Fracture-related infection of the lower limb caused by Mucor velutinosus: amputation or salvation?

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Alexander Eijkenboom, Matthias Militz, Thomas Kern, Maurizio Papetti, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4300379/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Fracture-related infections caused by mucormycosis are rare and potentially fatal. Evidence-based experience with its treatment is limited and surgical management ranges from limb salvage to amputation, with indications not always clear. Case presentation: A 56-year-old woman was admitted after an aircraft accident, sustaining major trauma injuries, including a Gustilo-Anderson type III open ankle joint fracture. Following initial damage control surgery with external fixation, the patient developed a fracture-related infection in the ankle caused by Mucor velutinosus . Despite its invasive growth and tenacity, surgical debridement combined with systemic and local antifungal therapy led to remission in this immunocompetent patient. The ankle arthrodesis achieved bone union with a hexapod fixator 10 months post trauma. Conclusion: In the treatment of invasive mucormycosis, a multidisciplinary approach is necessary. Through apt diagnosis and thorough treatment by experienced surgeons, infectiologists and pathologists successful limb salvage may be attained in patients with an intact immune system and amputation can be prevented. mucor velutinosus fungal infection fracture-related infection amphotericin B arthrodesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Mucormycosis is a rare angioinvasive fungal infection, caused by filamentous fungi, with a high morbidity and a mortality rate ranging from 40–80% [ 1 ]. Mucor spores are ubiquitous in nature [ 2 ]. Usually, manifestations were observed as rhino-orbital-cerebral mucormycosis, followed by cutaneous and pulmonary mucormycosis [ 2 , 3 ]. Mucormycosis typically affects immunocompromised patients with underlying conditions such as diabetes mellitus, hematologic malignancies, organ transplants and neutropenia [ 1 , 2 , 4 ]. It has also become a new hazard in the treatment of patients with Coronavirus disease 2019 who were receiving high-dose corticosteroids [ 5 ]. Osteoarticular infections caused by fungi, are extremely rare and are mostly associated with Candida or Aspergillus [ 6 ]. Case report A 56-year-old female with no medical history apart from cervical spinal canal stenosis and hypothyroidism was admitted following a light aircraft crash. A contrast-enhanced whole body computer tomography (CT) scan was performed, revealing major trauma injuries including fractures of the cervical, thoracic and lumbar spine, bilateral rib fractures, and a sternal fracture. Additionally, a Gustilo-Anderson type III open ankle joint fracture of the right lower extremity were detected ( Fig. 1ab ). Intravenous antibiotics with ampicillin/sulbactam (2g/1g three times daily) were initiated preoperatively and continued for 72 hours due to the type III open fracture. Following admission, immediate reduction of the upper ankle joint and stabilization by external fixation were performed in accordance with damage control principles. The soft tissue injury was surgically debrided, and gentamicin-impregnated collagen fleece was applied. Negative pressure wound therapy (NPWT) was used for temporary wound closure. Four days after trauma, the patient underwent anterior cervical disc fusion and internal fixation of the thoracolumbar junction spine fracture. Following surgery, the patient developed hospital-acquired pneumonia, which required escalation of antibiotic treatment to piperacillin/tazobactam (4.5g four times daily). After 7 days, pulmonary function recovered sufficiently, and antibiotic therapy was discontinued. The lower limb fracture was definitively treated through open reduction and internal fixation on day 10. A locking plate was used for the distal fibula, along with tibio-fibular syndesmotic screw fixation and a suture anchor for deltoid ligament reconstruction (Fig. 1 c). Additionally, the medial wound was closed with staples during the same surgery, while the external fixator remained to aid in soft tissue healing. On day 16, the external fixator was removed. On day 38, a surgical wound revision was performed due to delayed healing and continuous serosanguinous drainage of the medial ankle wound. The revision included debridement of the medial malleolus and lavage of the upper ankle joint. A fracture-related infection (FRI) of the distal tibia was diagnosed upon detection of Staphylococcus epidermidis ( S. epidermidis ), and cotrimoxazole (960mg twice daily) was orally administered. The patient underwent repeated surgical debridement including removal of the suture anchor, resulting in a growing soft tissue defect at the medial malleolus. The antibiotic therapy was changed to linezolid (600mg twice daily) due to a change in the antibiotic sensitivity of the cultured S. epidermidis . On day 65, during surgical debridement, Mucor velutinosus (M. velutinosus) was first detected in cultures and histopathology. Furthermore, the tibia exhibited necroses with lack of cancellous bone bleeding (Fig. 2 ). An antifungal therapy for osseous mucormycosis was initiated with posaconazole (600mg first day, then 300mg daily). Systemic inflammatory markers were almost normal (CRP 1.7 mg/dl, cut-off < 1.0 mg/dl; WBC 7.5/nl) and the patient presented stable. During subsequent debridement surgeries, positive cultures for M. velutinosus and S. epidermidis were found in biopsies of the upper ankle and distal fibula. All foreign implants from the distal fibula were removed on day 70. The upper ankle joint showed a chronic FRI and septic cartilage