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The Lancet. Infectious Diseases Dec 2019Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent... (Review)
Review
Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.
Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
Topics: Disease Management; Humans; Mucormycosis
PubMed: 31699664
DOI: 10.1016/S1473-3099(19)30312-3 -
Infectious Disease Clinics of North... Jun 2021Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised,... (Review)
Review
Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised, including patients with hematological malignancies and solid organ transplant recipients. Early recognition of infection is critical for treatment success, followed by prompt initiation of antifungal therapy with lipid formulation amphotericin B. Posaconazole and isavuconazole should be used for stepdown and salvage therapy. Surgical debridement is key for tissue diagnosis and treatment and should be pursued urgently whenever possible. In addition to surgery and antifungal therapy, reverting the underlying risk factor for infection is important for treatment response.
Topics: Antifungal Agents; Diabetes Mellitus, Type 2; Humans; Immunocompromised Host; Mucorales; Mucormycosis
PubMed: 34016285
DOI: 10.1016/j.idc.2021.03.009 -
Medical Mycology Apr 2018The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common... (Review)
Review
The diagnosis and treatment of mucormycosis are challenging. The incidence of the disease seems to be increasing. Hematological malignancies are the most common underlying disease in countries with high income and uncontrolled diabetes in developing countries. Clinical approach to diagnosis lacks sensitivity and specificity. Radiologically, multiple (≥10) nodules and pleural effusion are reportedly associated with pulmonary mucormycosis. Another finding on computerized tomography (CT) scan, which seems to indicate the presence of mucormycosis, is the reverse halo sign. Microscopy (direct and on histopathology) and culture are the cornerstones of diagnosis. Molecular assays can be used either for detection or identification of mucormycetes, and they can be recommended as valuable add-on tools that complement conventional diagnostic procedures. Successful management of mucormycosis is based on a multimodal approach, including reversal or discontinuation of underlying predisposing factors, early administration of active antifungal agents at optimal doses, complete removal of all infected tissues, and use of various adjunctive therapies. Our armamentarium of antifungals is slightly enriched by the addition of two newer azoles (posaconazole and isavuconazole) to liposomal amphotericin B, which remains the drug of choice for the initial antifungal treatment, according to the recently published guidelines by ECIL-6, as well as those published by ECMM/ESCMID. Despite the efforts for better understanding of the pathogenesis, early diagnosis and aggressive treatment of mucormycosis, the mortality rate of the disease remains high.
Topics: Antifungal Agents; Combined Modality Therapy; Debridement; Diagnostic Imaging; Early Diagnosis; Humans; Microbiological Techniques; Molecular Diagnostic Techniques; Mucorales; Mucormycosis
PubMed: 29538730
DOI: 10.1093/mmy/myx101 -
Infection Oct 2021The recent emergence of the Coronavirus Disease (COVID-19) disease had been associated with reports of fungal infections such as aspergillosis and mucormycosis... (Review)
Review
BACKGROUND
The recent emergence of the Coronavirus Disease (COVID-19) disease had been associated with reports of fungal infections such as aspergillosis and mucormycosis especially among critically ill patients treated with steroids. The recent surge in cases of COVID-19 in India during the second wave of the pandemic had been associated with increased reporting of invasive mucormycosis post COVID-19. There are multiple case reports and case series describing mucormycosis in COVID-19.
PURPOSE
In this review, we included most recent reported case reports and case-series of mucormycosis among patients with COVID-19 and describe the clinical features and outcome.
RESULTS
Many of the mucormycosis reports were eported from India, especially in COVID-19 patients who were treated and recovered patients. The most commonly reported infection sites were rhino-orbital/rhino-cerebral mucormycosis. Those patients were diabetic and had corticosteroids therapy for controlling the severity of COVID-19, leading to a higher fatality in such cases and complicating the pandemic scenario. The triad of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), corticosteroid use and uncontrolled diabetes mellitus have been evident for significant increase in the incidence of angioinvasive maxillofacial mucormycosis. In addition, the presence of spores and other factors might play a role as well.
