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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 -
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 -
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 :... Jun 2023Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic.
OBJECTIVES
To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis.
METHODS OF DATA SYNTHESIS
Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality.
DATA SOURCES
PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.
STUDY ELIGIBILITY CRITERIA
Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022.
PARTICIPANTS
Adults who developed mucormycosis during or after COVID-19.
INTERVENTIONS
Patients with and without individual clinical variables were compared.
ASSESSMENT OF RISK OF BIAS
Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies.
RESULTS
Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780).
CONCLUSION
Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.
Topics: Adult; Humans; Aged; Mucormycosis; Coinfection; Pandemics; COVID-19; Hospitalization
PubMed: 36921716
DOI: 10.1016/j.cmi.2023.03.008 -
Journal of Microbiology, Immunology,... Jun 2023COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the... (Review)
Review
COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10-15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.
Topics: Humans; Mucormycosis; Pandemics; COVID-19; Fungi; Pulmonary Aspergillosis
PubMed: 36586744
DOI: 10.1016/j.jmii.2022.12.004 -
Clinical Infectious Diseases : An... Sep 2022Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of...
BACKGROUND
Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis.
METHODS
We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus.
RESULTS
The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0-9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, -2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03-.73], P = .02).
CONCLUSIONS
Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR.
Topics: Amphotericin B; Antifungal Agents; Early Detection of Cancer; Humans; Mucorales; Mucormycosis; Polymerase Chain Reaction; Prospective Studies
PubMed: 34986227
DOI: 10.1093/cid/ciab1066 -
International Journal of Infectious... Jul 2021
Topics: Humans; Mucormycosis; Nose; Zygomycosis
PubMed: 34091002
DOI: 10.1016/j.ijid.2021.05.081 -
Journal of Indian Prosthodontic Society 2021
Topics: Disease Management; Humans; Mucormycosis; Prosthodontics
PubMed: 34810358
DOI: 10.4103/jips.jips_436_21 -
CMAJ : Canadian Medical Association... Sep 2021
Topics: Antifungal Agents; Diabetes Mellitus, Type 2; Female; Humans; Middle Aged; Mucormycosis; Oral Ulcer; Palate, Hard
PubMed: 34544793
DOI: 10.1503/cmaj.211026-f