destruction. A CT angiography revealed sufficient arterial perfusion of the lower extremities without relevant stenoses. Two therapeutic options were discussed with the patient. The first option was below-knee amputation for rapid recovery and weight-bearing activities, assuming proper wound healing. The second option was limb salvage, including ongoing antibiotic and antifungal therapy, debridement, bone reconstruction, and soft tissue reconstruction under continuous clinical monitoring. The concept of limb salvage was considered feasible for the immunocompetent, stable patient. Limb salvage was chosen according to the patient's wishes. On day 80, the upper ankle joint surfaces, the medial and lateral malleolus were resected (Fig. 3 a). Temporary bone defect management for the former upper ankle joint was achieved using polymethylmethacrylate (PMMA) cement spacers impregnated with amphotericin B (AmB, 200mg in 20g PMMA) and vancomycin (1g in 20g PMMA) (Fig. 3 b). Additionally, the antifungal treatment was escalated to intravenous liposomal AmB (250mg daily, 3-5mg/kg bodyweight daily). Weekly debridement was repeated for 5 weeks until M. velutinosus and S. epidermidis were no longer detectable in tissue samples, and the resection margin was microscopically confirmed to be free of mucor hyphae. As a result of these debridement surgeries, a 5 cm bone defect, as well as a medial soft tissue defect, remained. Linezolid was discontinued. A Hoffmann Limb Reconstruction Frame (LRF) hexapod fixator (Stryker®, Michigan, USA) was applied on day 114 for arthrodesis of the upper ankle joint after final bone debridement. The considerable soft tissue defect required limb shortening and fixation of the foot in a varus position of 30° for successful secondary wound closure ( Fig. 3cd ). This approach avoided the need for free flap surgery. The wound consolidated after 3 weeks. Intravenous liposomal AmB was discontinued on day 127, four weeks after initiation. The hexapod fixator was used to continuously correct the combined bony and soft tissue deformity over a period of 50 days, finishing on day 180. A neutral position of the tibiotalar arthrodesis was achieved with sufficient and stable soft tissue coverage. Routine clinical examinations did not reveal signs of infection, and radiological imaging indicated progressing bone union. The LRF fixator was removed after 6 months. The healing arthrodesis was further immobilized using a walking boot orthosis. Physical therapy was intensified, and the patient was able to walk without pain. Radiological imaging showed partial but sufficient union of the ankle arthrodesis 10 months after the reconstruction surgery (Fig. 3 e). The patient currently exhibits a healthy gait and posture by compensating for the leg length discrepancy with a minor shoe lift ( Fig. 4 ). No further surgical treatment is planned due to the patient's lack of pain and good mobility. Discussion Interestingly our patient did not suffer from pre-existing medical conditions, which makes an FRI caused by M. velutinosus even more remarkable. However, a metanalysis has shown that major trauma may increase the risk for mucormycosis [ 3 ]. The origin of M. velutinosus in our patient remains unclear. Taj-Aldeen et al. suggested that 56% of these infections are caused by direct inoculation during trauma, 24% by hematogenous dissemination, and 21% by contiguous spread [ 7 ]. In his study, the median diagnostic delay of mucormycosis was 60 days. This is reflected in our case, where M. velutinosus was first detected on day 65. The osseous mucormycosis of our patient was classified as an FRI since the pathogenic bacteria and fungi were present at the fracture site and implants [ 8 ]. Hereby FRIs or any osteoarticular infections caused by fungi, are extremely rare and are mostly associated with Candida or Aspergillus [ 6 ]. Osseous mucormycosis remains an exception in an already rare disease. Current literature only exists regarding individual case reports of immunocompromised patients [ 7 , 9 ]. Case reports of mucormycotic FRI are rare and different treatment regimens are described [ 7 , 9 ]: Treatment suggestions included surgical debridement, systemic antifungal therapy and often amputation of affected lower limbs [ 10 , 11 ]. Case reports with limb salvage in well vascularized body regions such as the hand have also been reported [ 12 ]. Amputation was performed in more instances than not and seemed a possibility for our patient as well, considering the invasiveness of mucormycosis with bone and soft tissue destruction leading to high mortality [ 7 , 10 , 11 , 13 ]. After diagnosing FRI in our patient, we initiated anti-infective therapy, including surgical debridement, removal of foreign implants, and adjuvant systemic antimycotics with oral posaconazole. Due to our patient's immunocompetence and lack of medical history, we pursued the concept of limb salvage under close clinical observation. After 6 weeks of unsuccessful eradication of M. velutinosus with posaconazole, the guidelines of the European Society of Clinical Microbiology and Infectious Diseases recommend escalation to intravenous liposomal AmB for the treatment of invasive fungal infections [ 14 ]. An earlier escalation may have led to earlier eradication of the infection. However, it is important to note that AmB can lead to serious adverse effects, such as nephrotoxicity [ 15 , 16 ]. Due to the absence of acute signs of infection, an escalation was initially waived. Our therapy also involved the local application of AmB using PMMA spacers to achieve higher antifungal concentrations on site. This method has been proven to be highly effective in treating bacterial infections in cases where poorly vascularized bone is not accessible to systemic intravenous