CONCLUSION
With the ongoing COVID-19 pandemic and increasing number of critically ill patients infected with SARS-CoV-2, it is important to develop a risk-based approach for patients at risk of mucormycosis based on the epidemiological burden of mucormycosis, prevalence of diabetes mellitus, COVID-19 disease severity and use of immune modulating agents including the combined use of corticosteroids and immunosuppressive agents in patients with cancer and transplants.
Topics: COVID-19; Humans; Mucormycosis; Pandemics; SARS-CoV-2; Superinfection
PubMed: 34302291
DOI: 10.1007/s15010-021-01670-1 -
Frontiers in Cellular and Infection... 2023Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in... (Review)
Review
Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.
Topics: Humans; Mucormycosis; Antifungal Agents; COVID-19; Mucorales; Diabetes Mellitus; Iron
PubMed: 37808914
DOI: 10.3389/fcimb.2023.1254919 -
Clinical Microbiology and Infection :... Jan 2019The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored.
OBJECTIVES
To examine the contemporary epidemiology, clinical manifestations, diagnosis and causative pathogens of mucormycosis.
DATA SOURCES
Ovid MEDLINE and Ovid EMBASE from January 2000 to January 2017.
STUDY ELIGIBILITY CRITERIA
Published case reports/series of proven/probable mucormycosis.
PARTICIPANTS
Patients ≥18 years old.
METHODS
Patient characteristics, disease manifestations and causative pathogens were summarized descriptively. Categorical variables were assessed by chi-square test or Fischer's exact test, and continuous variables by the Wilcoxon-Mann-Whitney or Kruskal-Wallis test. Risk factors for the different clinical manifestations of mucormycosis were identified using multivariate logistic regression.
RESULTS
Initial database searches identified 3619 articles of which 600 (851 individual patient cases) were included in the final analysis. Diabetes mellitus was the commonest underlying condition (340/851, 40%) and was an independent risk for rhino-orbital-cerebral mucormycosis (odds ratio (OR) 2.49; 95% CI 1.77-3.54; p < 0.001). Underlying haematological malignancy was associated with disseminated infection (OR 3.86; 95% CI 1.78-8.37; p 0.001), whereas previous solid organ transplantation was associated with pulmonary (OR 3.19; 95% CI 1.50-6.82; p 0.003), gastrointestinal (OR 4.47; 95% CI 1.69-11.80; p 0.003), or disseminated (OR 4.20; 95% CI 1.68-10.46; p 0.002) mucormycosis. Eight genera (24 species) of Mucorales organisms were identified in 447/851 (53%) cases, of which Rhizopus spp. (213/447, 48%) was the most common. Compared with other genera, Rhizopus spp. was predominantly observed in patients with rhino-orbital-cerebral mucormycosis (75/213, 35% versus 34/234, 15%; p < 0.001). Death was reported in 389/851 (46%) patients. Mortality associated with Cunninghamella infections was significantly higher than those caused by other Mucorales (23/30, 71% versus 185/417, 44%; p < 0.001). However, Cunninghamella spp. were isolated primarily in patients with pulmonary (17/30, 57%) or disseminated disease (10/30, 33%).
CONCLUSIONS
Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.
Topics: Diabetes Mellitus; Hematologic Neoplasms; Humans; Mucorales; Mucormycosis; Rhizopus; Risk Factors
PubMed: 30036666
DOI: 10.1016/j.cmi.2018.07.011 -
Anais Brasileiros de Dermatologia 2017Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic patients... (Review)
Review
Cutaneous mucormycosis is an emerging fungal infection caused by opportunistic fungi of the phylum Glomeromycota. It is frequent in poorly controlled diabetic patients and individuals with immunosuppression. It is usually acquired by direct inoculation through trauma. The clinical presentation is nonspecific, but an indurated plaque that rapidly evolves to necrosis is a common finding. Diagnosis should be confirmed by demonstration of the etiological agent and new molecular diagnostic tools have recently been described. It is an invasive life-threatening disease and in order to improve survival, a prompt diagnosis and multidisciplinary management should be provided. The treatment of choice is amphotericin B, but new azoles, such as posaconazole and isavuconazole, must be considered.
