Search

Mucormycosis is an opportunistic fungal infection with a high mortality rate. Though typically associated with diabetes and other conditions that affect innate immune function, infections can also be precipitated by conditions such as trauma and burns. Burn patients are particularly susceptible to fungal infections due to the immune dysfunction that often accompany their wounds. Indeed case series have described mucormycosis to occur in patients with burn injuries, however the factors contributing to mortality have not been well described. Thus, the purpose of our review was to identify factors contributing to morbidity and mortality in burn patients with Mucormycosis.A systematic review of the literature of mucormycosis infection in burn injury patients was performed on Pubmed and Google Scholar using the keywords: Mucor, Mucorales, Mucormycosis, Mucormycotina, Zygomycosis and burn or thermal injury. Clinical trials, observational studies, case reports, and case reviews were included if they provided information regarding mortality in adult and pediatric burn patients diagnosed with mucormycosis, review articles, non-English articles, and articles without patient information were excluded. No time limit was placed on our review. Individual patient data was stratified based on mortality. Statistical analysis was performed to investigate the relationship between patient risk factors and mortality, and the Oxford Level of Evidence was used to evaluate study quality.46 articles were included in our final review, encompassing 114 patients. On average, survivors had a total body surface area (TBSA)% of 46 (SD 19.8) while non-survivors had a TBSA of 65% (SD 16.4), and this difference was significant (p .001). Patients with disseminated mucormycosis experienced an 80% mortality rate compared to 36% mortality rate in patients with localized disease (p .001). We found no statistically significant difference in mean age (p .05), diabetes (p .05), mean delay in diagnosis (p .05), time to antifungal therapy (p .05), or type of therapy used (p .05) between survivors and non-survivors. Our review was limited by the lack of prospective, controlled trials; thus, our review primarily consists of case reports.Disseminated infections and higher TBSA both increased the risk of mortality in burn patients with mucormycosis, while diabetes did not increase mortality risk. The severity of the initial injury and infection locations must be taken into consideration to inform patient prognosis.

Mucormycosis is a life-threatening, invasive fungal disease that mostly affects immunocompromised hosts. In this study, we aimed to assess the clinical presentations and outcomes of patients with mucormycosis in a tertiary care hospital in the western region of Saudi Arabia.A retrospective chart review of patients diagnosed with mucormycosis was conducted from January 2009 to December 2019 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. We aimed to assess and analyze the characteristics of patients with mucormycosis, their clinical presentations, and treatment outcomes.Fifteen cases were identified as proven or probable mucormycosis according to the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Most cases (n = 11, 73.3 %) were categorized as proven, whereas four cases (26.7 %) were categorized as probable. The median patient age was 29.5 years (range, 6-79 years). The most common underlying etiology was hematological malignancies (7 cases), followed by diabetes mellitus (5 cases), and trauma from a motor vehicle accident (4 cases). Cutaneous mucormycosis was the predominant presentation, as noted in seven cases (46.6 %), followed by rhino-orbito-cerebral mucormycosis in four cases (26.7 %), and pulmonary mucormycosis in two cases (13.3 %). Rhizopus (six cases) and Mucor (four cases) were the two main fungal isolates. Eight patients were treated with amphotericin B lipid complex (53.3 %) alone, and three patients were treated with a combination of amphotericin B lipid complex and posaconazole. Overall, 11 (73.3 %) patients died, two of whom died before a confirmed diagnosis.The mortality among patients with mucormycosis was high. Relatively better survival was observed among cutaneous cases. A combination of new diagnostic technologies, optimized use of available antifungal options, development of new antifungal agents, and consistent implementation of public health policies may help reduce mortality rates from mucormycosis in Saudi Arabia.

Background Osteomyelitis of the jawbone is mostly secondary to radiation exposure or bone remodelling drugs, with the mandible being commonly involved. Maxillary osteomyelitis risk is low owing to its high vascularity. This study was undertaken to evaluate risk factors, presentation, management and outcomes of maxillary osteomyelitis caused due to reasons other than irradiation and bone remodelling drugs. Methods Patient records diagnosed with maxillary osteomyelitis were evaluated for demographic details, risk factors, clinical presentation, radiological features, treatment performed and outcomes. Results In 38 patients with non-irradiated and non-drug–induced osteomyelitis, 13 involved the maxilla, seven were localized to the posterior maxilla and 10 showed paranasal sinus involvement. Dissemination to the cavernous sinus and cerebral spread was seen in one. Clinical findings included oroantral communication, pain and draining sinus. Imaging showed diffuse bone destruction areas with or without evidence of bony sequestrum. The most common systemic risk factor was diabetes mellitus. Maxillary osteomyelitis was associated with tooth extraction in eight cases. Surgical management included debridement, sequestrectomy, functional endoscopic sinus surgery, maxillectomy and reconstruction of soft tissue defect with local and regional flaps. Complete recovery was seen in 11 patients. Mortality was seen in two patients with mucormycosis having disseminated infection. Conclusion Compared with previous literature, a relatively higher ratio of maxillary involvement was reported. Diabetes mellitus was the most common risk factor, followed by osteopetrosis and tooth extraction. Osteomyelitis secondary to mucormycosis in immunocompetent patients was relatively localized and gave favourable response to management compared with patients with diabetes mellitus.

