Mucormycosis is a highly invasive and rare opportunistic infection caused by mucor fungi, characterized by challenging diagnosis and rapid disease progression. It predominantly affects patients with compromised immune systems due to various reasons, such as kidney failure, long-term use of antibiotics or corticosteroids. We recently successfully treated a pediatric patient with rapidly progressive glomerulonephritis accompanied by severe cutaneous mucormycosis. To our knowledge, this is the first reported case of rapidly progressive glomerulonephritis nephritis accompanied by dermatophytosis in a pediatric patient. In this case, we share our management experience, including special nursing experience. Cutaneous mucormycosis progresses quickly and is difficult to diagnose and treat, especially in children with compromised immune function, warranting high vigilance from clinicians and nursing staff. Early diagnosis and targeted treatment are crucial for improving the prognosis of patients. Therefore, once there is a suspicion of a mucormycosis infection, we recommend the early application of various testing methods such as fungal culture, skin biopsy and genetic testing in order to to promptly confirm the diagnosis.

We report a rare case of pulmonary mucormycosis caused by Rhizopus microsporus, which is rare in patients with chronic obstructive pulmonary disease. Rhizopus microsporus had been reported as the most common etiological agent associated with human infections, except Rhizopus oryzae in some studies.

We described a case of 81-year-old man with pulmonary mucormycosis caused by Rhizopus microsporus but no other apparent risk factors including diabetes. The diagnosis mainly relied on sputum cultures and clinical manifestations. Despite antifungal therapy, his condition worsened, resulting in mortality.

In this case, the patient had no underlying diseases such as diabetes or solid tumors. Clinicians should be aware of routine pathogenic microbiological tests of pulmonary mucormycosis in patients with chronic obstructive pulmonary disease. Early and aggressive treatment can lead to improved prognosis.

Intra-abdominal and gastrointestinal mucormycosis are less frequent than rhino-orbito-cerebral and pulmonary mucormycosis, but highly lethal. Their diagnosis remains challenging due to the non-specific clinical presentation. We collected English-language cases of intra-abdominal and gastrointestinal mucormycosis in non-haematological and non-neonatal patients published up to October 2024. This review analysed the epidemiological, clinical, and therapeutic charts of 290 cases. A proportion of 53.4% were reported from India and the USA. The main predisposing conditions were diabetes, solid organ transplant, ICU, and corticosteroid treatment. The most common site was the stomach (53.8%). Gastrointestinal perforation, skin breakdown, and abdominal wall infection were sources of intra-abdominal localisation. The most common symptoms were abdominal pain, vomiting, and gastrointestinal bleeding. The diagnosis relied on histology (93.8%), mycology with microscopy and culture (38.8%), and molecular methods (9.9%). Mortality (52.9%) was lower when treatment was intravenous amphotericin B, combined or not with surgery. Prompt treatment, essential for a favourable outcome, relies on early suspicion and diagnosis. Gastrointestinal and intra-abdominal mucormycosis should also be suspected in patients admitted in ICU with ventilation/nasogastric tube and corticosteroids and those with abdominal trauma or surgery, presenting abdominal distension, pain, and GI bleeding. Mycological diagnosis including direct examination, culture and Mucorales qPCR on tissue should assist with rapid diagnosis and thus treatment.

Fungal infections present an increasing global health challenge, with a substantial annual mortality rate of 1.6 million deaths each year in certain situations. The emergence of antifungal resistance has further complicated treatment strategies, underscoring the urgent need for novel therapeutic approaches. This review explores recent advances in nanoparticle-based therapies targeting fungal infections, emphasizing their unique potential to enhance drug solubility, bioavailability, and targeted delivery. Nanoparticles offer the ability to penetrate biological barriers, improve drug stability, and act as direct antifungal agents by disrupting fungal cell walls and generating reactive oxygen species. Despite their promising applications, challenges such as potential toxicity, scalability of production, and the need for controlled drug release remain. Future research should focus on optimizing nanoparticle properties, evaluating long-term safety profiles, developing environmentally sustainable synthesis methods, and exploring synergistic approaches with existing antifungal drugs. Nanotechnology offers a transformative opportunity in the management of fungal diseases, paving the way for more effective and targeted treatments.

To illustrate the imaging findings of orbital compartment syndrome (OCS) in patients with orbital mucormycosis and to identify the red flag signs on imaging for prompt diagnosis and timely intervention.

We conducted a retrospective analysis of CT and MRI scans from patients diagnosed with sino-nasal mucormycosis within three months of a confirmed COVID-19 infection. Microbiologically proven cases of mucormycosis were included. Images were analysed for: Route of spread; proptosis; tenting of globe, Retro-orbital fat/extraocular muscle (EOM) nonenhancement; Intra-orbital abscess, superior ophthalmic vein (SOV) thrombosis, stretching/thickening/enhancement/diffusion restriction of optic nerve, orbital coat, and EOM. Descriptive statistics were elaborated in the form of mean/standard deviations for continuous variables and frequencies and percentages for categorical variables.

Out of 138 patients with mucormycosis, 49 had orbital involvement, OCS was present in 16 orbits. The mean age was 48.6 years with M: F of 2.75:1. Adjacent sinuses were involved in all patients. Spread along nerves and nasolacrimal duct was seen in 94% patients. Globe tenting was seen in all and thickening/coat enhancement in 53.3%. Optic nerve (ON) was thickened in 87.5%, diffusion restriction of ON and EOM in 78.5% cases. Non enhancement of retro-orbital fat was seen in 50% and intra-orbital abscess in 62.5% cases.

