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Background: Mucormycosis is a deadly invasive fungal infection recently included in the WHO priority pathogen list. Here we sought to describe epidemiological trends of mucormycosis in France, and to evaluate factors associated with mortality. Methods: From 2012 to 2022, we implemented a nationwide prospective surveillance programme for mucormycosis in France, focusing on epidemiology, species, seasonal variations. Factors associated with 3-month mortality were studied by univariable and multivariable logistic regression. Findings: Among 550 cases of mucormycosis, the main underlying conditions were haematological malignancy (HM, 65.1%, 358/550), trauma (8%, 44/550), diabetes (7.5%, 41/550) and solid-organ transplants (6.5%, 36/550). Site of infection was pulmonary in 52.4% (288/550), rhinocerebral in 14.5% (80/550), and cutaneo-articular in 17.1% (94/550). Main species identified were Rhizopus arrhizus (21%, 67/316), Rhizopus microsporus (13.6%, 43/316), Lichtheimia corymbifera and Mucor circinelloides (13.3%, 42/316 each), Rhizomucor pusillus (12%, 38/316), and Lichtheimia ramosa (10.8%, 34/316). We found associations between underlying condition, site of infection, and infecting species, including a previously undescribed triad of trauma, cutaneo-articular localisations, and L. ramosa/M. circinelloides. Diagnostic contribution of Polymerase Chain Reaction (PCR) increased from 16% (4/25) in 2012 to 91% (61/67) in 2022, with more than 50% of diagnoses relying solely on PCR in 2022. We also found seasonal variations with relatively more cases in autumn. Ninety-day mortality was 55.8% (276/495). Independent prognostic factors were age, diagnosis in Intensive Care Unit (ICU), and HM while diagnosis after 2015 (i.e. large implementation of PCR) and surgery were associated with reduced mortality. Interpretation: This study reveals major mucormycosis epidemiological changes in France, with a large predominance of HM patients, and a parallel between PCR multicentre implementation and improved prognosis. We also evidence new associations between species, localisations and risk factors, as well as seasonal variations. Funding: Recurrent financial support from Santé Publique France and Institut Pasteur.

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Background: During the coronavirus disease 2019 (COVD-19) pandemic, the incidence of mucormycosis also increased, especially affecting individuals who have had the COVID-19 infection in the past. Aims: The aim of the study is to assess risk factors and clinical and histopathological features of mucormycosis in post-COVID-19 cases. Methods: This is a retrospective study conducted in a tertiary care COVID-19-dedicated hospital, Dehradun, Uttarakhand, India, over a period of 2 months during the COVID-19 pandemic. All surgical specimens submitted for histopathology with a suspected diagnosis of mucormycosis were included. Histopathology was considered the gold standard. All histopathologically confirmed cases were studied in detail with respect to histopathology, clinico-radiological features, and microbiological results. Results: Of 25 cases with clinical diagnosis of mucormycosis, nine were histopathologically confirmed as mucormycosis. Seven patients had diabetes, while two did not have any co-morbidity. The fungal load was heavy in 50% cases, and the proportion of necrosis was higher with diabetes mellitus, as compared to non-diabetic and non-co-morbidity patients. Angioinvasion (33.3% cases), soft-tissue invasion (44.4%), Splendor-Hoeppli phenomenon (44.4%), and neural invasion (11.1%) were also present. Mixed infection (Mucormycosis and Aspergillus species) was present in three of the cases who also had diabetes. The microbiological investigations were positive in only 55.5% cases. Conclusion: Post-COVID Mucormycosis has fatal outcomes. Early diagnosis and treatment are the key to successful treatment. Early and reliable diagnosis can be offered by histopathological examination.

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Mucormycosis is an opportunistic fungal infection that primarily affects immunocompromised individuals and rarely presents as renal mucormycosis (RM). Diagnosis can be challenging for many physicians. We report a rare case of primary, unilateral RM which triggered diabetic ketoacidosis in a type 2 diabetic patient. The case was later complicated by a bronchopleural fistula and a meropenem-resistant Klebsiella infection. The patient was ultimately treated with surgical intervention, liposomal amphotericin B, and polymyxine E. Early diagnosis and timely treatment of this life-threatening disease and its complications are significant in reducing mortality.

