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

The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. We thank H.Y. Hsu for performing the bioassay

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

Objectives. This study is to compare the elution characteristics, antimicrobial activity, and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powder antibiotic, powder antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder, and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin–loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or xylitol group. Regarding the amphotericin B–loaded ALBCs, only the eluate samples of the liquid group exhibited a clear inhibitory zone which was not observed in either xylitol nor powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the antibiotic-release efficacy than that by loading ALBC with the same dose of antibiotic powder. This simple, and effective method for preparation of ALBCs can significantly improve the antibiotic-release efficacy of ALBCs

Aim. Optimal strategies for surgical and antimicrobial management of Candida periprosthetic joint infections (PJI) are unclear. We present a retrospective case series of patients diagnosed with PJI caused by Candida spp. Method. Patients treated at our institution with Candida PJI from 01/2017 to 04/2018 were retrospectively included with isolation of Candida spp. in synovial fluid, intraoperative tissue or sonication fluid culture. PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Treatment failure was defined as relapse or persistence of infection. Results. We included 9 patients (4 men and 5 women, mean age 75 years) involving 4 knee and 5 hip joint prosthesis. Risk factors for Candida PJI were prior PJI (n=4), diabetes mellitus (n=3), chronic kidney disease (n=3), obesity (n=3), negative-pressure wound therapy (n=3), rheumatoid arthritis (n=1) and chronic decubitus (n=1). Two patients had no risk factors for Candida PJI identified. Infection was acquired postoperatively (n=7), hematogenously (n=1) or contiguously through communicating vesico-articular sinus (n=1). The causative pathogen was C. albicans in 5, C. parapsilosis in 3, C. tropicalis in 1 patient, isolated from periprosthetic tissue samples (n=7), sonication fluid (n=3) and blood cultures (n=2); bacterial co-pathogens were isolated in 8 patients. Histopathological analysis revealed low-grade inflammation in all 6 patients, in whom it was performed. All patients were treated with oral fluconazole for 3 months, two initially received intravenous caspofungin and three received suppression with oral fluconazole for additional 9 months (total treatment 12 months). Liposomal amphotericin B (300–700 mg per 40 g bone cement) was admixed to spacer cement in 3 patients. Debridement and prosthesis retention was performed in one patient with tumor prosthesis after bone resection due to osteochondrosarcoma. In the remaining 8 patients the prosthesis was removed, with one-stage reimplantation in 1 patient and two-stage reimplantation in 3 patients (after 6 weeks, 3 months and 7 months); two patients are currently awaiting reimplantation, one died due to reason not related to PJI and another underwent knee arthrodesis. Among 5 patients with prosthesis in place, relapse occurred in one patient with prosthesis retention. Another patient experienced new PJI of the exchanged prosthesis caused by Staphylococcus aureus. Conclusions. All Candida PJI presented as chronic infection with low-grade inflammation. Treatment with prostheses retention failed, whereas in 4 patients who underwent two-stage exchange and long-term antifungal suppression, no relapse or persistence of infection was observed. All patients received oral fluconazole for ≥3 months

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

Diagnosis, treatment and outcome in systemic infection caused by Coccidioides Immitis in a non endemic region. First case in Spain. 71 year old patient. Symptoms: stomach aches, tiredness and weight loss of 14kg. Imaging Investigations: Abdominal pelvic US and Gastroscopy were performed as cancer was suspected. This study showed a bilateral suprarrenal mass. Fearing a pulmonary mass a Thoracic Scan was requested. Results proved mediastinal and axillary nodes. Also found was interstitial illness which lead to a working diagnosis of Granulomatous Lymphangitis. BIOPSIES: An axillary lymph node, suprarrenal gland and pulmonary tissues. ANATOMOPATHOLOGY: Necrotising Granulomatous Lymphadenitis. DIFFERENTIAL DIAGNOSIS: TBC, Sarcoidosis and Autoinmune illnesses. SAMPLE CULTURES were repeatedly negative for funghi, bacteria and Mycobacterium. DIAGNOSIS The patient was subsequently he was commenced on Substitute Hormonal Therapy with improvement of symptoms. MANAGEMENT: Due to a gonarthrosis he required Total Knee Arthroplastia. During surgery a prominent SINOVITIS was noticed, with anatomopathology results of Chronic Necrotising Granulomatous Sinovitis with lymphoid folicules. FOLLOW UP: 7 years after the patient attends A&E with signs of infection on the replaced knee. A bacterial infection is suspected and the patient is admitted into hospital for the replacement extraction, cement substitution with Gentamicin and iv antibiotherapy with LEVOFLOXACIN. His symptoms improved up to a month when he returned to A&E with similar presentation THE PATIENT IS ADMITTED ONCE MORE FOR SURGERY:. Sample Cultures from the prosthesis showed positive growth for Coccidiodes Immitis. Article Reviews provided us with brand new information. A new approach was taken and anamnesis was geared towards finding out a possible contact with the funghi in the endemic region. It appeared that the patient had worked as a Shepherd for four years (1957–1961) in Bakersfield. A Southern Californian region north to LA and under San Francisco. After all, he was admitted for 25 days in a local hospital for pneumonia. DIAGNOSIS WAS REACHED thanks to these findings. The old spacer wasswapped for a Cement Spacer with Amphotericin B 250 mg. Oral treatment with FLUCONAZOL 400 mg/day was associated and after a few days changed to ITRACONAZOL 200 mg/12 hours orally. The patient improved local and systemically. After a few months he evolved as planned and now has a good general and local condition with normal biochemistry results. A final ARTHRODESIS was performed. It's quite likely that he may require long life therapy with Antifungals to avoid reactivations. We highlight the originality of the case, as the first diagnosis of articular Coccidioides diagnosed in Spain, and its successful outcome with prosthetic replacement rebound and chronic antifungal therapy