OCS is a vision-threatening orbital emergency, leading to OIS and permanent blindness, if not managed promptly. Imaging features that warrant immediate clinical/ surgical intervention to avoid permanent loss of vision are distorted globe, posterior tenting of the globe, stretching of the optic nerve, non-enhancement of retro-bulbar fat and extra-ocular muscles (EOMs).

This case report describes a rare occurrence of palatal mucormycosis in a 45-year-old immunocompetent female patient who developed black discoloration of the palate following a tooth extraction. Initial diagnostic investigations and superficial biopsy revealed aspergillosis; however, further postoperative histopathological examination confirmed mucormycosis. Aggressive surgical intervention, including maxillectomy, alveolectomy, and functional endoscopic sinus surgery, combined with targeted antifungal therapy, facilitated successful treatment. The importance of timely diagnosis and comprehensive management in mucormycosis cases, even among immunocompetent patients, is highlighted.

The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to create a guideline focusing on non-Aspergillus invasive molds, which are uncommon yet lethal invasive fungal diseases in the peri-hematopoietic cell transplant (HCT) period. We used a compendium-style approach by dissecting this broad, heterogeneous, and highly complex topic into a series of standalone frequently asked questions (FAQs) and tables. Adult and pediatric infectious diseases and HCT content experts developed, then answered FAQs, and finalized topics with harmonized recommendations. All the evidence for non-Aspergillus invasive mold infection is non-RCT and mostly level III, therefore there are no recommendation grades, and instead key references are provided. Through this format, this "8th" topic in the series focuses on the relevant risk factors, diagnostic considerations, prophylaxis, and treatment approaches relevant to rare mold infections in the pre- and post-transplant periods.

Invasive fungal infection (IFI) due to moulds other than Aspergillus are a significant cause of morbidity and mortality. Non-Aspergillus mould (NAM) infections appear to be on the increase due to an ever-expanding population of immunocompromised hosts. In this review, Mucorales, Scedosporium species, Lomentospora prolificans and Fusarium species are examined in detail, and the microbiology, risk factors, diagnosis and treatment of emerging NAMs such as Paecilomyces variotti, Purpureocillium lilacinum and Rasamsonia are summarized. The challenges in diagnosis are emphasized and the emerging importance of molecular methods is discussed. Treatment of IFI due to NAMs is a multi-pronged and multi-disciplinary approach. Surgery, correction of underlying risk factors, and augmentation of the host immune response are as important as antifungal therapy. Many of these NAMs are intrinsically resistant to the currently licensed antifungal agents, so selection of therapy needs to be guided by susceptibility testing. There are new antifungal agents in development, and these have the potential to improve the efficacy and safety of antifungal treatment in the future. Ongoing research is required to fully delineate the epidemiology of NAM infections, and to develop better diagnostic tools and treatments so that outcomes from these infections can continue to improve.

Mucormycosis is a severe, opportunistic infection caused by Mucorales, a taxonomical group of thermotolerant fungi primarily affecting the immunocompromised. Intra-abdominal involvement in mucormycosis is a rare entity, particularly in immunocompetent individuals. We present a fatal case of gallbladder and renal mucormycosis in an immunocompetent female, leading to septic shock and death. The diagnosis was confirmed via histopathology following cholecystectomy for suspected gangrenous cholecystitis and open right nephrectomy due to kidney infarction. Quantitative polymerase chain reaction of the tissue identified the presence of Apophysomyces ossiformis. The clinical picture was confounded by ongoing sepsis due to a Klebsiella pneumoniae-infected retroperitoneal hematoma, non-specific imaging findings, and the absence of traditional risk factors for mucormycosis, leading to a delayed diagnosis. Despite surgical debridement, initiation of liposomal amphotericin B with posaconazole, and aggressive treatment in the intensive care unit, the patient succumbed to complications of mucormycosis. Despite adequate antibiotic coverage, this case underscores the importance of considering Mucorales infection in otherwise immunocompetent patients with a deteriorating clinical condition. Early diagnosis and appropriate intervention are essential in enhancing mucormycosis survivability, though mortality rates remain high in severe cases.

Mucormycosis is an aggressive and frequently lethal disease. Most patients with mucormycosis have poorly controlled diabetes mellitus and rhino-orbito-cerebral disease. Patients with hematologic malignancy and transplant recipients mostly present with rhino-orbito-cerebral or pulmonary disease. Prompt recognition of clinical symptoms and radiographic features of mucormycosis is required to establish timely diagnosis and initiate targeted therapy. Diagnosis is, historically, made by direct microscopy, culture, and pathology of biopsy tissue, but molecular methods are increasingly playing a role in establishing an earlier diagnosis. Treatment is multidisciplinary, involving early surgical intervention, antifungal therapy, and correction of underlying immune compromising risk factors when possible.

Mucormycosis is an invasive infection caused by fungi of the order Mucorales, typically affecting immunocompromised individuals, and rarely involving the gastrointestinal tract. We report two cases of gastrointestinal mucormycosis by Mucor indicus: a 77-year-old woman with a gastric ulcer and a 25-year-old man with liver lesions. Both were treated with surgery and liposomal amphotericin B; only one survived. Recognizing gastrointestinal mucormycosis in the correct clinical context is essential and requires timely surgical and antifungal treatment. 2012 Elsevier Ltd. All rights reserved.