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Sternal osteomyelitis and mediastinitis are rare yet severe complications post-cardiac surgery, often associated with significant morbidity and mortality. Fungal etiologies, particularly those caused by Rhizopus spp., are infrequent but can lead to aggressive infections. Here, we present the case of a 68-year-old male who developed sternal osteomyelitis and mediastinitis caused by Rhizopus spp. two weeks following coronary artery bypass grafting surgery. Debridement and pectoralis flap reconstruction were performed following clinical identification and confirmation with microbiological examinations and a CT scan. Prompt recognition, aggressive surgical intervention, and targeted antifungal therapy were crucial for successful management. This case underscores the importance of considering fungal pathogens, such as Rhizopus, in the differential diagnosis of post-cardiac surgery infections, as well as aggressive treatment to improve outcomes for affected patients.

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During the COVID-19 pandemic, a significant increase in cases of mucormycosis was observed in COVID-19 patients, especially in India, but not exclusively. The presented cases highlight the heterogeneous nature of mucormycosis, emphasizing the importance of recognizing predisposing factors, such as immunosuppression, due to comorbidities or medication. Diagnosing mucormycosis poses a challenge due to nonspecific clinical manifestations, requiring a multidisciplinary approach for accurate diagnosis. Treatment involves a multi-pronged approach centered around the early initiation of antifungal therapy alongside surgical intervention and the management of underlying conditions, with an emphasis on controlling immunosuppression. Understanding the relationship between COVID-19 and predisposing factors for mucormycosis is fundamental for developing prevention and treatment strategies.

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BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

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Mucormycosis hand infection in poorly controlled diabetic presented as rapidly progressive swelling, redness, pain, and necrosis unresponsive to antibiotics. Prompt diagnosis and aggressive surgery, antifungals, and diabetes management were critical, highlighting the need for early recognition and treatment of mucormycosis in diabetics.

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Mucormycosis is a frequently lethal fungal infection that most commonly affects patients with poorly controlled diabetes or other immunosuppressed states. We report the case of a suspected disseminated Rhizopus infection in a patient who was pursuing naturopathic treatment including mud baths for metastatic adrenocortical carcinoma. He was empirically treated with liposomal amphotericin B but opted to stop treatment following multiorgan failure. The patient passed away on the tenth day of his hospital admission.

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Mucormycosis is an infrequent but fatal illness that mainly affects patients with uncontrolled diabetes mellitus, diabetic ketoacidosis, solid and hematologic neoplasms, organ transplantation, chronic steroid intake, prolonged neutropenia, iron overload states, neonatal prematurity, severe malnutrition, and HIV. Many cases were reported across the world recently following the COVID-19 pandemic. Recent research has led to a better understanding of the pathogenesis of the disease, and global guidelines are now available for managing this serious infection. Herein, we comprehensively review the etiological agents, pathogenesis, clinical presentations, diagnosis, and management of mucormycosis.

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BACKGROUND AND OBJECTIVES: The mechanisms underlying COVID-19-associated pulmonary mucormycosis (CAPM) remain unclear. We use a transcriptomic analysis of the innate immune cells to investigate the host immune and metabolic response pathways in patients with CAPM. PATIENTS AND METHODS: We enrolled subjects with CAPM (n = 5), pulmonary mucormycosis (PM) without COVID-19 (n = 5), COVID-19 (without mucormycosis, n = 5), healthy controls (n = 5) without comorbid illness and negative for SARS-CoV-2. Peripheral blood samples from cases were collected before initiating antifungal therapy, and neutrophils and monocytes were isolated. RNA sequencing was performed using Illumina HiSeqX from monocytes and neutrophils. Raw reads were aligned with HISAT-2 pipeline and DESeq2 was used for differential gene expression. Gene ontology (GO) and metabolic pathway analysis were performed using Shiny GO application and R packages (ggplot2, Pathview). RESULTS: The derangement of core immune and metabolic responses in CAPM patients was noted. Pattern recognition receptors, dectin-2, MCL, FcRγ receptors and CLEC-2, were upregulated, but signalling pathways such as JAK-STAT, IL-17 and CARD-9 were downregulated; mTOR and MAP-kinase signalling were elevated in monocytes from CAPM patients. The complement receptors, NETosis, and pro-inflammatory responses, such as S100A8/A9, lipocalin and MMP9, were elevated. The major metabolic pathways of glucose metabolism-glycolysis/gluconeogenesis, pentose phosphate pathway, HIF signalling and iron metabolism-ferroptosis were also upregulated in CAPM. CONCLUSIONS: We identified significant alterations in the metabolic pathways possibly leading to cellular iron overload and a hyperglycaemic state. Immune responses revealed altered recognition, signalling, effector functions and a pro-inflammatory state in monocytes and neutrophils from CAPM patients.

