Analysis of epidemiological and clinical aspects in cases of fungal osteomyelitis caused by non-Candida species.

Osteomyelitis caused by non-Candida species is rare and often neglected, and current recommendations are based on primarily clinical experience and expert opinion. The objective of this study was to describe a case series of non-Candida fungal osteomyelitis. This retrospective study included 10 patients with non-Candida fungal osteomyelitis. Patients with osteomyelitis and microbiologically confirmed non-Candida species from bone fragment cultures were selected from the institution Infection Control Board database. Fusarium spp. were the most commonly isolated fungus from bone fragment cultures in five patients (50%). The majority did not present immunosuppression. The most common etiology was post-traumatic (n = 7, 70%), particularly open fractures. All patients were treated with antifungals associated with surgery. The antifungals used were itraconazole in five patients (50%), and voriconazole in another five patients (50%), with a median duration of antifungal therapy of four weeks (range: 3-25). There were no observed deaths within 30 days and one year. An antifungal approach combined with surgical treatment demonstrated favorable clinical outcomes, including low mortality rates and effective remission.

Coccidioidomycosis Osteoarticular Dissemination.

Valley fever or coccidioidomycosis is a pulmonary infection caused by species of Coccidioides fungi that are endemic to California and Arizona. Skeletal coccidioidomycosis accounts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues, causing significant pain and restricting mobility. Manifestations of such cases are usually nonspecific, making diagnosis very challenging, especially in non-endemic areas. The lack of basic knowledge and research data on the mechanisms defining susceptibility to extrapulmonary infection, especially when it involves bones and joints, prompted us to survey available clinical and animal data to establish specific research questions that remain to be investigated. In this review, we explore published literature reviews, case reports, and case series on the dissemination of coccidioidomycosis to bones and/or joints. We highlight key differential features with other conditions and opportunities for mechanistic and basic research studies that can help develop novel diagnostic, prognostic, and treatment strategies.

Fungal Osteomyelitis: A Systematic Review of Reported Cases.

Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was Aspergillus (26.5%), followed by Candida (20.7%) and Mucor (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.

Osteomyelitis caused by Aspergillus terreus complex in a dog: a case report.

BACKGROUND: In dogs, the most frequently reported mycosis associated with Aspergillus spp. are respiratory infections. Systemic aspergillosis is uncommon, with reported cases been associated with several Aspergillus species. Aspergillus terreus species complex are ubiquitous organisms, unfrequently associated with local or systemic disease in animals and humans, and treatment of osteomyelitis caused by this species is usually unfavorable. CASE PRESENTATION: This case report describes the case of a 5-year-old dog, referred to the Veterinary Hospital of the Faculty of Veterinary Medicine of the University of Lisbon, Portugal, with a history of lameness of the right thoracic limb. Radiographs and CT scan revealed two different lesions on right humerus and radio, which were biopsied. The samples collected were submitted to cytological and histopathological evaluation and bacterial and mycological culture. Environmental samples, including of the surgery room and of the biopsy needle were also evaluated for the presence of fungi. Regarding biopsy samples, bacterial culture was negative, but mycological analysis originated a pure culture of a fungal species later identified as Aspergillus terreus by Sanger sequencing. Results were compatible with histopathologic examination, which revealed periosteal reaction and invasion of hyphae elements. Also, mycological analysis of both environmental samples evaluated were negative. The virulence profile of the fungal isolate was phenotypically characterized using specific media, allowing to reveal its ability to produce several enzymes involved in its pathogenicity, namely lipase, hemolysin and DNAse, corresponding to a Virulence Index (V. Index.) of 0.43. The patient was submitted to itraconazole therapy for 8 weeks. After 3 weeks, the patient showed significant clinical improvement, and after 6 weeks no radiographic signs were observed. CONCLUSIONS: Antifungal therapy with itraconazole can contribute to the remission of canine infections promoted by Aspergillus terreus complex with a relevant V. Index.