This clinical report presents the rehabilitation of extensive hard and soft tissue defects caused by rhino-orbital-cerebral mucormycosis as a result of untreated diabetes mellitus. The patient underwent subtotal maxillectomy and was rehabilitated with an implant-supported maxillofacial prosthesis with zygomatic and pterygoid implants by following an immediate loading protocol.

Mucormycosis infection of the maxillofacial region and brain has been associated with coronavirus disease 2019 (COVID-19) infection. Mucormycosis was relatively a rare infection before COVID-19, and imaging findings are not very well described.A retrospective imaging study of 101 patients diagnosed with COVID-19-associated mucormycosis by histopathology and/or culture was performed. All patients underwent computed tomography and/or magnetic resonance imaging based on the clinical condition of the patient and on consensus decision by the team of treating physicians. A simple 3-stage classification system based on imaging findings was adopted.One hundred one cases were included in the final analysis (mean age = 55.1 years; male/female ratio = 67:34). The affected patients had diabetes in 94% of the instances (n = 95), 80.1% (n = 81) received steroids), whereas 59.4% (n = 60) patients received supplemental oxygen. The majority underwent surgical intervention, whereas in 6 cases, patients were treated with antibiotic regimens. Sixty subjects improved following therapy, whereas 18 eventually succumbed to the illness. We noted a significant positive correlation between the imaging stage and outcomes. No association was seen between other clinical parameters and final clinical outcomes. Salient imaging findings include lack of normal sinonasal mucosal enhancement, perisinus inflammation, ischemic optic neuropathy, perineural spread, pachymeningeal enhancement, and presence of strokes.We describe the imaging findings in the largest cohort of patients with rhino-orbito-cerebral mucormycosis in the context of the current COVID-19 pandemic. A simplified staging system described here is helpful for standardized reporting and carries prognostic information.

Introduction Rhinocerebral mucormycosis is extremely fatal, with mortality rates ranging from 85-93% despite the best treatment in immunocompromised patients. We emphasize the importance of early diagnosis, repeated debridement, and aggressive antifungal treatment to reduce mortality. Case summary We report six cases (five male and one female), with a mean age of 51 years who were diagnosed to have mucormycosis from 2017 to 2019. All patients were diabetic. Intracranial involvement and orbital involvement were found in four cases. Facial nerve palsy was seen in two cases, one without any apparent otological involvement. Aggressive serial debridement and amphotericin B was started. Posaconazole was added subsequently to the treatment in two cases. One patient succumbed to the disease five months after discharge. The other five patients are on regular follow-up for a mean duration of 14 months at the end of which two had residual disease which was under control. Discussion Repeated surgical debridement with an early aggressive and combination antifungal therapy can result in good outcomes even in advanced mucormycosis. Concurrent management of the underlying pathology, monitoring of liver and kidney functions, and therapeutic drug monitoring are useful to ensure smooth and effective treatment.

Introduction India reported a severe public health challenge not only due to the COVID-19 outbreak but also the increasing number of associated mucormycosis cases since 2021.This study aimed at developing artificial intelligence based models to predict the risk of mucormycosis among the patients at the time of discharge from hospital. Methods The dataset included of 1229 COVID-19 positive patients, and additional 214 inpatients, COVID-19 positive as well as infected with mucormycosis. We used logistic regression, decision tree and random forest and the extreme gradient boosting algorithm. All our models were evaluated with 5-fold validation to derive a reliable estimate of the model error. Results The logistic regression, XGBoost and random forest performed equally well with AUROC 95.0, 94.0, and 94.0 respectively. The best accuracy and precision (PPV) were 0.91 ± 0.026 and 0.67 ± 0.0526, respectively achieved by XGBoost, followed by logistic regression. This study also determined top five variables namely obesity, anosmia, de novo diabetes, myalgia, and nasal discharge, which showed positive impact towards the risk of mucormycosis. Conclusion The developed model has the potential to predict the patients at high risk and thus, consequently initiating preventive care or aiding in early detection of mucormycosis infection. Thus, this study, holds potential for early treatment and better management of patients suffering from COVID-19 associated mucormycosis.