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Introduction Mucormycosis is an invasive fungal infection caused by Mucorales that has been increasingly recognized over the years, particularly during the COVID-19 pandemic. Nevertheless, in Peru, there has been limited research on this disease. This study seeks to provide insights into the demographics, clinical presentations, treatment, and outcomes of patients with mucormycosis, before and during the COVID-19 pandemic. Materials and methods We conducted a retrospective case series by reviewing the medical records of Peruvian patients hospitalized at a referral medical center between 2017 and 2021. The selection criteria included patients aged 18 years or older with clinical features of rhino-orbito-cerebral mucormycosis supported by radiological imaging. We extracted data related to risk factors for mucormycosis infection, clinical presentation, management, and hospitalization. Data analysis was performed using Stata software (StataCorp LLC, College Station, Texas, USA) to compare patient groups before and during the COVID-19 pandemic. Results Nineteen cases met our selection criteria: 11 men and eight women with an average age of 57.6 ± 10.6 years. All 19 patients had type 2 diabetes mellitus as comorbidity, with 13 cases exhibiting uncontrolled diabetes. Six patients presented before the COVID-19 pandemic, while 13 during its course. Within the group of patients diagnosed during the pandemic, nine were diagnosed with SARS-CoV-2 infection. Regarding the site of mucormycosis infection, the paranasal sinuses were predominantly involved. Survival analysis indicated that patients who developed mucormycosis during the COVID-19 pandemic, those with uncontrolled diabetes, or those who did not undergo surgery had lower probabilities of survival. Conclusion Mucormycosis is a rare infection associated with high mortality and morbidity with increased frequency during the COVID-19 pandemic. Early diagnosis, timely administration of antifungal treatment, surgery, and effective management of comorbidities can have life-saving implications. Unfortunately, despite the availability of various diagnostic tests and less toxic antifungal options such as liposomal amphotericin-B, such resources are not accessible in Peru's national hospitals.

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Mucormycosis (previously called zygomycosis) is a diverse group of increasingly recognized and frequently fatal mycotic diseases caused by members of the class zygomycetes. Mucormycosis is around 80 times more common in India, compared to other developed countries, with a frequency of 0.14 cases per 1,000 population. The most frequent causative agent of mucormycosis is the following genera from the Order Mucorales Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea. The major risk factors for the development of mucormycosis are diabetic ketoacidosis, deferoxamine treatment, cancer, solid organ or bone marrow transplantations, prolonged steroid use, extreme malnutrition, and neutropenia. The common clinical forms of mucormycosis are rhino-orbital-cerebral, pulmonary, cutaneous, and gastrointestinal. During the second wave of COVID-19, there was a rapid increase in mucormycosis with more severity than before. Amphotericin B is currently found to be an effective drug as it is found to have a broad-spectrum activity and posaconazole is used as a salvage therapy. Newer triazole isavuconazole is also found effective against mucormycosis. This study aimed to review various studies on the laboratory diagnosis and treatment of mucormycosis.

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Mucormycosis is a serious fungal infection caused by fungi in the order of Mucorales. Orbital mucormycosis occurs more frequently in rhino-orbital, sino-orbital, and rhino-orbito-cerebral forms of the disease, while isolated orbital mucormycosis is much less common. Herein, we present four cases of immunocompetent children who developed primary cutaneous mucormycosis, which subsequently invaded and progressed to orbital mucormycosis following direct traumatic injury caused by pecking from Acridotheres tristis (Common Myna). Given the low prevalence of orbital mucormycosis in healthy children, an unknown source of infection and delayed diagnosis followed by late therapeutic interventions could result in life-threatening conditions and serious sequelae.