The Utility of Acid-Fast Bacillus (AFB) and Fungal Cultures in Orthopaedic Infections.

Introduction When diagnosing suspected orthopaedic-related infections, fungal and acid-fast bacilli (AFB) cultures are often obtained intraoperatively. These cultures are difficult and time-consuming to grow and increase healthcare costs. This study aimed to quantify the rate of positive AFB and fungal cultures in orthopaedic infections and to compare potential risk factors for a positive result.  Methods Orthopaedic surgical cases for suspected infection at one institution from March 2013 through December 2019 were included. Data were collected on patient demographics and procedure characteristics for patients with surgical AFB or fungal lab tests ordered on the day of surgery. Results Of the 813 patients for whom intraoperative AFB or fungal cultures were ordered, 3.8% (N=31) had a positive result. Of the 31 positive results, 30 were from fungal cultures and one was from AFB cultures. Patients with a positive versus negative culture result did not differ significantly by age, sex, American Society of Anesthesiologists (ASA) score, diabetes, obesity, or HIV/AIDS. In both unadjusted and adjusted analyses, peripheral vascular disease (PVD) was associated with higher odds of a positive fungal culture result (adjusted OR (aOR)=3.5, 95%CI=1.3-8.4). Likewise, in both unadjusted and adjusted models, a hand/foot operating region was associated with higher odds of a positive fungal culture result compared with all other regions (aOR=4.2, 95%CI=1.9-9.8). Conclusion Intraoperative fungal and AFB cultures may not need to be obtained except in orthopaedic surgical cases for hand or foot infections or in patients with PVD.

A Rare Case of Candida parapsilosis Lumbar Discitis With Osteomyelitis.

Fungal osteomyelitis is rare and usually seen in immunocompromised patients. We report a case of Candida parapsilosis osteomyelitis in an immunocompetent patient with no prior surgical history. He went for spinal laminectomy with debridement and drainage. Intraoperative culture grew C. parapsilosis, and the patient was treated with fluconazole.

Extent of craniofacial fungal osteomyelitis in a ketoacidotic patient may predict optic nerve involvement: A case report.

INTRODUCTION: Mucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. Fungal osteomyelitis is a life-threatening condition affectation of the nose and paranasal sinuses within the orofacial region. PRESENTATION OF CASE: We present a 63-year-old diabetic male patient with maxillary mucormycotic osteomyelitis threatening his better seeing eye and review the clinical symptoms, relevant imaging, and management. DISCUSSION: We highlight a rare pattern of craniofacial fungal bone infection with maxillary and orbital involvement that ultimately spared the optic nerve. This case report offers the clinician a review of important clinical and diagnostic findings that can help direct the need for orbital exenteration. CONCLUSION: Maxillary mucormycotic osteomyelitis is an aggressive infection that needs to be addressed promptly to prevent fatal consequences.

Atypical presentations of fungal osteomyelitis during post COVID-19 outbreak - Case series.

Introduction: Mucormycosis and Aspergillosis are opportunistic fungal infections causing significant morbidity and mortality. Post the outbreak of COVID-19, these fungal osteomyelitis have seen a global rise with few atypical presentations noted. Case report: Current case series reports three such atypical presentations of fungal osteomyelitis including mandibular fungal osteomyelitis in two patients, fungal osteomyelitis mimicking space infection in a middle aged male, and suspected mixed fungal osteomyelitis involving maxillary sinus. Aggressive surgical debridement was indicated along with institution of antifungal therapy (Liposomal Amphotericin B, and Posaconazole). The fungal osteomyelitis was successfully treated with surgical and medical management with no recurrence. Discussion: The injudicious use of corticosteroids in COVID-19 patients along with their immunocompromised status increases their susceptibility to opportunistic fungal osteomyelitis. Prompt and aggressive surgical intervention along with antifungal therapy is important after diagnosing fungal osteomyelitis, as a delay could increase the mortality rate considerably.