anti-infective therapy [ 17 , 18 ]. Hyperbaric oxygenation therapy (HBOT) can be considered as an additional therapeutic tool for treating mucormycosis. Data on the effectiveness of HBOT in treating fungal infections is limited and inconsistent. HBOT has been suggested to promote wound healing and inhibit fungal growth, and it has been proposed as an adjunct therapy to antifungal and surgical treatments for rhinocerebral mucormycosis [ 19 , 20 ]. In this case radical debridement of the upper ankle joint combined with antifungal medication, resulted in the eradication of the fungal infection. This procedure resulted in a bone defect of approximately 5 cm. Our interdisciplinary team discussed various reconstruction options, including internal fixation, allograft or autograft bone transplants, external fixation, and soft tissue reconstruction with a free flap. However, due to the high risk of infection relapse, a hexapod fixator was chosen as a reliable external fixation method for complex lower limb injuries [ 21 ]. Limb salvage was ultimately achieved, with a follow-up of 12 months post trauma. In the era of standard operating procedures and algorithms, the authors suggest the following approach in immunocompetent patients with mucormycotic FRI: Treatment by an experienced team of surgeons and infectiologists is recommended. Tissue samples should also be examined for fungal pathogens using cultures and histopathology. After pathogen identification and diagnosis of mucormycotic FRI, antifungal treatment with oral posaconazole or, if possible, intravenous liposomal AmB is recommended. Early and complete removal of foreign implants as well as necrotic tissue is inevitable during the debridement of soft tissue and bone. Local antifungal treatment options, such as AmB-infused PMMA spacers, can be utilized. Adjunct HBOT may be considered. Reconstruction of soft tissue and bone can be performed once tissue samples test negative and the ongoing FRI is eliminated. In cases of rapid progression of mucormycosis or lack of reconstructive options, the treatment course of limb salvage may be aborted, with amputation available as a fallback. Conclusion Multidisciplinary cooperation is crucial for salvaging the lower extremity in cases of mucormycotic FRI. This begins with early histopathological and microbiological examinations, which allow for timely surgical and antifungal treatment. Despite the invasive growth of mucormycetes, it is important to avoid hasty decisions regarding amputation, especially in patients with no comorbidities and an intact immune system. Limb salvage is a viable option in a setting where ongoing clinical reevaluation is possible and immediate surgical intervention is available in case of infection aggravation. Declarations Funding: No funds, grants, or other support was received. Author Contribution A.E. and S.H. wrote the main manuscript text. A.E., V.K. and S.H. prepared the figures. A.E., M.M., T.K., M.P. and S.H. were involved with direct patient contact. A.E., T.K. , V.K. and S.H. performed significant data collection and analysis. A.E., M.P. and S.H. did extensive literature review for treatment course as well as for the manuscript. All authors reviewed the manuscript before submission. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Consent to participate and publish: The participant has consented to the submission of the case report to the journal. References Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19: e405–e421. Skiada A, Rigopoulos D, Larios G, et al. Global epidemiology of cutaneous zygomycosis. Clin Dermatol 2012; 30: 628–632. Jeong W, Keighley C, Wolfe R, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clinical Microbiology and Infection 2019; 25: 26–34. Ghuman H, Voelz K. Innate and Adaptive Immunity to Mucorales. Journal of Fungi ; 3. Epub ahead of print 1 September 2017. DOI: 10.3390/JOF3030048 . Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe 2022; 3: e543. De Meo D, Cera G, Ceccarelli G, et al. Candida fracture-related infection: a systematic review. J Bone Jt Infect 2021; 6: 321. Taj-Aldeen SJ, Gamaletsou MN, Rammaert B, et al. Bone and joint infections caused by mucormycetes: A challenging osteoarticular mycosis of the twenty-first century. Med Mycol 2017; 55: 691. Metsemakers WJ, Morgenstern M, McNally MA, et al. Fracture-related infection: A consensus on definition from an international expert group. Injury 2018; 49: 505–510. Asperges E, Albi G, Truffelli F, et al. Fungal Osteomyelitis: A Systematic Review of Reported Cases. Microorganisms ; 11. Epub ahead of print 1 July 2023. DOI: 10.3390/MICROORGANISMS11071828/S1 . Coerdt KM, Zolper EG, Starr AG, et al. Cutaneous mucormycosis of the lower extremity leading amputation in two diabetic patients. Arch Plast Surg 2021; 48: 231–236. Bhatt M, Soneja M, Fazal F, et al. Two cases of Osteoarticular Mucor menace: A diagnostic and management conundrum. Drug Discov Ther 2018; 12: 374–378. Tiourin E, Kanack M, Ng W, et al. Mucor Osteomyelitis of the Distal Radius Necessitating Ulnocarpal Fusion. Cureus ; 13. Epub ahead of print 20 January 2021. DOI: 10.7759/CUREUS.12813 . Spuehler D, Fuchs J, Hainich J. Mucor osteomyelitis after traumatic forearm amputation in a 38-year-old patient. Case Reports Plast Surg Hand Surg; 10. Epub ahead of print 2023. DOI: 10.1080/23320885.2023.2259468 . Cornely OA, Cuenca-Estrella M, Meis JF, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect 2014; 20 Suppl 3: 1–4. Loo AS, Muhsin SA, Walsh TJ. Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B. Expert Opin Drug Saf 2013; 12: 881–895. Sabra R, Branch RA. Amphotericin B nephrotoxicity. Drug Saf 1990; 5: 94–108. Hanssen AD, Spangehl MJ. Treatment of the infected hip replacement. Clin Orthop Relat Res 2004; 420: 63–71. Joseph TN, Chen AL, Di Cesare PE. Use of antibiotic-impregnated cement in total joint arthroplasty. J Am Acad Orthop Surg 2003; 11: 38–47. Couch L, Theilen F, Mader JT. Rhinocerebral mucormycosis with cerebral extension successfully treated with adjunctive hyperbaric oxygen therapy. Arch Otolaryngol Head Neck Surg 1988; 114: 791–794. Ferguson BJ, Mitchell TG, Moon R, et al. Adjunctive hyperbaric oxygen for treatment of rhinocerebral mucormycosis. Rev Infect Dis 1988; 10: 551–559. Marwan Y, Turner J, Senan R, et al. Circular external fixation for revision of failed tibia internal fixation. Eur J Orthop Surg Traumatol. Epub ahead of print 2023. DOI: 10.1007/S00590-023-03660-5 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4300379","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":294351402,"identity":"9d15d169-9bff-4c8b-8188-d5242cadebf1","order_by":0,"name":"Alexander Eijkenboom","email":"data:image/png;base64,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","orcid":"","institution":"Department of Septic and Reconstructive Surgery, BG Unfallklinik Murnau","correspondingAuthor":true,"prefix":"","firstName":"Alexander","middleName":"","lastName":"Eijkenboom","suffix":""},{"id":294351404,"identity":"da976e68-c1f0-415f-b088-029385f3fb0c","order_by":1,"name":"Matthias Militz","email":"","orcid":"","institution":"Department of Septic and Reconstructive Surgery, BG Unfallklinik Murnau","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Militz","suffix":""},{"id":294351410,"identity":"1ff4c090-0aa6-4ddb-b49d-24e65646a6ff","order_by":2,"name":"Thomas Kern","email":"","orcid":"","institution":"Department of Septic and Reconstructive Surgery, BG Unfallklinik Murnau","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Kern","suffix":""},{"id":294351418,"identity":"75497de9-747e-4605-9040-ada5a0a9018a","order_by":3,"name":"Maurizio Papetti","email":"","orcid":"","institution":"Department of Septic and Reconstructive Surgery, BG Unfallklinik Murnau","correspondingAuthor":false,"prefix":"","firstName":"Maurizio","middleName":"","lastName":"Papetti","suffix":""},{"id":294351420,"identity":"b029df13-34d6-45e3-879a-010dc47fe9cf","order_by":4,"name":"Veit Krenn","email":"","orcid":"","institution":"Department of Pathology, Trier MVZ of Pathology","correspondingAuthor":false,"prefix":"","firstName":"Veit","middleName":"","lastName":"Krenn","suffix":""},{"id":294351421,"identity":"93709448-b784-4fab-8cfb-0ed9327d3236","order_by":5,"name":"Simon Hackl","email":"","orcid":"","institution":"Department of Septic and Reconstructive Surgery, BG Unfallklinik Murnau","correspondingAuthor":false,"prefix":"","firstName":"Simon","middleName":"","lastName":"Hackl","suffix":""}],"badges":[],"createdAt":"2024-04-21 10:41:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4300379/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4300379/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55538400,"identity":"5922d1d0-2438-4fd9-ab85-f36e1ab08dbf","added_by":"auto","created_at":"2024-04-29 16:49:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1499320,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eType III open ankle joint fracture\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003ePhotograph of the open ankle joint fracture with protruding medial malleolus through skin at admission \u003cstrong\u003eb\u003c/strong\u003e 3-D rendered image from CT scan performed at admission visualizing a distal fracture of the fibula and dislocation of the tibiotalar joint \u003cstrong\u003ec\u003c/strong\u003eOsteosynthesis of the fibula by plate and reconstruction of the deltoid ligament by suture anchor with additional external fixation\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4300379/v1/07802d7570145d9bfe7a25ba.png"},{"id":55538397,"identity":"0981f9f0-5ef3-49eb-97a5-28c28fa29627","added_by":"auto","created_at":"2024-04-29 16:49:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1515361,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMucormycosis of bone tissue\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eAvital medial malleolus and soft tissue defect after removal of the suture anchor \u003cstrong\u003eb \u003c/strong\u003eMicroscopic image (420x) of the necrotic bone. Grocott's methenamine silver stain showing hyphae of \u003cem\u003eM. velutinosus \u003c/em\u003e(arrow)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4300379/v1/9bb621e1a0bfa0a83076af9a.png"},{"id":55538401,"identity":"49b7d90b-3a90-48d0-8ba9-015d0395f36c","added_by":"auto","created_at":"2024-04-29 16:49:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1179180,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRadiographs of the lower leg\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eResection of the upper ankle joint, including the medial and lateral malleolus, and removal of all foreign implants \u003cstrong\u003eb\u003c/strong\u003e AmB and vancomycin infused PMMA-spacer during debridement phase \u003cstrong\u003ec,d \u003c/strong\u003eHexapod fixator to correct varus deformity \u003cstrong\u003ee\u003c/strong\u003ePartial bone union after removal of the hexapod fixator\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4300379/v1/05e8659e8a12acd36150122c.png"},{"id":55538398,"identity":"a184aed4-738c-42b4-a2f5-b885ec8d19ad","added_by":"auto","created_at":"2024-04-29 16:49:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1268746,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical presentation 1 year post trauma\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eAnterior view showing reduced muscle mass of right lower limb after ankle arthrodesis \u003cstrong\u003eb \u003c/strong\u003eLateral clinical view showing the shoe lift\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4300379/v1/72b984b0d6084dd76c2a0fb9.png"},{"id":55757252,"identity":"f48967e5-551a-4809-b74b-990531c75c40","added_by":"auto","created_at":"2024-05-02 17:27:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5113749,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4300379/v1/c419d534-9581-446f-beb4-eabc23725091.