Disseminated Rhizomucor pusillus infection is a very rare but fatal complication in immunocompromised patients, because of aggressive clinical process with delayed diagnosis by routine laboratory tests. Recently, cell-free DNA next-generation sequencing (cfDNA NGS) has been used for the timely detection of infectious pathogens including mucormycosis. Herein, we described an 18-year-old male with Philadelphia-like acute lymphoblastic leukemia who received a timely diagnosis of R. pusillus infection by cell-free DNA next-generation sequencing, and confirmed by silver staining and qPCR on biopsy tissue. To the best of our knowledge, this was the first case of disseminated R. pusillus infection detected by cfDNA NGS and confirmed by histology in an adult leukemia patient. In addition, this case was supposed to be the most extensive R. pusillus infection diagnosed, involving the lung, skin, liver, kidney, spleen and brain, and the only one case who survived the infection had a favorable outcome through treatment with liposome amphotericin B sequential posaconazole. This case suggested that cfDNA NGS could be used to successfully detect rare pathogen infections, and this was especially important for R. pusillus because timely diagnosis and effective treatment could improve the prognosis of this kind of patient.

Summary Purpose To evaluate our patients with rhino-orbito-cerebral mucormycosis according to a new scoring system and to compare those who underwent orbital exenteration persuant to a new threshhold. Methods Mucormycosis is a fungal disease that can be of acute onset, aggressive, and angioinvasive. Aggressive surgical debridement, long-term systemic antifungal therapy, and treatment of underlying predisposing factors are essential to the treatment. However, orbital exenteration is a very difficult decision to make, particularly in patients with orbital involvement, because there is little information in the literature, resulting in limited support for making this aggressive surgical decision. In this study, our 43 cases of mucormycosis were evaluated in terms of orbital exenteration using a scoring system (including clinical signs and symptoms, ophthalmoscopic findings, and radiologic results) developed by Shah et al., which establishes indications for orbital exenteration in mucormycosis. Results According to our study, if the threshold score for exenteration is 19.0, the sensitivity was 100% and specificity was 97%, providing better results than the 23.0 threshold score determined by the reference study for exenteration. When these two score thresholds were compared, there was a statistically significant difference. Conclusion We believe that this scoring system may be beneficial to use for orbital exenteration in patients with mucormycosis. Prospective studies in large case series are required to determine the most appropriate threshold score.

Background Diabetic ketoacidosis (DKA) has increased in prevalence in the emergency department (ED) in recent years. The complications of DKA are life threatening and necessitate rapid identification and management. Pediatric complications include cerebral edema, venous thrombosis, acute kidney injury, and severe infections including necrotizing fasciitis and mucormycosis. Rhinocerebral mucormycosis carries a high mortality rate and requires early treatment with antifungals and surgical debridement. Case Report A 16-year-old boy with no significant past medical history presented to the ED with new-onset DKA complicated by hypothermia, hyperosmolar hyperglycemic state, cerebral edema, and multifactorial shock. During a complicated pediatric intensive care unit admission, he was found to have fatal invasive rhinocerebral mucormycosis, causing internal carotid artery occlusion with evidence of both direct and hematogenous spread into his brain. Why Should an Emergency Physician Be Aware of This? Early identification of shock and appropriate management with intravenous fluids, vasopressors, and reversal of the underlying process is key in hypotensive children. In pediatric DKA, the emergency physician must consider cerebral edema, appropriate fluid resuscitation, and identify the likely precipitants leading to the onset of DKA. Thorough workup for potential precipitants should be initiated in the ED, searching for etiologies including infection, intoxication, insulin deficiency, inflammation, and ischemia. We must remember that pediatric patients, especially those with new DKA, are susceptible to life-threatening infection, including mucormycosis. Mucormycosis is a rare diagnosis, and management includes antifungal therapies and involvement of otorhinolaryngology.

Introduction Mucormycosis with oral involvement (OIM) is a rare opportunistic and lethal mycosis, which has increased in the last decade and is generally associated with uncontrolled diabetes and neutropenia. Methods A retrospective study of cases with OIM was carried out in a tertiary-care center. Mycological and histological examinations were performed, and the isolated organisms were identified by morphology and molecular biology. Results Fifty-five OIM patients were included, with a median age of 38 years (61.8% males). The most frequent associated disease was type-2 diabetes mellitus (61%), followed by neutropenia due to acute lymphocytic leukemia (27%). The main presentation was palatal and mandibular ulcers (92.7%) and, to a lesser extent, gingival and lingual necrosis. The diagnosis was established by mycological and histopathological studies. The most frequent fungi isolated was Rhizopus arrhizus (67.2%). Conclusion OIM is a rapidly progressing disease, therefore, an early diagnosis and the proper control of predisposing factors is necessary, and consequently, contributing to improve the outcome of mucormycosis.

Invasive pulmonary mucormycosis is a potentially fatal infection that can occur in immunosuppressed patients such as those who have undergone orthotopic heart transplant (OHT). High-dose intravenous antifungal agents, including amphotericin B, are generally accepted as the first-line medical treatment, with prompt surgical resection of lesions if feasible. The body of evidence guiding treatment decisions, however, is sparse, particularly regarding adjustment of immunosuppression during acute infection and long-term recovery. We present 2 cases of patients with pulmonary mucormycosis occurring within the first 6 months after OHT, both of whom successfully recovered after appropriate medical and surgical treatment, and we highlight differences in immunosuppression management strategies for this life-threatening condition.