Skeletal Infections Caused by Coccidioides Species.

BACKGROUND: Coccidioidomycosis represents an endemic and challenging disease, with rare extrapulmonary manifestations. The present review of all published cases of core and extremities osseous coccidioidomycosis aims to describe epidemiology, patients' characteristics, symptoms as well as medical and surgical treatment options and their effectiveness. METHODS: A thorough review of all published skeletal core and extremity infections due to Coccidioides species was conducted. Information regarding demographics, causative fungus, antifungal treatment (AFT), surgical management as well as the infection outcome was recorded. RESULTS: A total of 92 cases of Coccidioides spp. skeletal infections were recorded in 87 patients. The patients' mean age was 35.3 years. The most common site of infection was the spine (82.6%), followed by the foot (6.5%), while the predominant symptom upon presentation was pain (29.9%). Immunosuppressive conditions and/or medications were observed in 21 patients (24.1%). Regarding imaging methods, indicating diagnosis, plain X-rays or CT scans were performed in most patients (50.6%), followed by magnetic resonance imaging (MRI) (47.1%). Most cases were diagnosed through histopathology (62; 71.3%), followed by serology testing (36; 42.4%) and by cultures (35; 40.2%). In 32 cases (36.8%), Coccidioides immitis was cultured, while in the remaining 55 cases (63.2%) the fungus was not further characterized. Regarding AFT, amphotericin B was the preferred agent (52.9%), followed by fluconazole (43.3%). In most cases (78.2%) surgical treatment was also performed. Treatment was successful in 80.5% of cases. CONCLUSIONS: Skeletal core and extremity infections due to Coccidioides spp. represent a severe disease. With the available data, the combination of prolonged proper AFT with surgical intervention seems to be the optimal current therapeutic approach.

Covid-19-associated fungal osteomyelitis of jaws and sinuses: An experience-driven management protocol.

Invasive fungal co-infections with COVID-19 are currently being reported at an alarming rate. Our study explores the importance of early identification of the disease, probable etiopathogenesis, clinical and radiological features and a treatment protocol for COVID-19 Associated Fungal Osteomyelitis of Jaws and Sinuses (CAFOJS). A one-year prospective study from June 2020 to May 2021 was conducted among CAFOJS diagnosed patients at a tertiary care center in South India. Demographic details, COVID-19 infection and treatment history, time taken for initiation of symptoms after COVID-19 diagnosis, medical history and clinical features were recorded. All patients were managed with a standard diagnostic and intervention protocol which included pre-operative and post-operative administration of Inj. Amphotericin B 50 mg (liposomal), early aggressive surgical debridement and tab. Posaconazole GR 300 mg OD for 90 days after discharge. Thirty-nine (78%) patients were diagnosed with CAFOJS out of 50 osteomyelitis patients. 35 patients (90%) were diabetic and 21 patients (54%) were known to receive steroids during the COVID-19 treatment. Sole existence of Mucorales spp. was seen in 30 patients (77%), Aspergillus fumigatus in 2 patients (5%), Curvularia spp. in 2 patients (5%). Concomitant existence of Mucorales and Aspergillus fumigatus was reported in two patients (5%) and Candida albicans in three patients (8%). Patients underwent treatment with standard protocol and no recurrence noted. CAFOJS is a clinical entity with aggressive presentation and warrants early diagnosis and treatment. LAY SUMMARY: Invasive fungal infections of head and neck region cause necrosis of bones affected by it, especially maxilla. Early diagnosis and treatment are advocated in such infections due to its aggressive clinical presentation compared to similar infections before COVID-19 pandemic.

Candida parapsilosis osteomyelitis following dog bite: a case report and review of the literature.