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fracture-related infection of the lower limb caused by Mucor velutinosus: amputation or salvation?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMucormycosis is a rare angioinvasive fungal infection, caused by filamentous fungi, with a high morbidity and a mortality rate ranging from 40\u0026ndash;80% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Mucor spores are ubiquitous in nature [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Usually, manifestations were observed as rhino-orbital-cerebral mucormycosis, followed by cutaneous and pulmonary mucormycosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Mucormycosis typically affects immunocompromised patients with underlying conditions such as diabetes mellitus, hematologic malignancies, organ transplants and neutropenia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It has also become a new hazard in the treatment of patients with Coronavirus disease 2019 who were receiving high-dose corticosteroids [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Osteoarticular infections caused by fungi, are extremely rare and are mostly associated with Candida or Aspergillus [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 56-year-old female with no medical history apart from cervical spinal canal stenosis and hypothyroidism was admitted following a light aircraft crash. A contrast-enhanced whole body computer tomography (CT) scan was performed, revealing major trauma injuries including fractures of the cervical, thoracic and lumbar spine, bilateral rib fractures, and a sternal fracture. Additionally, a Gustilo-Anderson type III open ankle joint fracture of the right lower extremity were detected (\u003cstrong\u003eFig.\u0026nbsp;1ab\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eIntravenous antibiotics with ampicillin/sulbactam (2g/1g three times daily) were initiated preoperatively and continued for 72 hours due to the type III open fracture. Following admission, immediate reduction of the upper ankle joint and stabilization by external fixation were performed in accordance with damage control principles. The soft tissue injury was surgically debrided, and gentamicin-impregnated collagen fleece was applied. Negative pressure wound therapy (NPWT) was used for temporary wound closure. Four days after trauma, the patient underwent anterior cervical disc fusion and internal fixation of the thoracolumbar junction spine fracture. Following surgery, the patient developed hospital-acquired pneumonia, which required escalation of antibiotic treatment to piperacillin/tazobactam (4.5g four times daily). After 7 days, pulmonary function recovered sufficiently, and antibiotic therapy was discontinued. The lower limb fracture was definitively treated through open reduction and internal fixation on day 10. A locking plate was used for the distal fibula, along with tibio-fibular syndesmotic screw fixation and a suture anchor for deltoid ligament reconstruction (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ec). Additionally, the medial wound was closed with staples during the same surgery, while the external fixator remained to aid in soft tissue healing. On day 16, the external fixator was removed.\u003c/p\u003e\n\u003cp\u003eOn day 38, a surgical wound revision was performed due to delayed healing and continuous serosanguinous drainage of the medial ankle wound. The revision included debridement of the medial malleolus and lavage of the upper ankle joint. A fracture-related infection (FRI) of the distal tibia was diagnosed upon detection of \u003cem\u003eStaphylococcus epidermidis\u003c/em\u003e (\u003cem\u003eS. epidermidis\u003c/em\u003e), and cotrimoxazole (960mg twice daily) was orally administered. The patient underwent repeated surgical debridement including removal of the suture anchor, resulting in a growing soft tissue defect at the medial malleolus. The antibiotic therapy was changed to linezolid (600mg twice daily) due to a change in the antibiotic sensitivity of the cultured \u003cem\u003eS. epidermidis\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eOn day 65, during surgical debridement, \u003cem\u003eMucor velutinosus (M. velutinosus)\u003c/em\u003e was first detected in cultures and histopathology. Furthermore, the tibia exhibited necroses with lack of cancellous bone bleeding (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). An antifungal therapy for osseous mucormycosis was initiated with posaconazole (600mg first day, then 300mg daily). Systemic inflammatory markers were almost normal (CRP 1.7 mg/dl, cut-off \u0026lt;\u0026thinsp;1.0 mg/dl; WBC 7.5/nl) and the patient presented stable.\u003c/p\u003e\n\u003cp\u003eDuring subsequent debridement surgeries, positive cultures for \u003cem\u003eM. velutinosus\u003c/em\u003e and \u003cem\u003eS. epidermidis\u003c/em\u003e were found in biopsies of the upper ankle and distal fibula. All foreign implants from the distal fibula were removed on day 70. The upper ankle joint showed a chronic FRI and septic cartilage destruction. A CT angiography revealed sufficient arterial perfusion of the lower extremities without relevant stenoses.