Isavuconazole has been used to treat invasive fungal infections, however, it is unclear whether the efficacy of isavuconazole is superior to that of voriconazole. The purpose of this meta-analysis was to assess the efficacy and safety of isavuconazole compared to voriconazole in treating invasive fungal infections.

Electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched to identify relevant studies. Studies evaluating the effect of isavuconazole in the treatment of patients with invasive fungal infections were included. Pooled rates of overall response, all-cause mortality, drug-related adverse events (AEs), and discontinuation due to drug-related AEs were calculated.

Seven studies involving 890 patients were included. Meta-analysis showed that there was no significant difference between isavuconazole and voriconazole in overall response (risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.83 to 1.25, p = 0.86) and all-cause mortality (RR: 0.95, 95% CI: 0.78 to 1.16, p = 0.61). However, isavuconazole had a significantly lower incidence of drug-related AEs (RR: 0.70, 95% CI: 0.61 to 0.81, p < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs need further valiadation, but the results of other outcomes were conclusive.  < 0.001) and discontinuation due to drug-related AEs (RR: 0.56, 95% CI: 0.39 to 0.82, p = 0.003) compared with voriconazole. Trial sequential analysis (TSA) confirmed that the difference between isavuconazole and voriconazole in discontinuation due to drug-related AEs needs further validation, but the results of other outcomes were conclusive.

Our findings support the use of isavuconazole as the primary therapy for invasive fungal infections. More research is needed to compare the discontinuation rates of isavuconazole and voriconazole.

Molds are persistent and harmful but receive far less research attention compared with pathogenic bacteria. With the increase in microbial resistance to single-chain surfactant antimicrobial agents, it is crucial to investigate how surfactant structures affect the antimicrobial activity of surfactants. Here, we have studied the antimold efficacy of a series of oligomeric cationic quaternary ammonium surfactants at varying oligomerization levels with or without dynamic covalent imine bonds. Four common molds are chosen as representatives: A. niger, T. viride, C. globosum, and P. funiculosum. The minimum fungicidal concentration (MFC) results indicate that the dynamic covalent surfactants in solution display stronger antimold activity than the surfactants of the same oligomerization degree without imine bonds, and the antimold activity decreases as the oligomerization degree increases. The superior fungicidal efficacy of imine-based surfactants in solution is attributed to their longer hydrophobic chains and benzene rings, which enhance the interactions with mold membranes, causing perforation and membrane disruption. Nonetheless, the higher oligomerization degree reduces antimold effectiveness due to the formation of overly stable aggregates, which lower the concentration of free molecular monomers released from aggregates and may accumulate on mold spore membranes. However, on fabric surfaces, the surfactants with a higher oligomerization degree show stronger antimold performance. The multiple hydrophobic chains and cationic headgroups result in greater surfactant adsorption and stronger antimildew activity. Moreover, the reversibility of the imine-based surfactants plays a significant role in reducing the likelihood of resistance. This work is helpful to construct antimicrobial agents with broad-spectrum activity and a weak resistance potential.

Effect of serum ferritin on severity of coronavirus disease 2019 (COVID-19)-associated rhino-orbito-cerebral mucormycosis.

To study the association between increased serum ferritin and severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis.

A cross-sectional study.

Hundred ( n ) out of 155 treatment-naive patients of COVID-19 infection presenting with the signs and symptoms of rhino-orbito-cerebral mucormycosis were enrolled in study. Based on the classification proposed by Honavar, the study patients were classified into four stages: Stage 1: involvement of the nasal mucosa ( n = 11), Stage 2: involvement of paranasal sinuses ( n = 14), Stage 3: involvement of the orbit ( n = 37), Stage 4: involvement of the central nervous system ( n = 38). Stage 3 was further divided into four substages: 3a: nasolacrimal duct, medial orbit, vision unaffected ( n = 4); 3b: diffuse orbital involvement (>1 quadrant or >2 structures), vision unaffected ( n = 15); 3c: central retinal artery occlusion or ophthalmic artery occlusion, superior ophthalmic vein thrombosis, involvement of superior orbital fissure, inferior orbital fissure, orbital apex, diminution or loss of vision ( n = 13); 3d: bilateral orbital involvement ( n = 5). Fasting blood sugar (FBS), postprandial blood sugar (PPBS), and inflammatory markers (serum ferritin, interleukin-6, C-reactive protein, and D-dimer) were assessed. Serum level of ferritin was analyzed by using chemiluminescence immunoassay method.

Mean FBS (mg/dl) was 165.03 ± 70.43 for stage 1, 185.67 ± 64.82 for stage 2, 159.05 ± 68.60 for stage 3, and 158.20 ± 62.05 for stage 4. Mean PPBS (mg/dl) was 238.70 ± 141.29 for stage 1, 252 ± 103.69 for stage 2, 257.09 ± 103.48 for stage 3, and 229.53 ± 76.81 for stage 4. Mean serum ferritin (μg/l) was 302.67 ± 266.95 in stage 1, 444.19 ± 116.36 in stage 2, 504.85 ± 205.99 in stage 3, and 825.95 ± 777.30 in stage 4. A statistically significant increase in serum ferritin levels with severity of disease ( P = 0.005) was noted. Similar trend was observed in substages of stage 3. Pearson correlation analysis showed a positive correlation between serum ferritin and severity of disease ( P = 0.0007).

Increased serum ferritin was significantly independently associated with severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis.