Most fungal infections are common in humans. Pathogenic fungi are opportunistic but can cause fungal infection disease in patients with immunocompromised conditions, such as malignancy, chemotherapy, transplantation, acquired immunodeficiency syndrome, and usage of immunosuppressant drugs. Most invasive infections are caused by Aspergillus species, mucormycetes, Cryptococcus species, and Candida species. This article focuses on environmental fungi such as Aspergillus species and mucormycetes because the mode of transmission is different. The purpose of this article is to discuss invasive fungal infections (IFIs) caused by environmental fungi and to educate critical care nurses about infection control and risk mitigation to prevent IFIs.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during the infection and after the virus clears out. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed only on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia under the care of ENT, Ophthalmology, Neurosurgery and Neurology. She is currently on anti-fungal treatment as advised by infectious disease department.

As the battle against the deadly Covid-19 pandemic is still continuing worldwide, several complications are being reported in patients who have recovered post-covid. One such lethal complication being reported in patients in India in recent times, who have tested positive for Covid-19 and are gradually recovering, is a fungal disease called Mucormycosis or the black fungus. With several hundreds of cases being reported all over the country, it has triggered an additional wave of panic among the general public. Post-Covid-19 patients who are more vulnerable to Mucormycosis are those with a history of poorly controlled diabetes mellitus and also those who are immuno-compromised and have been treated with steroids and other drugs for Covid-19. The aim of this short review is to briefly cover the epidemiology of mucormycosis, its possible pathophysiology in Post Covid scenario, the clinical presentation and its diagnosis and management.

This review aimed to study molecular mechanisms for high incidence of life-threatening mucormycosis infection in COVID19 cases during second wave of SARS CoV2 pandemic in India. Hyperglycaemia, impaired immunity, acidosis, raised ferritin, glucocorticoid therapy, and COVID19 specific other factors have been implicated in pathogenesis of COVID19 associated mucormycosis (CAMM). Endoplasmic reticulum chaperone 'Glucose Related Protein 78' (GRP78), also involved in SARS CoV2 entry, is the host receptor for invasion by Mucorales. GRP78 is over-expressed by SARS CoV2, hyperglycaemia and ferritin. Delta variant of SARS CoV2 and indiscriminate use of steroids were distinguishing features of second wave and appear to upregulate GRP78 through intricate interplay between internal and external milieu. Common invasive fungal infections like candidiasis and aspergillosis, not utilizing GRP78 as receptor, were inconspicuous. Further molecular research to unravel mechanisms involved in the pathogenesis of CAMM shall effectively complement existing strategies for its prevention and treatment.

Even before the onslaught of COVID-19 pandemic could settle, the unprecedented rise in cases with COVID-19 associated mucormycosis pushed the medical health to the fringe. Hyperglycaemia and corticosteroids appear to be the most consistent associations leading to the commonest manifestation of mucormycosis, Rhino-Orbito-Cerebral Mucormycosis. To address challenges right from categorisation and staging of the disease to the management of relentless progression, a multi-disciplinary expert committee was formed to handle the task in an evidence-based format to enforce best practices. The report of the committee on one hand attempts to succinctly present the currently available evidence while at the other also attempts to bridge the evidence-deficient gaps with the specialty-specific virtuosity of experts.

We describe two fatal cases of COVID-19 in which Rhizopus microsporus and Lichtheimia corymbifera were cultured from endotracheal aspirate samples. Both patients had no underlying comorbidities other than obesity. Despite antifungal therapy, both cases developed septic shock and progressive refractory hypoxemia without evidence of other underlying infections. It is unclear whether isolation of these fungal organisms represents invasive disease or corresponds to an epiphenomenon of critical illness. Yet, patients suffering from COVID-19 may be at risk of superinfection from a broader range of fungal organisms than previously thought.

To obtain a national overview of the epidemiology and management of invasive fungal infections (IFIs) in France for severely immunocompromised children who were treated for acute leukemia or had undergone allogeneic hematopoietic stem cell transplantation (a-HSCT).We performed a national multicenter retrospective study to collect epidemiologic data for proven and probable IFIs in children with acute leukemia under first- line or relapse treatment or who had undergone a-HSCT. We also conducted a prospective practice survey to provide a national overview of IFI management in pediatric hematology units.From January 2014 to December 2017, 144 cases of IFI were diagnosed (5.3%) in 2721 patients, including 61 cases of candidiasis, 60 cases of aspergillosis, and 23 cases of infection with "emergent" fungi, including 10 cases of mucormycosis and 6 cases of fusariosis. The IFI rate was higher in patients with acute myelogenous leukemia (12.9%) (OR, 3.24; 95% CI, 2.15-4.81; P.0001) compared with the rest of the cohort. Patients undergoing a-HSCT had an IFI rate of only 4.3%. In these patients, the use of primary antifungal prophylaxis (principally fluconazole) was associated with a lower IFI rate (OR, 0.28; 95% CI, 0.14-0.60; P = 4.90 ×10The emerging fungi and new antifungal resistance profiles uncovered in this study should be considered in IFI management in immunocompromised children.