Candida osteomyelitis is uncommon, especially after dog bites. We describe a case of a 63-year-old man without significant comorbidities presenting progressing swelling of the distal interphalangeal joint (DIJ) of right index finger following a dog bite. Despite empiric antibiotic therapy and local medications, there were no clinical signs of improvement. Clinical examination revealed fistula with purulent drainage on the volar region. Even though laboratory data showed inflammatory markers on range, magnetic resonance imaging (MRI) demonstrated signs of osteomyelitis. The patient was taken to exploration and debridement of the bite wound. Culture of the bone biopsy showed growth of Candida parapsilosis. Therefore, the patient was diagnosed with isolated fungal osteomyelitis and was initiated on fluconazole therapy. The treatment was effective and all symptoms were resolved in 8 weeks after the surgery. There were no signs of recurrence after 20 months of follow-up. The patient had no cosmetic abnormalities or sequelae. Concurrently with the description of the case report a review of the literature was provided. According to the authors, there are three main etiopathogenesis for this infection. The first pathogenic mechanism is direct inoculation into the deep tissues through the dog bite. The second hypothesis is direct translocation of the pathogen from the skin to the deep tissue and to the bone. The last mode of transmission is hematogenous dissemination. Fungal osteomyelitis are really rare conditions, especially after dog bites, but nevertheless it should be considered as a possible diagnosis when there is no response to antibiotics.

Mucormycotic osteomyelitis of maxilla post-COVID patient: a case report.

Fungal osteomyelitis is a life-threatening and seldom seen opportunistic infection. It is commonly an affectation of the nose and paranasal sinuses within the orofacial region. It is an aggressive infection that needs to be addressed promptly to prevent fatal consequences. The mode of infection is via the inhalation route and infection begins initially in the nose and paranasal sinuses with subsequent invasion into the vascular tissue, eventually leading to thrombosis and necrosis of nearby hard and soft tissues. Here, we report a case of a 31-year-old male who presented with pain over the upper jaw that was sudden in onset, continuous, dull aching, radiating towards forehead and neck of the left side, aggravates on mastication and relives on its own. He had a history of uncontrolled diabetes mellitus. On further investigation, using diagnostic and Interventional aids, a final diagnosis of mucormycotic osteomyelitis of the maxilla was made.

Sternectomy for Candida albicans sternal osteomyelitis after left ventricular assist device implantation.

Fungal osteomyelitis is an uncommon complication after cardiac surgery and associated with high mortality. A case of Candida albicans and Staphylococcus epidermidis osteomyelitis with device infection after implantation of a left ventricular assist device in a 60-year-old male patient is presented here. After clinical identification and confirmation with microbiological examinations and fluorodeoxyglucose positron emission tomography (FDG-PET) scan, debridement was performed. Surgical specimens grew C. albicans and S. epidermidis. Fluconazole, daptomycin, and negative pressure wound therapy were initiated, but failed to achieve healing. Total sternectomy and pectoralis flap reconstruction were performed. There was no recurrent infection for C. albicans on a prolonged antifungal regime. The combination of antifungal therapy and aggressive surgical debridement may be useful to control fungal osteomyelitis.

Mandibular mucormycosis following SARS-CoV-2 infection - A case report and review of literature.

BACKGROUND: The second wave of COVID-19 pandemic has seen an unprecedented rise in the number of mucormycosis cases worldwide and in India particularly. This otherwise rare fungal infection has become an endemic among patients who have recovered from recent SARS-CoV-2 infection. Among the different types of mucormycosis, rhino-orbital-cerebral involvement has mainly been observed in the recent surge of cases. Very few cases of mucormycosis of mandible have been reported in literature and none in COVID-19 patients. We report a case of isolated mandibular mucormycosis in a COVID- 19 patient, with no other predisposing comorbidities.Case report.A 39 year old patient recently recovered from COVID-19 presented with typical symptoms of osteomyelitis which was confirmed using computed tomography of face. He underwent thorough debridement and curettage and tissue was sent for culture, special staining and biopsy. RESULT: Diagnosis of mucormycosis was confirmed based on postoperative biopsy and special staining. He was further managed with complete course of appropriate antifungal therapy. CONCLUSION: Mucormycosis is a fulminant and aggressive infection which requires prompt diagnosis and intervention. Early referral to a maxillofacial surgeon by physicians and general dental practitioners on seeing signs and symptoms of secondary fungal infections involving maxilla or mandible in patients with history of SARS-CoV-19 infection can improve prognosis.