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Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved for various hematological malignancies. Invasive aspergillosis is a known complication of ibrutinib, but mucormycosis is rare. We describe the case of a 70-year-old man with mantle cell lymphoma infiltrating the trachea, managed with a tracheobronchial stent and ibrutinib. He had improved one month after treatment, and we removed the airway stent. Four months later, he developed tracheal nodules confirmed to be tracheal mucormycosis and responded to liposomal amphotericin B (3.5 g) followed by posaconazole. After transient improvement, the tracheal lesions recurred, the biopsy showed lymphoma (with no evidence of mucormycosis), and he died. A systematic review of the literature identified 20 additional cases of ibrutinib-associated mucormycosis. Most of the 21 patients included were men (95%), and ibrutinib was the only risk factor in 15.7%. The reported mortality was 31.6% (6/19), attributable to mucormycosis in half the cases.

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Mucormycosis in human immunodeficiency virus (HIV) infection is uncommon; notably, many cases have additional predisposing factors. Whether mucormycosis differs in HIV-affected individuals with and without additional risk factors (e.g., neutropenia, diabetes mellitus, and transplantation) remains unclear. In this systematic review, we identified 94 cases of HIV and mucormycosis classifiable into three groups: (1) HIV with additional risk factors (n = 50), (2) intravenous drug users (IVDU, n = 24), and (3) no other risk factor (n = 19) for mucormycosis. The most common presentation in IVDU was renal (41.7%) and cerebral mucormycosis (39.2%), whereas rhino-orbital mucormycosis (ROM, 4.2%) was uncommon. In the other two groups, ROM was the most common presentation. Rhizopus was the most frequently isolated Mucorales; however, in IVDU, Lichtheimia was the most common. The overall mortality was 53% and not significantly different in the three groups. Mucormycosis in HIV-infected individuals is rare without additional risk factors or IVDU.

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Purpose of the Review: To describe the epidemiology and risk factors for Coronavirus disease-19 (COVID-19)-associated mucormycosis (CAM) based on current published literature. Recent Findings: COVID-19 is associated with an increased risk of secondary infections. Mucormycosis is an uncommon invasive fungal infection that typically affects people with immunocompromising conditions and uncontrolled diabetes. Treatment of mucormycosis is challenging and is associated with high mortality even with standard care. During the second wave of the COVID 19 pandemic, an abnormally high number of CAM cases were seen particularly in India. Several case series have attempted to describe the risk factors for CAM. Summary: A common risk profile identified for CAM includes uncontrolled diabetes and treatment with steroids. COVID-19-induced immune dysregulation as well as some unique pandemic specific risk factors may have played a role.

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INTRODUCTION: Mucormycosis (MCR) is caused by filamentous molds within the Class Zygomycetes and Order Mucorales. Infections can result from inhalation of spores into the nares, oropharynx, or lungs, ingestion of contaminated food or water, or inoculation into disrupted skin or wounds. In developed countries, MCR occurs primarily in severely immunocompromised hosts. In contrast, in developing/low income countries, most cases of MCR occur in persons with poorly controlled diabetes mellitus and some cases in immunocompetent subjects following trauma. Mucormycosis exhibits a propensity to invade blood vessels, leading to thrombosis and infarction of tissue. Mortality rates associated with invasive MCR are high and can exceed 90% with disseminated disease. Mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM); (2) pulmonary; (3) cutaneous; (4) gastrointestinal or renal (5); disseminated; or (6) uncommon (focal) sites. AREAS COVERED: The authors discuss the prevalence, risk factors, and clinical features of mucormycosis. A literature search of mucormycosis was performed via PubMed (up to November 2022), using the key words: invasivefungal infections; mold; mucormycosis;Mucorales; Zyzomyces; Zygomycosis; Rhizopus, diagnosis. EXPERT OPINION: Mucormycosis occurs primarily in severely immunocompromised hosts. Mucormycosis can progress rapidly, and delay in initiating treatment by even a few days worsens outcomes.