Aim: To assess the cost-effectiveness of treating invasive aspergillosis with isavuconazole, posaconazole and voriconazole in China.Materials & methods: A cost-consequence analysis (CCA) was conducted, considering both healthcare system and patient out-of-pocket perspectives. We considered the costs of medications, diagnostics and hospitalization and the consequences of mortality, response rate and adverse events.Results: From the healthcare system perspective, compared with voriconazole, isavuconazole saved 967.39 Chinese Yuan (CNY) and posaconazole saved 8624.82 CNY. From the patient out-of-pocket perspective, compared with voriconazole, isavuconazole saved 1056.00 CNY, posaconazole increased 3153.83 CNY. The CCA demonstrated that isavuconazole exhibited higher medical costs but lower out-of-pocket costs compared with posaconazole, while there were no significant differences in consequences.Conclusion: Isavuconazole is potentially the most economical option.

We present the case of a 60-year-old immunocompromised man who presented with two pruritic pink-red indurated nodules with overlying scale and focal areas of ulceration on his left dorsal and left medial forearm, which evolved over a 2-month period. The pathology showed numerous fungal hyphae present that were pauci-septate with various branched angles and variable hyphal thickness. Fungal cultures grew Rhizopus species and a universal fungal PCR detected the Rhizopus oryzae complex. Based on the clinicopathologic correlation, the diagnosis of cutaneous mucormycosis was made. Cutaneous mucormycosis is an aggressive fungal infection of the Mucorales family occurring after the inoculation of fungal spores in disrupted skin. It usually presents as a necrotic eschar but can also present as cellulitis that evolves into a necrotic ulcer. A prompt diagnosis is critical for the effective management of cutaneous mucormycosis. The treatment includes an immediate systemic treatment with amphotericin B and a surgical debridement of the necrotic regions. Given the wide range of presenting symptoms, clinical suspicion for this emergent condition must remain high in immunocompromised and diabetic patients.

This report describes a case of gastric mucormycosis in a young Ragdoll cat with a 5-day history of vomiting. Physical examination detected mild dehydration and tenderness was elicited on abdominal palpation. The results of blood work-up and radiographic study were unremarkable; however, abdominal ultrasonographic examination revealed multiple hyperechoic neoformations at the level of the pyloric antrum, which were confirmed on endoscopic examination. Non-septate hyphae of irregular diameter with a branched appearance were observed on cytology, and histological examination revealed severe diffuse necrotising and granulomatous gastritis with the presence of intralesional fungal hyphae indicative of mucormycosis, which was confirmed by PCR tests. Antifungal therapy with ketoconazole in addition to supportive treatment temporarily improved the clinical condition. Lethargy, fever and abdominal effusion developed in the following days. Cytological examination of abdominal fluid was compatible with septic peritonitis and, given the severity of the condition, euthanasia was opted by the owners. Post-mortem examination confirmed septic peritonitis resulting from perforation of the gastric wall at one of the neoformations of the pyloric antrum.

To the authors' knowledge, this is the first reported case of gastric mucormycosis in a cat. Previous literature includes a case of mucormycosis in a Persian cat affecting only the duodenum. In both the Persian cat and the cat described here, gastrointestinal mucormycosis disease progressed rapidly and was fatal.

The healthcare system has been greatly affected by the COVID-19 pandemic, resulting in an increase in secondary and co-infections among patients. Factors like pulmonary damage and weakened immune systems make patients more susceptible to fungal infections. Mucormycosis, an opportunistic fungal infection, prospers in environments with limited oxygen, and elevated glucose levels due to conditions such as diabetes and steroid use, as well as in acidic environments from metabolic acidosis and diabetic ketoacidosis, where it demonstrates heightened germination ability. Recognizing these complications is critical to minimize harm to patients. The insights gained from this review can improve our understanding of how fungal infections develop in connection to COVID-19, leading to better predictive algorithms, tailored care plans, enhanced antifungal treatments, quicker diagnostics, and improved management strategies.

Rhinocerebral mucormycosis (RM) is a rare and severe condition caused by filamentous fungi, characterized by infection of the nose, paranasal sinuses, and brain. It is the most common and fatal clinical form of mucormycosis, accounting for 50 % of reported cases. RM is seldom reported during the postpartum period. This case report presents a rare instance of RM following childbirth and reviews the most recent literature, highlighting the limited cases documented globally and even fewer within Africa. The aim is to contribute to the existing body of knowledge and provide guidance for clinicians managing similar cases. Notably, this is the first case report to describe this rare condition postpartum in Sub-Saharan Africa, specifically in Tanzania.

In this case report from Northern Tanzania, we report a patient who was diagnosed with rhinocerebral mucormycosis following spontaneous normal delivery. A 34-year- old female presenting with a history of severe headache for 3 weeks, associated with blurry vision and later on completely loss of vision, dizziness and generalized body weakness. A Computed tomography scan (CT) of the head revealed a hypodense lesion of the frontal lobe with an extension compressing the optic chiasm. Magnetic Resonance Imaging (MRI) of the brain revealed hyperintensities in the frontal lobe, thalamus, periorbital regions and nasal sinuses. Treatment was stopped due to an acute kidney injury and the patient self-discharged against medical advice. Since, the patient has not returned for follow up.

In this report, we discuss the rarity of this condition, the literature surrounding similar reports, and the many challenges that arise in the management of rhinocerebral mucormycosis especially in limited resource settings. Currently, reports in the literature are limited. A greater evidence base is required to support the development of effective treatments which would further improve patient outcomes.