Mucormycosis osteomyelitis after anterior cruciate ligament reconstruction: treatment and outcomes of 21 reported cases.

AIMS: Our purpose was to describe an unusual series of 21 patients with fungal osteomyelitis after an anterior cruciate ligament reconstruction (ACL-R). METHODS: We present a case-series of consecutive patients treated at our institution due to a severe fungal osteomyelitis after an arthroscopic ACL-R from November 2005 to March 2015. Patients were referred to our institution from different areas of our country. We evaluated the amount of bone resection required, type of final reconstructive procedure performed, and Musculoskeletal Tumor Society (MSTS) functional score. RESULTS: A total of 21 consecutive patients were included in the study; 19 were male with median age of 28 years (IQR 25 to 32). All ACL-R were performed with hamstrings autografts with different fixation techniques. An oncological-type debridement was needed to control persistent infection symptoms. There were no recurrences of fungal infection after median of four surgical debridements (IQR 3 to 6). Five patients underwent an extensive curettage due to the presence of large cavitary lesions and were reconstructed with hemicylindrical intercalary allografts (HIAs), preserving the epiphysis. An open surgical debridement was performed resecting the affected epiphysis in 15 patients, with a median bone loss of 11 cm (IQR 11.5 to 15.6). From these 15 cases, eight patients were reconstructed with allograft prosthesis composites (APC); six with tumour-type prosthesis (TTP) and one required a femoral TTP in combination with a tibial APC. One underwent an above-the-knee amputation. The median MSTS functional score was 20 points at a median of seven years (IQR 5 to 9) of follow-up. CONCLUSION: This study suggests that mucormycosis infection after an ACL-R is a serious complication. Diagnosis is usually delayed until major bone destructive lesions are present. This may originate additional massive reconstructive surgeries with severe functional limitations for the patients.Level of evidence: IVCite this article: Bone Joint Open 2020;2(1):3-8.

Fungal osteomyelitis and soft tissue infections: Simple solutions to uncommon scenarios.

INTRODUCTION: Fungal osteoarticular/soft tissue infections (FOaSI) are an uncommon entity with protracted course due to variability in clinical picture, slow progression; resulting in misdiagnosis with empirical therapy. Recent studies have shown an alarming emergence of FOaSI in immunocompetent individuals with high mortality rates. This study recommends a protocol for managing these complex and confusing scenarios. METHODOLOGY: We have retrospectively analysed patients with FOaSI between January 2014 and December 2016, with a minimum 12 months follow up. RESULTS: 8 cases (6 male, 2 female) with a mean age of 42.88 years (26-53) presented to us 45 days (3-365) after initial symptoms. They underwent mean 3 procedures before being diagnosed with a fungal infection. Deep tissue cultures grew 9 fungi and 6 bacteria, commonest fungus being Candida sp (n = 4), treated with appropriate antifungals and antibiotics. Infection remission was achieved in 7/8 (87.5%) cases at 27.1 months (19-45) follow-up with 1 mortality. Excellent functional results as per our criteria were seen in 5 cases (62.5%) with 1 talus excision, 1 ray amputation and 1 mortality. CONCLUSIONS: This study highlights the significance of implementing a simple rule such as obtaining fungal cultures in every case of bone and soft tissue infections. Standardisation of treatment may not be the ideal solution, since different fungi have different growth patterns and invasiveness. A simple protocol of customising the medico- surgical treatment with an open ended discussion between the surgeons, microbiologists, pathologists and infectious disease specialists forms the cornerstone to success.