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BACKGROUND: Factors associated with pulmonary mucormycosis (PM) among subjects with diabetes mellitus (DM) remain unclear. Following the coronavirus disease (COVID-19)-associated mucormycosis outbreak in India, specific environmental exposures (especially cattle dung exposure) were proposed as possible aetiology. We hypothesized that environmental factors are associated with PM. We compared subjects with DM with (cases) and without PM (controls). METHODS: In this case-control study, for each PM case, we included five unmatched diabetic controls (hospital [n = 2], community [n = 3]) without PM. We collected information on demography, COVID-19 infection, glycated haemoglobin% (HbA1c), the type of house (pucca vs. kutcha) where the participants reside, and other environmental factors. The primary exposure tested was cattle dung exposure (CDE; using cattle dung cakes as fuel or cattle handling). We performed a multivariate logistic regression to explore factors associated with PM and report the association as an adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: We enrolled 39 PM cases and 199 controls (hospital [n = 80], community [n = 119]). CDE (OR 0.68, 95% CI [0.14-3.31]; p = 0.63) was not associated with increased PM in DM. We found male sex (OR 4.07, 95% CI [1.16-14.31]), higher HbA1c (OR 1.51, 95% CI [1.18-16.32]), COVID-19 (OR 28.25, 95% CI [7.02-113.6]) and residence at kutcha house (OR 4.84, 95% CI [1.33-17.52]) associated with PM. CONCLUSION: Cattle dung exposure was not associated with PM in subjects with DM. Instead, male sex, poor glycaemic control, COVID-19 and the type of housing were associated with pulmonary mucormycosis.

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A recent increase in the prevalence of mucormycosis of the head and neck in patients who have recovered from COVID-19 following hospitalization has been reported. A Majority of the cases have been reported from India. Conditions such as diabetes mellitus, use of corticosteroids for other autoimmune conditions, organ transplant, immunosuppression, immunodeficiency, and malignancies especially hematologic ones, are all known risk factors for mucormycosis. Recently, hospitalization for COVID-19 has been added to the list of risk factors for opportunistic mucormycosis infection. This is likely attributable to the high doses and prolonged use of corticosteroids in the treatment of hospitalized COVID-19 patients. Case Description: Two patients with post-COVID-19 associated rhinocerebral mucormycosis presented with profound unexplained dental disease including tooth mobility and dental abscess mimicking periodontal disease. The patients were previously hospitalized for COVID-19 and received prolonged treatment with high doses of corticosteroids. The patients responded well to the surgical debridement with or without antifungal therapy. Conclusion: Oral healthcare providers including oral and maxillofacial surgeons, dentists, dental hygienists, and other dental practitioners can play a vital role in the recognition and early diagnosis of rhinocerebral mucormycosis given the large number of patients with severe COVID-19 infection who have recovered following hospitalization and/or received long-term high doses of immunosuppressive treatment.

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Fungi are among the most common infectious agents affecting the skin of animals. The skin can serve as a port of entry for fungal infections, which can eventually become disseminated. In some regions of the world, oomycetes, such as Pythium and Lagenidium, are also responsible for a significant number of severe cutaneous infections. Histologic evaluation of fungal morphology, including size, shape, septation, branching, and budding characteristics, combined with the distribution of inflammatory infiltrates within different skin layers can potentially identify etiologic agents, guiding selection of antifungals and additional diagnostics. Fungal infections of the skin surface are typically caused by Malassezia and rarely Candida, with opportunistic fungi also capable of colonizing the skin surface, especially when the barrier is broken. Folliculocentric infections, caused by dermatophytes, result in mild to severe inflammation and can occasionally penetrate deep into the skin. A wide range of fungi, including agents of hyalohyphomycosis, phaeohyphomycosis, and dimorphic fungal infections, as well as oomycetes, result in nodular cutaneous and subcutaneous lesions. With the occasional exception of dimorphic fungi, fungal speciation often requires cultures performed on fresh tissues. However, molecular techniques such as pan-fungal polymerase chain reaction on paraffin blocks is becoming an increasingly useful tool to distinguish between cutaneous fungal pathogens. This review focuses on describing the clinical and histologic features of the most common fungal and oomycete infections affecting the skin of animals, divided according to distribution patterns of lesions and fungal or oomycete morphology.

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