Rhinocerebral mucormycosis is potentially fatal disease which progresses rapidly. Early detection and prompt treatment are critical for survival. Antifungal therapy in combination with intensive surgical debridement facilitates improved outcomes for patients. The incidence of rhinocerebral mucormycosis cases in Tanzania has not been studied extensively. More studies are required with specific focus on patients with high risk underlying conditions such diabetes, and hematological malignancies.

Mucormycosis, is a rare yet potentially life-threatening fungal infection common in immunocompromised patients. Despite optimal care, mucormycosis in haemato-oncological patients often results in poor outcomes. This case series details the presentations and unique challenges faced during the management of patients with acute myeloid leukemia who developed rhino-cerebral mucormycosis.

We present three cases of rhino-cerebral mucormycosis in patients with acute myeloid leukemia: two females aged 35 and 29, and one male aged 42. Symptoms manifested during chemotherapy induction, with all patients experiencing symptoms suggestive of rhino, orbital, or cerebral infection in a background of severe neutropenia (ANC < 0.5). Nasal endoscopy revealed necrotic tissue in all cases, with contrast-enhanced computer tomography (CECT) confirming invasive fungal infection. Rhizopus species were isolated in cultures from the two female patients, and histopathological evidence of fungal invasion was noted in one. Prompt treatment with liposomal Amphotericin B combined with surgical debridement with functional endoscopic sinus surgery (FESS) and treatment of neutropenic sepsis resulted in the survival of two patients, though one succumbed during treatment.

This case series highlights the importance of early clinical suspicion and treatment of mucormycosis in hematological malignancies. Due to mild and atypical presentations and lack of confirmation by microbiological and histological methods, a multifaceted diagnostic approach combining clinical, laboratory, and imaging modalities is essential. A multidisciplinary treatment approach with the management of concomitant complications like neutropenic sepsis is crucial for better outcomes.

Mucormycosis is considered a rare but highly lethal fungal infection, often occurring in patients with poorly controlled diabetes or immunosuppression. Pulmonary mucormycosis progresses rapidly and is often associated with pulmonary infarction and hemoptysis. In this case report, we presented a young, immunocompetent female patient with newly diagnosed diabetes who was diagnosed early with Rhizopus delemar infection through metagenomic next-generation sequencing. Despite early diagnosis, the infection progressed rapidly, invading the tracheal cartilage and upper mediastinal soft tissue, ultimately leading to the patient's unfortunate demise.

This review aims to summarize the epidemiology, etiology, pathogenesis, clinical manifestations, and current diagnostic and therapeutic approaches for mucormycosis. The goal is to improve understanding of mucormycosis and promote early diagnosis and treatment to reduce mortality.

A comprehensive literature review was conducted, focusing on recent studies and data on mucormycosis. The review includes an analysis of the disease's epidemiology, etiology, and pathogenesis, as well as current diagnostic techniques and therapeutic strategies.

Mucormycosis is increasingly prevalent due to the growing immunocompromised population, the COVID-19 pandemic, and advances in detection methods. The pathogenesis is closely associated with the host immune status, serum-free iron levels, and the virulence of Mucorales. However, the absence of typical clinical manifestations complicates diagnosis, leading to missed or delayed diagnoses and higher mortality.

An enhanced understanding of the epidemiology, pathogenesis, and clinical presentation of mucormycosis, along with the adoption of improved diagnostic and therapeutic approaches, is essential for reducing mortality rates associated with this opportunistic fungal infection. Early diagnosis and prompt treatment are critical to improving patient outcomes.

This study investigates the differential impact of fecal fungal microbiota on the pathogenesis of alcohol-associated liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD). We aim to delineate distinct microbial patterns across various stages of each disease.

We conducted fungal internal transcribed spacer 2 (ITS2) sequencing analysis on fecal samples from 48 ALD patients, 55 MAFLD patients, and 64 healthy controls (HCs).

Distinct fungal microbiota profiles were significantly identified between the ALD and MAFLD patients. In the ALD group, genera such as Trichosporon, Davidiella and Asterotremella along with species like Trichosporon unclassified and Davidiella unclassified were elevated compared to those in the MAFLD group. Conversely, Fungi unclassified, Rhizopus, Periconia, and Candida albicans were more prevalent in MAFLD patients. A specific fungal signature comprising Asterotremella_pseudolonga, Malassezia_restricta and Malassezia, was notably effective in differentiating ALD from MAFLD, achieving an area under the curve (AUC) of 0.94. Periconia and Periconia byssoides were more abundant in non-obese MAFLD patients compared to obese MAFLD and HCs. Rhizopus microsporus var. chinensis and var. rhizopodiformis, along with Pleosporales unclassified, were predominantly found in MAFLD patients with moderate to severe hepatic steatosis (HS). The genera Pleosporales_unclassified and the species Candida_albicans were markedly elevated in ALC patients when contrasted with AFL or HCs.

This investigation introduces a novel fungal signature that successfully differentiates between ALD and MAFLD, underscoring Pleosporales unclassified, as biomarkers for disease progression in ALD and MAFLD. The findings also suggest a significant role for Periconia in the progression of non-obese MAFLD.

