A rare case of mucormycosis in a diabetic patient: diagnostic challenges and clinical management of mucormycosis hand infection.

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.

Cutaneous mucormycosis with suspected dissemination in a patient with metastatic adrenocortical carcinoma.

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.

From Spores to Solutions: A Comprehensive Narrative Review on Mucormycosis.

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.

Immune and metabolic perturbations in COVID-19-associated pulmonary mucormycosis: A transcriptome analysis of innate immune cells.

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.

Rise of mucormycosis during the COVID-19 pandemic and the challenges faced.

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.

Emergence of Rhino-Orbito-Cerebral Mucormycosis in Peru: Impact of the COVID-19 Pandemic.

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.

Unusual orbital mucormycosis due to pecking injury: clinical characteristics and outcomes of four immunocompetent pediatric patients.

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.

Ibrutinib and tracheal mucormycosis: A case report and systematic review of literature.

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.

Mucormycosis in Human Immunodeficiency Virus-Infected Individuals: A Systematic Review of Case Reports.

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.

Part 1: Mucormycosis: prevalence, risk factors, clinical features, and diagnosis.

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.

Epidemiology of COVID-19-Associated Mucormycosis.

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.

COVID-related mucormycosis mimicking dental infection.

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.

Risk factors for pulmonary mucormycosis in subjects with diabetes mellitus-A case-control study.

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.

Hyphae, pseudohyphae, yeasts, spherules, spores, and more: A review on the morphology and pathology of fungal and oomycete infections in the skin of domestic animals.

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.

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Post-COVID mucormycosis in presentation of periodontal abscess.

COVID-19 pandemic has traumatized deep inside in minds and lives of human beings. Those who have survived are at risk of many post-COVID complications; mucormycosis being one of the most common as well as morbid infections. Mucormycosis is also known as black fungus, it is a life-threatening opportunistic fungal infection. Inoculation occurs by inhalation of spores in nose, paranasal air sinuses and in lungs. Mucormycosis is often associated in patients with compromised immunity and it presents with characteristic black necrotic eschar and necrosis. Disease affecting the facial region possess a challenge because it often disseminates with sino-orbital and cranial involvement at the time of diagnosis. Dental practice occasionally encounters unusual and subtle symptoms with non-pathognomonic clinical signs of several fatal diseases which may pretend like a common oral disease. Hence, the key knowledge to oral and primary care physicians and its precise application is necessary for the early diagnosis of such fatal infections to prevent untoward consequences in this COVID era. This article presents a case of mucormycosis with chief complaint of pain and swelling in right front tooth region, which mimicked as periodontal abscess in a patient, leading to delay in the diagnosis possess greater challenges during the treatment.

Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Unmasking the Deadly Fungus: A Case Report of Rhino-Orbital-Cerebral Mucormycosis in a Diabetic Patient With Unusual Presentation.

Mucormycosis (zygomycosis) is a rare, rapidly progressive fungal infection that is opportunistic and usually affects immunocompromised individuals, most commonly patients with diabetes mellitus. It is a fatal infection that requires high clinical suspicion and early disease identification. The global burden of mucormycosis is unknown as it is a rare disease. However, the burden of mucormycosis is increasing worldwide, with the emergence of new risk factors and causative agents. In the Saudi population, the discovered cases and the overall prevalence were low. Herein, we present a case of mucormycosis infection aiming to illustrate the clinical characteristics and the management strategy, besides adding another case to the literature.

Zygomycosis of the Oral Cavity in a Main Referral Centre in Malaysia: A Case Series (1967-2021)

@#Zygomycosis is a rare opportunistic fungal infection caused by fungi in the phylum Mucoromycota, subphylum Mucoromycotina and order Mucorales. Immunocompromised patients may harbour the disease by inhalation of the spores from the environment into the paranasal sinuses. Rhino-orbital-cerebral is the most common form which extends into the oral cavity, especially to the palate. We present twelve cases of zygomycosis diagnosed in the Stomatology Unit, Institute for Medical Research (IMR), Malaysia. Most of the patients are immunocompromised and presented as the rhino-orbital-cerebral form. Routine haematoxylin and eosin (H&E) staining were used for all cases while selected cases required additional special staining. The characteristic histological features of broad, non-septate, branched, amphophilic fungal hyphae are seen. We aim to report this rare occurrence to contribute to the literature and raise awareness about this condition among clinicians. To date, this is the first compilation of oral zygomycosis cases known to be reported in Malaysia.