\u003c/p\u003e\n\u003cp\u003eTwo therapeutic options were discussed with the patient. The first option was below-knee amputation for rapid recovery and weight-bearing activities, assuming proper wound healing. The second option was limb salvage, including ongoing antibiotic and antifungal therapy, debridement, bone reconstruction, and soft tissue reconstruction under continuous clinical monitoring. The concept of limb salvage was considered feasible for the immunocompetent, stable patient. Limb salvage was chosen according to the patient\u0026apos;s wishes.\u003c/p\u003e\n\u003cp\u003eOn day 80, the upper ankle joint surfaces, the medial and lateral malleolus were resected (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea). Temporary bone defect management for the former upper ankle joint was achieved using polymethylmethacrylate (PMMA) cement spacers impregnated with amphotericin B (AmB, 200mg in 20g PMMA) and vancomycin (1g in 20g PMMA) (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb). Additionally, the antifungal treatment was escalated to intravenous liposomal AmB (250mg daily, 3-5mg/kg bodyweight daily). Weekly debridement was repeated for 5 weeks until \u003cem\u003eM. velutinosus\u003c/em\u003e and \u003cem\u003eS. epidermidis\u003c/em\u003e were no longer detectable in tissue samples, and the resection margin was microscopically confirmed to be free of mucor hyphae. As a result of these debridement surgeries, a 5 cm bone defect, as well as a medial soft tissue defect, remained. Linezolid was discontinued.\u003c/p\u003e\n\u003cp\u003eA Hoffmann Limb Reconstruction Frame (LRF) hexapod fixator (Stryker\u0026reg;, Michigan, USA) was applied on day 114 for arthrodesis of the upper ankle joint after final bone debridement. The considerable soft tissue defect required limb shortening and fixation of the foot in a varus position of 30\u0026deg; for successful secondary wound closure (\u003cstrong\u003eFig.\u0026nbsp;3cd\u003c/strong\u003e). This approach avoided the need for free flap surgery. The wound consolidated after 3 weeks. Intravenous liposomal AmB was discontinued on day 127, four weeks after initiation. The hexapod fixator was used to continuously correct the combined bony and soft tissue deformity over a period of 50 days, finishing on day 180.\u003c/p\u003e\n\u003cp\u003eA neutral position of the tibiotalar arthrodesis was achieved with sufficient and stable soft tissue coverage. Routine clinical examinations did not reveal signs of infection, and radiological imaging indicated progressing bone union. The LRF fixator was removed after 6 months. The healing arthrodesis was further immobilized using a walking boot orthosis. Physical therapy was intensified, and the patient was able to walk without pain. Radiological imaging showed partial but sufficient union of the ankle arthrodesis 10 months after the reconstruction surgery (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ee). The patient currently exhibits a healthy gait and posture by compensating for the leg length discrepancy with a minor shoe lift (\u003cstrong\u003eFig.\u0026nbsp;4\u003c/strong\u003e). No further surgical treatment is planned due to the patient\u0026apos;s lack of pain and good mobility.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eInterestingly our patient did not suffer from pre-existing medical conditions, which makes an FRI caused by \u003cem\u003eM. velutinosus\u003c/em\u003e even more remarkable. However, a metanalysis has shown that major trauma may increase the risk for mucormycosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The origin of \u003cem\u003eM. velutinosus\u003c/em\u003e in our patient remains unclear. Taj-Aldeen et al. suggested that 56% of these infections are caused by direct inoculation during trauma, 24% by hematogenous dissemination, and 21% by contiguous spread [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In his study, the median diagnostic delay of mucormycosis was 60 days. This is reflected in our case, where \u003cem\u003eM. velutinosus\u003c/em\u003e was first detected on day 65.\u003c/p\u003e \u003cp\u003eThe osseous mucormycosis of our patient was classified as an FRI since the pathogenic bacteria and fungi were present at the fracture site and implants [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Hereby FRIs or any osteoarticular infections caused by fungi, are extremely rare and are mostly associated with Candida or Aspergillus [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Osseous mucormycosis remains an exception in an already rare disease. Current literature only exists regarding individual case reports of immunocompromised patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCase reports of mucormycotic FRI are rare and different treatment regimens are described [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]: Treatment suggestions included surgical debridement, systemic antifungal therapy and often amputation of affected lower limbs [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Case reports with limb salvage in well vascularized body regions such as the hand have also been reported [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Amputation was performed in more instances than not and seemed a possibility for our patient as well, considering the invasiveness of mucormycosis with bone and soft tissue destruction leading to high mortality [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAfter diagnosing FRI in our patient, we initiated anti-infective therapy, including surgical debridement, removal of foreign implants, and adjuvant systemic antimycotics with oral posaconazole. Due to our patient's immunocompetence and lack of medical history, we pursued the concept of limb salvage under close clinical observation. After 6 weeks of unsuccessful eradication of \u003cem\u003eM. velutinosus\u003c/em\u003e with posaconazole, the guidelines of the European Society of Clinical Microbiology and Infectious Diseases recommend escalation to intravenous liposomal AmB for the treatment of invasive fungal infections [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. An earlier escalation may have led to earlier eradication of the infection. However, it is important to note that AmB can lead to serious adverse effects, such as nephrotoxicity [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Due to the absence of acute signs of infection, an escalation was initially waived.