A woman in her 30s with type 2 diabetes and morbid obesity presented with flu-like symptoms, persistent cough and mild dyspnoea, unresponsive to pneumonia treatment. Diagnosed with acute myeloid leukaemia, she was started on induction chemotherapy. Despite prophylactic antifungal and antibacterial therapy, she developed a fever, a right upper lobe opacity and a complete airway obstruction by a large endobronchial mass in the right main stem. Bronchoscopy with biopsy and PCR confirmed mucormycosis. Although a combined antifungal regimen was started promptly, her condition worsened, leading to acute respiratory distress syndrome, tracheo-pleural fistulas and extensive necrotic mucosa in the airways. Surgical intervention was not feasible, and she was transitioned to hospice. Complete central airway obstruction and trachea-pleural fistula are rare manifestations of pulmonary mucormycosis. We conduct a literature review of endobronchial mucormycosis to highlight the importance of early recognition and a multimodal treatment approach to improve outcomes.

Mucormycosis is an invasive fungal infection, caused by fungi of the order Mucorales, and it is associated with high morbidity and mortality. The epidemiology of mucormycosis is evolving. The incidence, underlying risk factors, clinical presentation, as well as the responsible mucoralean agents, vary by geographic region. The estimated incidence in developed countries ranges from less than 0.06 to 0.3 cases per 100,000 population per year, while in India, it reaches approximately 14 cases per 100,000 population per year, which is about 80 times higher. In European countries the estimated incidence ranges from less than 0.04 to 0.12 per 100,000 population per year. Diabetes mellitus (DM) is the leading underlying disease globally. In Europe, hematological malignancies are the most common risk factor for mucormycosis, while in Asia diabetes predominates. The rhino-cerebral form of mucormycosis is most commonly seen in patients with DM, whereas pulmonary mucormycosis in patients with hematological malignancies and transplants. The most common species globally is Rhizopus arrhizus, whereas new emerging species only occasionally cause infection in Europe. However, vigilance is required, as they may raise concerns-especially in light of climate change- due to their potential to cause serious infections in both immunocompetent and immunosuppressed individuals.

Mucormycosis is a rare, severe fungal infection mainly affecting immunocompromised individuals. Because of limited data on its epidemiology in Oman, we present this national, multicentric, retrospective review that includes all cases of proven mucormycosis between 2006 and 2022 in Oman. There were 51 cases of mucormycosis reported in Oman. The annual incidence of mucormycosis was 0.38-0.69 cases per million population before COVID-19. During the pandemic, the incidence rose significantly to 1.76 in 2020, 5.31 in 2021, then decreased to 0.87 per million population in 2022. Diabetes was observed in 82.4% (n = 42) of the cases, COVID-19 in 47.1% (n = 24), and other chronic diseases in 72.6%. The use of steroids was reported in 33.3% (n = 17) and many patients (64.7%, n = 33) had multiple risk factors. The overall mortality rate was 41.2% (n = 21) and most deaths occurred within a month of diagnosis. Mortality rate among patients diagnosed with COVID-19 was 58.3% (14/24). Survival analysis showed a statistically significant association between COVID-19 status and patient survival (p = 0.024). Annual incidence of mucormycosis in Oman rose during the pandemic. This study highlights the epidemiological features of mucormycosis and emphasizes the importance of its inclusion in the national notifiable communicable diseases priority list as well as the importance of enhancing diagnostic capacities to detect and improve patient outcomes.

With increasing use of broad-spectrum antibiotics, advances in organ and stem-cell transplant therapy, and the continued diabetes mellitus II epidemic, as well as other risk factors, reports of fungal infections of the CNS have been increasing. The most lethal subset is the angioinvasive fungal infection. Aspergillus fumigatus, Mucor, and Fusarium tend to affect immunocompromised individuals depending on their risk factors. Exserohilum rostratum and Cladophialaphora species tend to infect immunocompetent individuals. Early diagnosis and treatment are imperative for improved outcomes and reduced morbidity and mortality. Clinical presentation is often nonspecific, while neuroimaging can be helpful for accurate diagnosis. CT of the head and/or the maxillofacial structures is the primary imaging modality. Once the infection begins to proliferate, areas of vasogenic and cytotoxic edema, with regional mass effect and shift of the midline structures may be seen. These findings, however, are often nonspecific and may also be seen in underlying neoplasm, inflammatory processes, and other intracranial infections. Characteristic findings on T1, T2, diffusion-weighted imaging (DWI), and gradient echo sequences (GRE) may help to further narrow the differential diagnoses. We present a review of neuroimaging findings that will aid the neuroradiologist in distinguishing intracranial angioinvasive fungal infections and lead to improved patient outcomes.

We report a case of fulminant Mucorales fungemia in a heavily immunosuppressed cancer patient with hemophagocytic lymphohistiocytosis following CD70-targeted chimeric antigen receptor T-cell therapy. Although rare, Mucorales can cause true fungemia in a broad spectrum of hosts, with a range of manifestations from isolated fungemia to fungemia being part of widely disseminated, high-burden infection.

Cutaneous mucormycosis is a rare fungal infection marked by skin abscesses, swelling, necrosis, dry ulcers, and eschars. Though less fatal compared to other mucormycosis forms, delayed diagnosis and treatment in immunocompromised patients can cause the infection to spread to vital organs, becoming life-threatening. We report a case of lower extremity cutaneous mucormycosis secondary to acute myeloid leukemia, successfully managed with sustained surgical debridement and short-term oral posaconazole. This case highlights the effectiveness of surgical debridement and the potential for short-course antifungal therapy in managing cutaneous mucormycosis.

