and the influence of different poragens in the bone cements are unknown. To investigate the necessary amount of amphotericin B in the bone cement to prevent Candida biofilm several amphotericin B formulations were studied: non-liposomal and liposomal with or without poragen gentamicin. For the non-liposomal formulation, standard bile salt, the sodium deoxycholate, was used and additionally N-methyl-D-glucamine/palmitate was applied. The activity of the released amphotericin B was tested against C. albicans, C. glabrata, C. parapsilosis and C. krusei biofilms with application of the isothermal calorimeter and standard microbiological methods. Compressive strength was measured before and after antifungal elution from the cements. There is less aggregated N-methyl-D-glucamine/palmitate amphotericin B released but its antifungal activity is equivalent with the deoxycholate amphotericin B. The minimum quantity of antifungal preventing the Candida biofilm formation is 12.5 mg in gram of polymer powder for both non-liposomal formulations. The addition of gentamicin reduced the release of sodium deoxycholate amphotericin B. Gentamicin can be added to N-methyl-D-glucamine/palmitate amphotericin B in order to boost the antifungal release. When using liposomal amphotericin B more drug is released. All amphotericin B formulations were active against Candida biofilms. Although compressive strength slightly decreased, the obtained values were above the level of strength recommended for the implant fixation. The finding of this work might be beneficial for the treatment of the prosthetic joint infections caused by Candida spp.

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Anfotericina B/análogos & derivados , Anfotericina B/farmacología , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Ácido Desoxicólico/farmacología , Anfotericina B/química , Antifúngicos/química , Biopelículas/crecimiento & desarrollo , Cementos para Huesos/análisis , Cementos para Huesos/química , Candida albicans/crecimiento & desarrollo , Candida glabrata/efectos de los fármacos , Candida glabrata/crecimiento & desarrollo , Candida parapsilosis/efectos de los fármacos , Candida parapsilosis/crecimiento & desarrollo , Fuerza Compresiva , Ácido Desoxicólico/química , Combinación de Medicamentos , Liberación de Fármacos , Gentamicinas/farmacología , Cinética , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Polimetil Metacrilato/análisis , Polimetil Metacrilato/química , Porosidad

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Fungal periprosthetic joint infections due to Aspergillus species are rare but are associated with significant cost and morbidity. We present a case of Asperigillus terreus prosthetic joint infection of the hip. The patient was successfully treated with a prolonged course of systemic antifungals along with surgical management.