Topics: Antifungal Agents; Dermatomycoses; Humans; Mucormycosis
PubMed: 29186239
DOI: 10.1590/abd1806-4841.20176614 -
Clinical Microbiology Reviews Oct 2018The pathogenic entomophthoralean fungi cause infection in insects and mammalian hosts. and species can be found in soil and insect, reptile, and amphibian droppings in... (Review)
Review
The pathogenic entomophthoralean fungi cause infection in insects and mammalian hosts. and species can be found in soil and insect, reptile, and amphibian droppings in tropical and subtropical areas. The life cycles of these fungi occur in these environments where infecting sticky conidia are developed. The infection is acquired by insect bite or contact with contaminated environments through open skin. typically causes chronic rhinofacial disease in immunocompetent hosts, whereas some species can be found in immunocompromised patients. infection is restricted to subcutaneous tissues but may be involved in intestinal and disseminated infections. Its early diagnosis remains challenging due to clinical similarities to other intestinal diseases. Infected tissues characteristically display eosinophilic granulomas with the Splendore-Höeppli phenomenon. However, in immunocompromised patients, the above-mentioned inflammatory reaction is absent. Laboratory diagnosis includes wet mount, culture serological assays, and molecular methodologies. The management of entomophthoralean fungi relies on traditional antifungal therapies, such as potassium iodide (KI), amphotericin B, itraconazole, and ketoconazole, and surgery. These species are intrinsically resistant to some antifungals, prompting physicians to experiment with combinations of therapies. Research is needed to investigate the immunology of entomophthoralean fungi in infected hosts. The absence of an animal model and lack of funding severely limit research on these fungi.
Topics: Antifungal Agents; Entomophthorales; Humans; Zygomycosis
PubMed: 30158298
DOI: 10.1128/CMR.00014-18 -
Clinical Microbiology and Infection :... Oct 2009The prevalence of cutaneous and soft tissue zygomycosis appears to have increased in recent years. We reviewed 78 case reports of cutaneous zygomycosis published from... (Review)
Review
The prevalence of cutaneous and soft tissue zygomycosis appears to have increased in recent years. We reviewed 78 case reports of cutaneous zygomycosis published from 2004 through 2008. Most patients with cutaneous zygomycosis have underlying conditions such as haematological malignancies, diabetes mellitus or solid organ transplantation, but a large proportion of them are immunocompetent. Trauma is the most common predisposing factor leading to zygomycosis in immunocompetent patients. If the patient is immunocompromised, the infection may disseminate. Cutaneous zygomycosis may be localized, may extend to deep underlying tissues, or may be disseminated. The most common clinical presentation is induration of the skin with surrounding erythema, rapidly progressing to necrosis. Histological examination and culture of soft tissue are important for the diagnosis of cutaneous zygomycosis. Treatment consists of surgical debridement, administration of antifungal agents (amphotericin B formulations and/or posaconazole) and, occasionally, hyperbaric oxygen. Mortality rates are approximately 30%.
Topics: Antifungal Agents; Debridement; Dermatomycoses; Humans; Immunocompromised Host; Risk Factors; Wounds and Injuries; Zygomycosis
PubMed: 19754756
DOI: 10.1111/j.1469-0691.2009.02979.x -
Jornal Brasileiro de Pneumologia :... 2010Zygomycosis (mucormycosis) is a rare but highly invasive infection caused by fungi belonging to the order Mucorales, which includes the genera Rhizopus, Mucor,... (Review)
Review
Zygomycosis (mucormycosis) is a rare but highly invasive infection caused by fungi belonging to the order Mucorales, which includes the genera Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces and Syncephalastrum. This type of infection is usually associated with hematologic diseases, diabetic ketoacidosis and organ transplantation. The most common form of presentation is rhinocerebral mucormycosis, with or without pulmonary involvement. Pulmonary zygomycosis is more common in patients with profound, prolonged neutropenia and can present as segmental or lobar infiltrates, isolated nodules, cavitary lesions, hemorrhage or infarction. The clinical and radiological manifestations are often indistinguishable from those associated with invasive aspergillosis. This article describes the general characteristics of pulmonary zygomycosis, emphasizing laboratory diagnosis, and illustrates the morphology of some lesions.
Topics: Diagnosis, Differential; Diagnostic Techniques, Respiratory System; Humans; Lung Diseases, Fungal; Pulmonary Aspergillosis; Zygomycosis
PubMed: 20209316
DOI: 10.1590/s1806-37132010000100018