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging. Therefore, we reviewed 44 consecutive HM patients with probable/proven IPM at MD Anderson Cancer Center in 2000-2020 who had concurrent CCT and CXR studies performed. All 44 patients had abnormal CCTs and 39 (89%) had anormal CXR findings at IPM diagnosis. However, only 26 patients (59%) showed CCT-matching IPM-suspicious lesions on CXR. Acute Physiology and Chronic Health Evaluation II score > 18 at IPM diagnosis and breakthrough infection to Mucorales-active antifungals were the only independent risk factors for 42-day and/or 84-day mortality. Absence of neutropenia at IPM diagnosis, neutrophil recovery in neutropenic patients, and surgical revision of mucormycosis lesions were protective factors. Although not reaching significance on multivariable analysis, visualization of CCT-matching lesions on CXR was associated with significantly increased 84-day mortality (log-rank test, p = 0.033), possibly as a surrogate of extensive lesions and tissue necrosis. This observation supports the exploration of radiologic lesion kinetics as a prognostic staging tool in IPM 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.

A 57-year old man with uncontrolled diabetes presented with features suggestive of chronic meningitis. Cerebrospinal fluid (CSF) analysis revealed a polymorphonuclear pleocytosis with low glucose and high protein levels in the CSF. Bacterial and fungal cultures and tests for M. tuberculosis were negative. MRI spine showed leptomeningeal enhancement. On ruling out other causes, fungal meningitis was considered. The patient developed paraparesis in the hospital. MRI showed peripherally enhancing subdural lesion with dorsal cord involvement at the level of D4 and D5 vertebrae. On laminectomy and exploration, an intradural extramedullary abscess and a granuloma were noticed at T4--T5 spinal levels causing compression of the cord below. Histopathological examination of the lesions revealed acute on chronic inflammatory infiltrates interspersed by broad, aseptate, ribbon-like fungal elements highlighted by PAS stain, diagnostic of mucormycosis. Intravenous amphotericin B and oral posaconazole were administered for more than 8 weeks. On follow-up, he had complete neurological recovery without sequelae.

Mucormycosis is a concerning invasive fungal infection with difficult diagnosis, high mortality rates, and limited treatment options. Iron availability is crucial for fungal growth that causes this disease. This study aimed to computationally target iron uptake proteins in Rhizopus arrhizus, Lichtheimia corymbifera, and Mucor circinelloides to identify inhibitors, thereby halting fungal growth and intervening in mucormycosis pathogenesis. Seven important iron uptake proteins were identified, modeled, and validated using Ramachandran plots. An in-house antifungal library of ~ 15,401 compounds was screened in molecular docking studies with these proteins. The best small molecule-protein complexes were simulated at 100 ns using Maestro, Schrodinger. Toxicity predictions suggested all six molecules, identified as the best binding compounds to seven proteins, belonged to lower toxicity levels per GHS classification. A molecular mechanics GBSA study for all seven complexes indicated low standard deviations after calculating free binding energies every 10 ns of the 100 ns trajectory. Density functional theory via quantum mechanics approaches highlighted the HOMO, LUMO, and other properties of the six best-bound molecules, revealing their binding capabilities and behaviour. This study sheds light on the molecular mechanisms and protein-ligand interactions, providing a multi-dimensional view towards the use of FDBD01920, FDBD01923, and FDBD01848 as stable antifungal ligands.

The online version contains supplementary material available at 10.1007/s40203-024-00264-7.

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients.

This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales.

Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents.

Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US.

We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period.

All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022.

Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality.

Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period.

Rhino-orbital-cerebral mucormycosis is an opportunistic infection caused by fungus species Rhizopus and Mucor. Early recognition and aggressive management is crucial for favorable outcomes. A delay in diagnosis and treatment is fatal.

A 32-year-old female presented with high-grade fever, right-sided facial deviation associated with facial swelling, and inability to move her left eye for 10 days. Biopsy from the left nasal cavity showed fibrinoid material, edema, and sheets of neutrophilic infiltrate while KOH preparation of nasal scrapping showed aseptate hyphae with obtuse-angled branching. Amphotericin B, oral posaconazole, and antibiotics were started with exploration and debridement of the affected tissue. The patient recovered well and was discharged.

Immunocompromised people are primarily affected by mucormycosis, a serious fungal illness. Inhaling fungal spores, especially those of the Rhizopus and Mucor species, is the usual cause. Rhinocerebral mucormycosis (ROCM), the most common type, increased during COVID-19 pandemic, frequently as a result of hyperglycemia brought on by steroids. Angioinvasion and tissue necrosis are pathogenesis-related processes that are made worse by diabetes and the overuse of glucocorticoids. Histopathology, culture, and imaging are used in the diagnosis. Surgery and antifungal drugs like Amphotericin B are used in treatment. Early intervention and interdisciplinary care, including hyperbaric oxygen therapy, are critical for survival. Results deteriorate with postponed therapy, underscoring the urgency of prompt action.

Mucormycosis should be kept in mind while formulating differential diagnosis of infective pathology in immunocompromised patients. Early diagnosis and treatment are important in improving patient prognosis in rhino-orbital-cerebral mucormycosis.

Patients diagnosed with COVID-19 associated mucormycosis were followed up for 6 months to study the clinical profile, readmissions, long-term treatment outcome and the mortality rate.

Among 37 patients with COVID-19 associated mucormycosis, the mortality rate was 33.3 %, 42.9% and 100 % among patients with mild, moderate and severe COVID-19 infection. One month after discharge, among the 20 patients who survived, 10 (50 %) patients had worsening symptoms and required readmission. Nine patients required readmission for amphotericin and 1 patient was admitted for surgical intervention. On follow-up at 1 month, 30 % (6/20) patients became asymptomatic. However, at 3 months, 45 % (9/20) of the patients were asymptomatic. At 6 months of follow-up, 80 % (16/20) were asymptomatic. At 6 months, one each had residual abnormalities like visual loss in one eye, visual field deficit, change in voice and residual weakness of the limbs along with cranial nerve paresis.