Limb-saving Knee Arthrodesis with a Silver-coated Arthrodesis Rod in a Patient with Aspergillus Osteomyelitis of the Knee.

Aspergillus osteomyelitis can be a very debilitating disease with an associated mortality of up to 25%. Silver is well known for its broad antimicrobial properties including activity against fungi and the coating of orthopaedic implants with silver has been reported to be successful in complex cases. We report for the first time on a complicated case of Aspergillus osteomyelitis affecting the left knee in a patient with a chronic lymphoid leukaemia treated with appropriate surgical debridement, local and systemic antibiotic and antimycotic therapy, as well as staged surgical treatment with final limb-saving arthrodesis by using a custom-made microsilver coated arthrodesis rod. How to cite this article: Ismat A, Alt V, Heiss C, et al. Limb-saving Knee Arthrodesis with a Silver-coated Arthrodesis Rod in a Patient with Aspergillus Osteomyelitis of the Knee. Strategies Trauma Limb Reconstr 2020;15(2):121-125.

Maxillary rehabilitation after complete destruction by fungal osteomyelitis.

Treatment of uncommon fungal infection such as Rhinosporidiosis is challenging, especially when occurring in a non-immunocompromised patient in non-invasive form. Extensive involvement, extending into maxillary jawbone would need aggressive, chemotherapeutic and surgical approach. There are few reports of successful rehabilitation of maxillary jaw with dental implants after treatment of such fungal infection. After adequate medical treatment, the iliac graft and recombinant bone morphogenetic protein-2 was effectively utilized to reconstruct the lost maxillary bone. Later, dental implants were placed, that osseointegrated well.

Phaeohyphomycotic Rhinitis Caused by Bipolaris hawaiiensis in a Horse.

This case represents the first reported case of Bipolaris hawaiiensis infection in an equid, and its aggressive clinical course. This case provides important descriptive and prognostic information for horses diagnosed with phaeohyphomycotic rhinitis. A 19-year-old American Quarter Horse mare was presented for second opinion of stertor and exercise intolerance of four-month duration. Endoscopy revealed generalized, proximal nasal edema, and computed tomography identified a soft tissue mass eroded through the rostral nasal bone. Biopsy of the mass was identified as a fungal granuloma caused by B. hawaiiensis resulting in chronic invasive fungal rhinitis. Treatment options were limited because of invasive infection, financial constraints, fungal sensitivity results, and published accounts of in vivo behavior of the organism. The infection progressed, resulting in euthanasia. In this case of equine phaeohyphomycosis, B. hawaiiensis was likely traumatically introduced into the patient's nasal cavity. Its aggressive nature in an apparently immunocompetent patient is noteworthy, in the face of surgical debridement and attempted medical therapy. Therapeutic decisions were challenging in this case based on limited in vivo efficacy data in equids, pharmacokinetic challenges with available antifungal agents, and client-driven limitations regarding management of airway restriction.

Maxillary Fungal Osteomyelitis: A Review of Literature and Report of a Rare Case.

Fungal osteomyelitis is a life-threatening and seldom seen opportunistic infection. It is commonly an affectation of the nose and paranasal sinuses within the orofacial region. It is an aggressive infection that needs to be addressed promptly to prevent fatal consequences. Here, we present a case of a 62-year-old female who presented with complaints of pain and pus discharge from the extraction socket of the left maxillary 23, 24, 25, 26 teeth. She had a history of uncontrolled diabetes mellitus. On further investigation, using diagnostic and Interventional aids, a final diagnosis of maxillary fungal osteomyelitis was made. The infective fungal agents were a mixture of Mucorales and Aspergillus species. A review of all literatures on the subject in the past 13 years using different search engines showed that craniofacial fungal infections with primary maxillary involvement are a rare phenomenon. The primary aim of reporting this case, therefore, is to highlight its rarity, presentation, management and most importantly the outcome of management.