\u003c/p\u003e \u003cp\u003eOur therapy also involved the local application of AmB using PMMA spacers to achieve higher antifungal concentrations on site. This method has been proven to be highly effective in treating bacterial infections in cases where poorly vascularized bone is not accessible to systemic intravenous anti-infective therapy [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHyperbaric oxygenation therapy (HBOT) can be considered as an additional therapeutic tool for treating mucormycosis. Data on the effectiveness of HBOT in treating fungal infections is limited and inconsistent. HBOT has been suggested to promote wound healing and inhibit fungal growth, and it has been proposed as an adjunct therapy to antifungal and surgical treatments for rhinocerebral mucormycosis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this case radical debridement of the upper ankle joint combined with antifungal medication, resulted in the eradication of the fungal infection. This procedure resulted in a bone defect of approximately 5 cm. Our interdisciplinary team discussed various reconstruction options, including internal fixation, allograft or autograft bone transplants, external fixation, and soft tissue reconstruction with a free flap. However, due to the high risk of infection relapse, a hexapod fixator was chosen as a reliable external fixation method for complex lower limb injuries [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Limb salvage was ultimately achieved, with a follow-up of 12 months post trauma.\u003c/p\u003e \u003cp\u003eIn the era of standard operating procedures and algorithms, the authors suggest the following approach in immunocompetent patients with mucormycotic FRI: Treatment by an experienced team of surgeons and infectiologists is recommended. Tissue samples should also be examined for fungal pathogens using cultures and histopathology. After pathogen identification and diagnosis of mucormycotic FRI, antifungal treatment with oral posaconazole or, if possible, intravenous liposomal AmB is recommended. Early and complete removal of foreign implants as well as necrotic tissue is inevitable during the debridement of soft tissue and bone. Local antifungal treatment options, such as AmB-infused PMMA spacers, can be utilized. Adjunct HBOT may be considered. Reconstruction of soft tissue and bone can be performed once tissue samples test negative and the ongoing FRI is eliminated.\u003c/p\u003e \u003cp\u003eIn cases of rapid progression of mucormycosis or lack of reconstructive options, the treatment course of limb salvage may be aborted, with amputation available as a fallback.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMultidisciplinary cooperation is crucial for salvaging the lower extremity in cases of mucormycotic FRI. This begins with early histopathological and microbiological examinations, which allow for timely surgical and antifungal treatment. Despite the invasive growth of mucormycetes, it is important to avoid hasty decisions regarding amputation, especially in patients with no comorbidities and an intact immune system. Limb salvage is a viable option in a setting where ongoing clinical reevaluation is possible and immediate surgical intervention is available in case of infection aggravation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funds, grants, or other support was received.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.E. and S.H. wrote the main manuscript text. A.E., V.K. and S.H. prepared the figures. A.E., M.M., T.K., M.P. and S.H. were involved with direct patient contact. A.E., T.K. , V.K. and S.H. performed significant data collection and analysis. A.E., M.P. and S.H. did extensive literature review for treatment course as well as for the manuscript. All authors reviewed the manuscript before submission.\u003c/p\u003e\n\u003ch2\u003eCompeting interests:\u003c/h2\u003e\n\u003cp\u003eThe authors have no competing interests to declare that are relevant to the content of this article.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eConsent to participate and publish:\u003c/h2\u003e\n\u003cp\u003eThe participant has consented to the submission of the case report to the journal.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis 2019; 19: e405\u0026ndash;e421.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkiada A, Rigopoulos D, Larios G, et al. Global epidemiology of cutaneous zygomycosis. Clin Dermatol 2012; 30: 628\u0026ndash;632.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeong W, Keighley C, Wolfe R, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clinical Microbiology and Infection 2019; 25: 26\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhuman H, Voelz K. Innate and Adaptive Immunity to Mucorales. \u003cem\u003eJournal of Fungi\u003c/em\u003e; 3. Epub ahead of print 1 September 2017. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/JOF3030048\u003c/span\u003e\u003cspan address=\"10.3390/JOF3030048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries. Lancet Microbe 2022; 3: e543.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Meo D, Cera G, Ceccarelli G, et al. Candida fracture-related infection: a systematic review. J Bone Jt Infect 2021; 6: 321.