Mucormycosis is a deadly infection which is caused by fungi of the order Mucorales including species belonging to the genus Rhizopus, Mucor, Mycocladus, Rhizomucor, Cunninghamella, and Apophysomyces. Despite antifungal therapy and surgical procedures, the mortality rate of this disease is about 90-100% which is exceptionally high. The hypersensitivity of patients with raised available serum iron indicates that the Mucorales are able to use host iron as a critical factor of virulence. This is because iron happens to be a crucial element playing its role in the growth of cells and development. In this review, we have described Lactoferrin (Lf) as a potential iron-chelator. Lf is a naturally occurring glycoprotein which is expressed in most of the biological fluids. Moreover, Lf possesses exclusive anti-inflammatory effects along with several anti-fungal effects that could prove to be helpful to the pathological physiology of inexorable mucormycosis cases. This literature summarises the biological insights into the Lf being considered as a potential fungistatic agent and an immune regulator. The review also proposes that unique potential of Lf as an iron-chelator can be exploited as the adjunct treatment for mucormycosis infection.

Graphical abstract, Background The incidence of devastating opportunistic coinfections in patients with COVID-19 infection, their imaging features and their morbidity and mortality consequences need to be unraveled. Methods This is a case series presenting the radiologic features and clinical presentation of acute invasive fungal rhino-orbital-cerebral sinusitis (AIFS) in eight hospitalized patients with confirmed COVID-19 infection. Results Our patient cohort presented with symptoms of the invasive fungal disease within 12–35 days from their initial presentation with COVID-19 infection. The cross-sectional imaging features of AIFS associated with COVID-19 infection do not differ from those reported in the literature for AIFS associated with other risk factors, yet our patients had features of aggressive late-stage forms with high morbidity and mortality rate. Conclusion AIFS is a possible encounter in patients with COVID-19 patients and radiologists should be familiar with its imaging features.

Case Presentation A 66-year-old woman with a history of diabetes presented with an intermittent low-grade fever, cough, shortness of breath, and decreased activity tolerance over a 3-month period. She is a farmer, and denied a history of chronic pulmonary disease. Her only medical history was type 2 diabetes managed without medication. She denied smoking or tobacco use. She did not report any recent travel and denied having birds at home. Imaging at a local hospital showed left lower lobe atelectasis with a small pleural effusion. An infection with mucormycosis was diagnosed through transbronchial biopsy. The patient was given nebulized amphotericin B along with concurrent IV liposomal amphotericin B for a total of 15 days. She experienced no significant improvement in symptoms during therapy and, in fact, developed worsening, progressive dyspnea.

Purpose Mucormycosis is an uncommon aggressive, opportunistic infection that can produce widespread orofacial tissue necrosis. This primarily affects immunocompromised individuals. It is the deadliest and most rapidly progressing type of human-affecting fungal infection. The aim of the study is to investigate the diagnostic criteria and treatment approach in 10 cases of mucormycosis in the author's institute from 2008 to 2019. Moreover, a review of the English literature presents all cases of mucormycosis after tooth extraction. Materials and Methods Ten patients at our institute have been treated. They were evaluated and discussed as per their diagnostic criteria, surgical treatment, and mortality rates. Results All 10 immunocompromised patients had a primary hematologic malignancy. The criteria for a positive diagnosis were clinical symptoms and a biopsy for microbiological culture and histologic analysis. Each patient was subjected to vigorous surgical resection and underwent antifungal treatment. Seven patients died because of their main disease. Owing to the unregulated spread of mucormycosis, 2 patients died. Four cases were diagnosed after maxillary tooth extraction. Conclusions The most important factor for patient survival tends to be the management of the underlying disease with early detection and active surgical and antifungal action. Four of 10 cases diagnosed with mucormycosis appeared after tooth extraction, a relatively high number compared with the literature. Therefore, it is the dental profession's obligation to be familiar with the possibility of the potentially severe and possibly fatal complication.

Coronavirus disease 2019 (COVID-19), may present with a myriad of clinical manifestations and complications. Patients with COVID-19 are at increased risk of pulmonary thromboembolism, acute cardiac injury, arrhythmias, acute stroke, and secondary infections. Mucormycosis is a catastrophic fungal infection characterized by vascular invasion, thrombosis, and necrosis of tissues. We report five cases of COVID-19 infection, who developed rhino-orbital mucormycosis, during the course of treatment. Early recognition of this life-threatening infection is the key to allow for optimal treatment and improved outcomes.

This is the first published case report of a child with acute lymphatic leukemia developing a fatal mucormycosis during blinatumomab treatment. The patient showed multiple, systemic thromboembolic lesions with ischemia, bleeding and infarction in almost all organs. The child succumbed to increased brain pressure resulting in cerebral herniation. This case particularly illustrates the fulminant progression and huge challenges of diagnosing and treating mucormycosis in children with hemato-oncological diseases during treatment with targeted therapeutic antibodies (blinatumomab).

