Mucormycosis

Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with Rhizopus, Mucor, and Lichtheimia, accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.

Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of fungi belonging to the order Mucorales. These molds exist throughout the environment and generally do not cause serious problems in humans. Mucormycosis mainly affects individuals who are immunocompromised. The clinical manifestations of mucormycosis are wide-ranging; they include sinusitis (pansinusitis, rhino-orbital, or rhino-cerebral) as well as cutaneous, gastrointestinal, pulmonary, and disseminate infections. Many uncertainties remain regarding how to control these infections despite the recent addition of triazoles to the antifungal arsenal for treating this infection. Currently, lipid formulations of amphotericin B have become the standard treatment for mucormycosis due to their efficiency. Moreover, a growing body of data supports the need for surgical excision of infected and/or necrosed tissue whenever practical. In this mini review, the current status of treatment options for mucormycosis and recent studies of novel therapeutic options will be presented.

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment's safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine's safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.

PURPOSE: Mucormycosis is a rapidly progressive angioinvasive fungal infection with limited large-scale outcome data. We aimed to describe the epidemiology, clinical spectrum, treatment strategies, and predictors of outcomes in adult patients with proven mucormycosis in Türkiye. METHODS: We conducted a nationwide, retrospective study of 280 adults diagnosed with proven mucormycosis between 2004 and 2024 across 27 tertiary centers. Case definitions were applied according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clinical characteristics, antifungal management, surgical interventions, and outcomes were systematically analyzed. RESULTS: The median age of the cohort was 60 years, and diabetes mellitus, frequently complicated by ketoacidosis, was the most common underlying condition. Rhino-orbital-cerebral disease represented the predominant clinical form, whereas pulmonary, gastrointestinal, and disseminated presentations were less frequent but carried less favorable prognoses. Liposomal amphotericin B was the main first-line therapy, often combined with surgery, although antifungal treatment was initiated at a median of five days after symptom onset. Ninety-day mortality was 42.1% by Kaplan–Meier estimation (crude 49.3%) and reached 49.3% (crude 55.0%) at 365 days. Crude mortality was lowest in patients who did not undergo surgery; however, this association was not significant in the time-dependent Cox regression analysis, suggesting confounding by baseline severity. Poor outcomes were associated with corticosteroid exposure, prolonged neutropenia, and neurological manifestations, while a history of sinusitis appeared to be associated with improved survival. CONCLUSION: In this multicenter study, survival was mainly determined by host-related factors rather than the choice of antifungal agent. Corticosteroid exposure, prolonged neutropenia, and neurological involvement independently predicted poor outcomes, whereas a prior history of sinusitis was linked to improved survival, likely reflecting earlier diagnosis and intervention. These findings reinforce the need for heightened clinical awareness, rapid recognition, and prompt multidisciplinary management to improve outcomes in patients with mucormycosis.