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaj-Aldeen SJ, Gamaletsou MN, Rammaert B, et al. Bone and joint infections caused by mucormycetes: A challenging osteoarticular mycosis of the twenty-first century. Med Mycol 2017; 55: 691.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetsemakers WJ, Morgenstern M, McNally MA, et al. Fracture-related infection: A consensus on definition from an international expert group. Injury 2018; 49: 505\u0026ndash;510.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsperges E, Albi G, Truffelli F, et al. Fungal Osteomyelitis: A Systematic Review of Reported Cases. \u003cem\u003eMicroorganisms\u003c/em\u003e; 11. Epub ahead of print 1 July 2023. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/MICROORGANISMS11071828/S1\u003c/span\u003e\u003cspan address=\"10.3390/MICROORGANISMS11071828/S1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoerdt KM, Zolper EG, Starr AG, et al. Cutaneous mucormycosis of the lower extremity leading amputation in two diabetic patients. Arch Plast Surg 2021; 48: 231\u0026ndash;236.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhatt M, Soneja M, Fazal F, et al. Two cases of Osteoarticular Mucor menace: A diagnostic and management conundrum. Drug Discov Ther 2018; 12: 374\u0026ndash;378.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiourin E, Kanack M, Ng W, et al. Mucor Osteomyelitis of the Distal Radius Necessitating Ulnocarpal Fusion. \u003cem\u003eCureus\u003c/em\u003e; 13. Epub ahead of print 20 January 2021. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.7759/CUREUS.12813\u003c/span\u003e\u003cspan address=\"10.7759/CUREUS.12813\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpuehler D, Fuchs J, Hainich J. Mucor osteomyelitis after traumatic forearm amputation in a 38-year-old patient. Case Reports Plast Surg Hand Surg; 10. Epub ahead of print 2023. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/23320885.2023.2259468\u003c/span\u003e\u003cspan address=\"10.1080/23320885.2023.2259468\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCornely OA, Cuenca-Estrella M, Meis JF, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect 2014; 20 Suppl 3: 1\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoo AS, Muhsin SA, Walsh TJ. Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B. Expert Opin Drug Saf 2013; 12: 881\u0026ndash;895.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSabra R, Branch RA. Amphotericin B nephrotoxicity. Drug Saf 1990; 5: 94\u0026ndash;108.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanssen AD, Spangehl MJ. Treatment of the infected hip replacement. Clin Orthop Relat Res 2004; 420: 63\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoseph TN, Chen AL, Di Cesare PE. Use of antibiotic-impregnated cement in total joint arthroplasty. J Am Acad Orthop Surg 2003; 11: 38\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCouch L, Theilen F, Mader JT. Rhinocerebral mucormycosis with cerebral extension successfully treated with adjunctive hyperbaric oxygen therapy. Arch Otolaryngol Head Neck Surg 1988; 114: 791\u0026ndash;794.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerguson BJ, Mitchell TG, Moon R, et al. Adjunctive hyperbaric oxygen for treatment of rhinocerebral mucormycosis. Rev Infect Dis 1988; 10: 551\u0026ndash;559.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarwan Y, Turner J, Senan R, et al. Circular external fixation for revision of failed tibia internal fixation. Eur J Orthop Surg Traumatol. Epub ahead of print 2023. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/S00590-023-03660-5\u003c/span\u003e\u003cspan address=\"10.1007/S00590-023-03660-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"mucor velutinosus, fungal infection, fracture-related infection, amphotericin B, arthrodesis","lastPublishedDoi":"10.21203/rs.3.rs-4300379/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4300379/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e \u003cp\u003eFracture-related infections caused by mucormycosis are rare and potentially fatal. Evidence-based experience with its treatment is limited and surgical management ranges from limb salvage to amputation, with indications not always clear.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 56-year-old woman was admitted after an aircraft accident, sustaining major trauma injuries, including a Gustilo-Anderson type III open ankle joint fracture. Following initial damage control surgery with external fixation, the patient developed a fracture-related infection in the ankle caused by \u003cem\u003eMucor velutinosus\u003c/em\u003e. Despite its invasive growth and tenacity, surgical debridement combined with systemic and local antifungal therapy led to remission in this immunocompetent patient. The ankle arthrodesis achieved bone union with a hexapod fixator 10 months post trauma.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eIn the treatment of invasive mucormycosis, a multidisciplinary approach is necessary. Through apt diagnosis and thorough treatment by experienced surgeons, infectiologists and pathologists successful limb salvage may be attained in patients with an intact immune system and amputation can be prevented.\u003c/p\u003e","manuscriptTitle":"Fracture-related infection of the lower limb caused by Mucor velutinosus: amputation or salvation?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 16:49:14","doi":"10.21203/rs.3.rs-4300379/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c84b19ff-0673-409b-bdfb-8a2b7eea2512","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-02T17:26:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-29 16:49:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4300379","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4300379","identity":"rs-4300379","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}