A 61-year old lady with poorly-controlled type 2 diabetes mellitus was diagnosed with rhino-orbital-cerebral mucormycosis following presentation with sinusitis, ophthalmoplegia, proptosis and facial numbness. She was treated successfully with aggressive surgical intervention including orbital exenteration, accompanied by anti-fungal therapy with liposomal amphotericin B and posaconazole, followed by isavuconazole as salvage therapy. We discuss the challenges around optimising antifungal therapy of this lethal infection in the context of hepatic and renal toxicity.

Case Presentation A 47-year-old man with poorly controlled diabetes mellitus (glycosylated hemoglobin 12%) presented to the ED with a 1-week history of fevers, productive cough, and dyspnea. The patient was febrile and hypoxemic on presentation; laboratory testing was remarkable for hyperglycemia and ketoacidosis. The initial chest CT scan showed right lower lobe consolidation and ground-glass opacities ( Fig 1 A). He was admitted to the ICU and administered IV antibiotics (cefepime and vancomycin) for the treatment of community-acquired bacterial pneumonia.

Infections caused by mucorales, with an increasing incidence after candidiasis and aspergillosis, are characterized by the fast angioinvasion of blood vessels and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous, digestive or disseminated infections, and their spread is favored by certain underlying diseases (diabetes, kidney failure) and risk factors (neutropenia, immunosuppression, iron overload). These infections have a high mortality rate, over 40% in many series, and the key to their cure depends on both an early diagnosis and an antifungal treatment, associated in most cases with extensive surgical debridement and other adjunctive therapies. Currently, there are international guidelines, not only local ones, for the management of mucormycosis, in which it is considered by consensus and with a strong recommendation that first-line treatment with high-dose liposomal amphotericin B is the best choice. The combined antifungal treatment of polyene agents with triazoles or candins remains in open debate.

Objectives Pulmonary mucormycosis (PM) is increasingly being reported in immunocompromised patients and has a high mortality. Our aim was to assess the mortality of PM and its trend over time. We also evaluated the role of combined medical–surgical therapy in PM. Methods We performed a systematic review of Pubmed, Embase, and Cochrane central databases. Studies were eligible if they described at least five confirmed cases of PM and reported mortality. We also assessed the effect of combined medical–surgical therapy versus medical treatment alone on PM mortality. We used a random-effects model to estimate the pooled mortality of PM and compared it across three time periods. The factors influencing mortality were assessed using meta-regression. We evaluated the risk difference (RD) of death in the following: subjects undergoing combined medical–surgical therapy versus medical therapy alone, subjects with isolated PM versus disseminated disease, and PM in diabetes mellitus (DM) versus non-DM as a risk factor. Results We included 79 studies (1544 subjects). The pooled mortality of PM was 57.1% (95% confidence interval [CI] 51.7–62.6%). Mortality improved significantly over time (72.1% versus 58.3% versus 49.8% for studies before 2000, 2000–2009, and 2010–2020, respectively, p 0.00001). This improved survival was confirmed in meta-regression after adjusting for the study design, the country's income level, and the sample size. Combined medical–surgical therapy was associated with a significantly lower RD (95%CI) of death: –0.32 (–0.49 to –0.16). The disseminated disease had a higher risk of death than isolated PM, but DM was not associated with a higher risk of death than other risk factors. Conclusions While PM is still associated with high mortality, we noted improved survival over time. Combined medical–surgical therapy improved survival compared to medical treatment alone.

Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.

Background Many studies have shown that invasive pulmonary aspergillosis, cryptococcosis, and mucormycosis can mimic radiographic and clinical features of primary lung cancer. However, more research surveying the incidence and outcomes of these fungal infections among patients with a history of lung cancer is needed. The aim of this study was to describe the occurrence and clinical outcomes of opportunistic invasive fungal infections that can mimic tumors in non–small-cell lung cancer patients. Patients and Methods Patients seen at Stanford University Medical Center from January 1, 2007, to May 1, 2020, with pulmonary aspergillosis, cryptococcosis, or mucormycosis after non–small-cell lung cancer (NSCLC) diagnosis were reviewed. The European Organization for Research and Treatment of Cancer National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to classify patients with evidence of proven or probable invasive fungal infection within our cohort. Results A total of 12 patients with proven or probable invasive mold infection (including 8 cases of aspergillosis) and 1 patient with proven cryptococcosis were identified, without any cases of mucormycosis. Of this cohort, 6 patients (46%) showed radiographic findings that were found to be most consistent with lung cancer by radiologists. Eight cases (62%) were suspected of cancer recurrence or progression by the treatment team on the basis of additional considerations of medical history and clinical symptoms. Most patients had active NSCLC or had a history of recurrence without active NSCLC at the time of fungal discovery (11 patients; 85%). Most patients died without full recovery (7 patients; 54%). Conclusions Invasive pulmonary aspergillosis and cryptococcosis can often be mistaken as cancer recurrence or progression in patients with a history of NSCLC because of mimicking radiographic and clinical characteristics.