The follow-up study revealed that a significant number of patients required readmission within the first month, but most of the patients became asymptomatic by 6 months. The readmission rate was higher in patients who received a shorter duration of amphotericin.

Mucormycosis, a life-threatening fungal infection that primarily affects immunocompromised individuals.The protein family commonly observed in the fugus responsible for causing Mucormycosis. The attachment of spores to host cells surface, facilitated by a protein CotH, is a critical step for the invasion and progression of the disease. Therefore, CotH inhibitors have emerged as a promising therapeutic strategy for treating mucormycosis.This study presents a novel therapeutic target and ligand for controlling the growth of Mucorales. First, to identify potential CotH inhibitors, we surveyed a library antifungal compounds elaborated in AYUSearch database. Next, using machine learning-based algorithms we screend 20 potentials ligands, followed by structure-based molecular modelling and molecular trajectory analysis to identify the three most promising chemical constituents. In-vitro tube assays on selected Mucorales determined the minimum inhibitory concentrations (MIC) for screened chemotypes. The MIC assay revealed that Bacoside inhibits the growth and sporulation at 5 mg/ml concentrations, emerging as a probable CotH inhibitor. Further, the compound's toxicity was evaluated by adding it to the feed of C.elegans, and the finding suggests that the bacoside is reasonably safe at the studied concentration. The findings project bacoside A as a potential anti-mucorale lead compound that can be further validated with preclinical and clinical studies.

Rhizopus oryzae is one of the major causative agents of mucormycosis. The disease has a poor prognosis with a high mortality rate, and resistance towards current antifungal drugs poses additional concern. The disease treatment is complicated with antifungals; therefore, surgical approach is preferred in many cases. A comprehensive understanding of the pathogenicity-associated virulence factors of R. oryzae is essential to develop new antifungals against this fungus. Virulence factors in R. oryzae include cell wall proteins, spore germination proteins and enzymes that evade host immunity. The spore coat protein (CotH3) and high-affinity iron permease (FTR1) have been identified as promising therapeutic targets in R. oryzae. In-silico screening is a preferred approach to identify hit molecules for further in-vitro studies. In the present study, twelve bioactive molecules were docked within the active site of CotH3 and FTR1. Further, molecular dynamics simulation analysis of best-docked protein-ligand structures revealed the dynamics information of their stability in the biological system. Eugenol and isoeugenol exhibited significant binding scores with both the protein targets of R. oryzae and followed the Lipinski rule of drug-likeness. To corroborate the in-silico results, in-vitro studies were conducted using bioactive compounds eugenol, isoeugenol, and myristicin against R. oryzae isolated from the soil sample. Eugenol, isoeugenol exhibited antifungal activity at 156 µg/mL whereas myristicin at 312 µg/mL. Hence, the study suggested that eugenol and isoeugenol could be explored further as potential antifungal molecules against R. oryzae.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and despite its clinical significance, there is an absence of established genome manipulation techniques to conduct molecular pathogenesis studies. In this study, we generated a spontaneous uracil auxotrophic strain and developed a genetic transformation procedure to analyze molecular mechanisms conferring antifungal drug resistance. With this new model, phenotypic analyses of gene deletion mutants were conducted to define Erg3 and Erg6a as key biosynthetic enzymes in the M. circinelloides ergosterol pathway. Erg3 is a C-5 sterol desaturase involved in growth, sporulation, virulence, and azole susceptibility. In other fungal pathogens, erg3 mutations confer azole resistance because Erg3 catalyzes the production of a toxic diol upon azole exposure. Surprisingly, M. circinelloides produces only trace amounts of this toxic diol and yet, it is still susceptible to posaconazole and isavuconazole due to alterations in membrane sterol composition. These alterations are severely aggravated by erg3Δ mutations, resulting in ergosterol depletion and, consequently, hypersusceptibility to azoles. We also identified Erg6a as the main C-24 sterol methyltransferase, whose activity may be partially rescued by the paralogs Erg6b and Erg6c. Loss of Erg6a function diverts ergosterol synthesis to the production of cholesta-type sterols, resulting in resistance to amphotericin B. Our findings suggest that mutations or epimutations causing loss of Erg6 function may arise during human infections, resulting in antifungal drug resistance to first-line treatments against mucormycosis.

The Mucor species complex comprises a variety of opportunistic pathogens known to cause mucormycosis, a potentially lethal fungal infection with limited therapeutic options. The only effective first-line treatments against mucormycosis consist of liposomal formulations of amphotericin B and the triazoles posaconazole and isavuconazole, all of which target components within the ergosterol biosynthetic pathway. This study uncovered M. circinelloides Erg3 and Erg6a as key enzymes to produce ergosterol, a vital constituent of fungal membranes. Absence of any of those enzymes leads to decreased ergosterol and consequently, resistance to ergosterol-binding polyenes such as amphotericin B. Particularly, losing Erg6a function poses a higher threat as the ergosterol pathway is channeled into alternative sterols similar to cholesterol, which maintain membrane permeability. As a result, erg6a mutants survive within the host and disseminate the infection, indicating that Erg6a deficiency may arise during human infections and confer resistance to the most effective treatment against mucormycoses.