Case Presentation A 51-year-old woman with a medical history of poorly controlled type 1 diabetes mellitus, hyperthyroidism, and tobacco abuse was admitted to the hospital with persistent nausea, vomiting, abdominal discomfort, dry cough, rhinorrhea, and sore throat. She denied fevers, chills, rigors, shortness of breath, hemoptysis, nasal congestion, postnasal drip, and facial pain. She denied any sick contacts, and there was no recent travel outside of Chicago.

The second wave of COVID-19 due to Delta (B.1.617.2) variant led to the rapid rise of total coronavirus and COVID-associated mucormycosis cases reported from India. Hence, the current perspective explores the possible causes of rapid upsurge in COVID-associated mucormycosis cases, which was accounted for over 70% of global cases. The five most probable factors associated with the increase of mucormycosis in COVID-19 patients include diabetes mellitus, steroids overdose, high iron levels, immuno-suppression, combined with other possible factors such as unhygienic conditions, prolonged hospitalization, use of ventilators and leaky humidifiers in oxygen cylinders, creates an ideal environment for contracting mucormycosis. However, these cases could be brought down by disseminating simple preventive measures and creating awareness among the medical society and general public on this rare and deadly contagion of COVID-associated mucormycosis. The identification of the early symptoms will help to restrict the spread of lethal fungal diseases. Further, a collaborative team of surgeons, ophthalmologists, physicians, otolaryngologists specialists would be required in the hospital wards to proceed with quick surgeries on severely impacted patients., Graphical Abstract Image, graphical abstract

Summary: Background: Severe COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19. Methods: In this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients. Findings: The median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of active viral replication outside the respiratory tract in three of five patients. Interpretation: Our series supports clinical data showing that the four dominant interrelated pathological processes in severe COVID-19 are diffuse alveolar damage, thrombosis, haemophagocytosis, and immune cell depletion. Additionally, we report here several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation, which require additional investigation to understand their role in COVID-19. Funding: Imperial Biomedical Research Centre, Wellcome Trust, Biotechnology and Biological Sciences Research Council.

Background An outbreak of post-kidney transplant cutaneous mucormycosis (PK-CM), a severe and even fatal complication in immunocompromised patients, occurred in our institution. The objective of this study was to compare the usual fixation of sterile wound dressings with non-sterile elastic bandages and fixation with sterile bandages processed at our centralized sterile services department with regard to PK-CM prevention. Methods We conducted a before-and-after trial in a private tertiary care hospital. The pre-intervention cohort (n = 16) included all patients who had undergone kidney transplant (KT) during the outbreak (June 2010-April 2011), and the post-intervention cohort (n = 49) included all patients who had undergone KT between May 2011 and October 2013. From May 2011, only bandages sterilized by the centralized sterile services department were used to fix wound dressings of KT patients. Results Differences in age (50.2 years vs 51.3 years), sex (43.8% male vs 59.2% female), weight (63.3 kg vs 69.7 kg), hemodialysis vintage (55.6 months vs 47.8 months), and other risk factors were not observed between the pre- and post-intervention cohorts, respectively. PK-CM incidence dropped from 25% in the pre-intervention cohort (4/16) to 0% in the post-intervention cohort (0/49). Relative risk was 0 (P = .003). Conclusions With regard to KT patients and sterile wound dressing fixation with non-sterile bandages versus the use of autoclaved bandages, fixation with autoclaved bandages proved to be effective for cutaneous mucormycosis outbreak control and prevention in our institution.

Mucormycosis isolated to the mandible is a rare presentation occurring generally after dental procedures. The case we report presented with discharging sinuses over facial region with radiological appearance of isolated osteomyelitis of the mandible. The patient used to apply an addictive dental powder over his teeth leading to caries. Following this, he pulled out all his teeth, which probably led to his condition. Invasive sampling revealed mucormycosis. An extensive search for an underlying immunodeficiency revealed that the patient had chronic granulomatous disease (CGD). Despite a prolonged course of L-Amphotericin B, the patient continued to have intermittent pus discharge and surgical debridement and curettage was eventually required. The patient had a chronic course with minimal soft tissue involvement which initially did not raise the suspicion of mucormycosis. The main learning point is that an unusual invasive fungal infection in an otherwise healthy host can be the first symptom of an underlying primary immunodeficiency, like CGD. Invasive fungal infections in patients with CGD often have an indolent course., Highlights • Mucormycosis isolated to the mandible is a rare presentation, occurring generally after dental procedures. • Self-extraction of teeth as in our patient can result in isolated mucormycosis of the mandible. • Isolated mucormycosis of the mandible can be a presenting symptom of chronic granulomatous disease. • Combination of medical and surgical treatment is usually needed in mandibular mucormycosis.

Purpose Pulmonary mucormycosis is a highly lethal invasive fungal infection usually found in immunocompromised patients. We report herein the case of an adult woman who developed pulmonary mucormycosis with possible systemic dissemination after recovering from acute liver failure secondary to acetaminophen overdose. Results Our case developed an invasive pulmonary mucormycosis with probable systemic dissemination. She did not suffer from any immunocompromising disease other than severe acute liver failure. She did not survive the disease, although she received appropriate antifungal treatment. We also performed a systematic review of the literature on pulmonary mucormycosis, with or without dissemination, in immunocompetent patients. We found 16 cases of pulmonary or disseminated mucormycosis in immunocompetent patients. Fifty-seven percent of them died and none occurred after an acute liver failure episode. Conclusion This case report is the first one to present an invasive pulmonary mucormycosis infection after acute liver failure in an adult patient. The clinical course of this disease is highly lethal, even in immunocompetent adults.

Mucormycosis is a life-threatening fungal infection, particularly in immunocompromised patients. Mucormycosis has been reported to show resistance to available antifungal drugs and was recently found in COVID-19 as a co-morbidity that demands new classes of drugs. In an attempt to find novel inhibitors against the high-affinity iron permease (FTR1), a novel target having fundamental importance on the pathogenesis of mucormycosis, 11,000 natural compounds were investigated in this study. Virtual screening and molecular docking identified two potent natural compounds [6',7,7,10',10',13'-hexamethylspiro[1,8-dihydropyrano[2,3-g]indole-3,11'-3,13-diazatetracyclo[5.5.2.01,9.03,7]tetradecane]-2,9,14'-trione and 5,7-dihydroxy-3-(2,2,8,8-tetramethylpyrano[2,3-f]chromen-6-yl)chromen-4-one] that effectively bind to the active cavity of FTR1 with a binding affinity of -9.9 kcal/mol. Multiple non-covalent interactions between the compounds and the active residues of this cavity were noticed, which is required for FTR1 inhibition. These compounds were found to have inhibitory nature and meet essential requirements to be drug-like compounds with a considerable absorption, distribution, metabolism, and excretion (ADME) profile with no toxicity probabilities. Molecular dynamics simulation confirms the structural compactness and less conformational variation of the drug-protein complexes maintaining structural stability and rigidity. MM-PBSA and post-simulation analysis predict binding stability of these compounds in the active cavity. This study hypothesizing that these compounds could be a potential inhibitor of FTR1 and will broaden the clinical prospects of mucormycosis.

The surge of COVID-19 associated Mucormycosis (CAM) in India during the second wave of COVID-19 led to lack of availability of amphotericin B(AmB). We retrospectively evaluated the outcome in 28 consecutive patients with CAM who received posaconazole (PCZ) or isavuconazole (ISVCZ) as sole or predominant therapy, based on factors like availability, affordability, site of infection or lack of treatment response. Therapeutic drug monitoring was used for PCZ in all casesfor ISVCZ in some cases. Higher trough levels were aimed to ensure therapeutic effect. Overall, 16 patients were cured, 5 patients improved, 6 patients died, of which 2 deaths were attributable to mucormycosis and 1 patient was lost to follow-up. The outcomes and survival were comparable to those reported in the literature. Although wider applicability of these results cannot be assumed, it leads to a speculation that treatment of mucormycosis with PCZ or ISVCZ, without AmB, is possible.

Objective Although invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. Methods We retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. Results We present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. Conclusion Our experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.

Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis.

Background Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases. Case Description We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature. Conclusions Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.

Mucormycosis is a fungal infection primarily afflicting immunocompromised or diabetic patients. Its presentation ranges from rhino-orbito-cerebral infections to disseminated mucormycosis with angioinvasion. We present a patient who developed a bowel obstruction one month after bone marrow transplant and was diagnosed with Rhizopus arrhizus diverticulitis despite antifungal therapy since transplantation. She underwent surgical removal with immediate fungal resurgence, declined further invasive intervention and was discharged on palliative isavuconazole. Seven months later she is alive with fungal containment. Keywords: Mucormycosis, Rhizopus arrhizus, Fungal diverticulitis, Salvage isavuconazole

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have.

Among 89 skulls from the Bijelo Brdo site in mainland Croatia dated between the 10th and 11th centuries, two show osteological features characteristic for lepromatous leprosy. Both skulls have female traits. An adult individual exhibits inflammatory changes on the palatine process, the alveolar process of the maxilla, the inferior nasal aperture, and on the anterior nasal spine. A younger individual, between 15 and 17 years at the time of death, exhibits less pronounced changes on the inferior nasal aperture, and the anterior nasal spine. Differential diagnosis excluded fungal infections (aspergillosis, mucormycosis), bacterial infections (actinomycosis, tuberculosis), and granulomatous disorders (sarcoidosis, and treponemal diseases). Molecular genetic analysis targeting the repetitive elements RLEP (37 copies/cell) and RepLep (15 copies/cell) of the M. leprae genome confirmed the presence of the disease in the adult individual. The possible geography of the spread of this infectious disease in Croatia is discussed.