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måndag 13 mars 2023

Savon Sanomissa 2014 hyvä kirjoitus maailman sienistä ja homeista


Sienten myrkkyjä voidaan hyödyntää

Kosteushome Aspergillus fumigatus ja muut yhtymäsienet Mucorales spp. ja Fusarium spp.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827224/

2021 Jan; 7(1): 40.
Published online 2021 Jan 9. doi: 10.3390/jof7010040
PMCID: PMC7827224
PMID: 33435452

Filamentous Fungal Infections in a Tertiary Care Setting: Epidemiology and Clinical Outcome


Abstract

Information on the distribution of filamentous fungal pathogens, which cause potential life-threatening invasive infections mostly in immunocompromised persons, is of great importance. The aim of this study was to evaluate the epidemiology and clinical outcome in patients with infections due to filamentous fungi at the University Hospital of Vienna, Austria. We conducted a retrospective observational study and consecutively included patients of any age with filamentous fungal infections between 2009 and 2017. The classification for probable and proven invasive filamentous fungal infections was based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC) criteria or the expert opinion of an experienced clinical mycologist. We included 129 patients (median age: 52 years; 47.3% female) with episodes of 101 proven and probable invasive and 35 localized filamentous fungal infections (16 sinus, 14 eye, one ear, and four deep cutaneous). Aspergillus fumigatus alone accounted for 50.3% of the fungi, which was followed by the Mucorales group (13.7%) and Fusarium spp. (8.5%). Diagnosis was mainly based on culture findings. The lung was the most frequent site of infection. The 30-day and 90-day overall mortality of invasive fungal infections was 30.2% and 42.7%, respectively. We observed a high all-cause mortality among patients with invasive filamentous fungal infections. Prospective data collection in a nationwide registry would be necessary to provide important information on surveillance to clinicians and other decision-makers.

Keywords: filamentous fungi, invasive fungal infections, mold infections

 

Homesieniluokka MUCORALES , entinen nimi Zygomycetes,.Perustavaa lisätietoa oppikirjasta

 

MUCORALES


Hyaline Molds, Mucorales (Zygomycetes), Dermatophytes, and Opportunistic and Systemic Mycoses

Published on 08/02/2015 by admin

Filed under Basic Science

Last modified 08/02/2015


https://clinicalgate.com/hyaline-molds-mucorales-zygomycetes-dermatophytes-and-opportunistic-and-systemic-mycoses

Chapter 6

Hyaline Molds, Mucorales (Zygomycetes), Dermatophytes, and Opportunistic and Systemic Mycoses

Objectives

1. Describe where mucorales (zygomycetes) are found, how they are transmitted to humans, and the diseases they cause.

2. Describe the characteristic colony morphology of the mucorales (zygomycetes).

MUCORMYCETES (2014) Näissä filamenttihomeissa on Mucormycosis- taudinaihauttajia.

 Artikkelin kirjoittamisen aikaan 2014  mainittiin,  että MUCORMYKOOSI osoitti lisääntymistrendiä  jo silloin. Sitä on esiintynyt nyt  Covid-19 pandemian sekundäärisenä ilmiönä   kymmenintuhansin tapauksin Intiassa ja korkean mortaliteetin takia sen  tehokkaan  lääkityksen löytö   ja hoito on tärkeää. Sairaanhoidollinen  järjestelmä on sen takia ollut  suuressa rasituksessa.


MUCORMYCETES lajit

Ihmiselle mucormykoosia aiheuttavista on tehty Intiasa tutkimus ja tässä artikkelissa on 80 lajiesimerkkiä.

https://onlinelibrary.wiley.com/doi/10.1111/myc.12234

13.3.2023


 

MUCORALES Ihmiselle invasiivia mucormykoosia aihettavia homesieniä

 Terveen ihmisen immuunovaste pärjäilee  luonnon sieni-  ja homeluokan mikrobeja vastaan. Kuitenkin Covidpandemian aikana on  esim mukormykoosin määrä paikoitellen maailmassa kovasti noussut. 


MUCORMYCOSIS artikkeleita ENNEN post-covid-jaksoa (1.1-1.6) ja Covid-19 pandemian aikaan (2.1.- 2.5) . Koottu 13.3.2023


1.1. Vuosi 2020 MUCORMYCOSIS

Homesieniluokka:   MUCORALES, filamentous molds

. 2020 Feb;41(1):99-114.

doi: 10.1055/s-0039-3401992. Epub 2020 Jan 30. Mucormycosis

Gail Reid  1 Joseph P Lynch 3rd  2 Michael C Fishbein  3 Nina M Clark  1

Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result from ingestion of contaminated food, inhalation of spores into the nares or lungs, or inoculation into disrupted skin or wounds. In developed countries, mucormycosis occurs primarily in severely immunocompromised hosts (e.g., those with hematological malignancies, organ transplantation, neutropenia, autoimmune disorders, or other impairments in immunity). Only 6 to 10% of cases occur in subjects with no underlying disease. In contrast, in developing countries, most cases of mucormycosis occur in persons with poorly controlled diabetes mellitus or in immunocompetent subjects following trauma. Mucormycosis exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis, and infarction of tissue. Mortality associated with invasive mucormycosis is high (> 30-50%), with 90% mortality associated with disseminated disease. Mortality rates are much lower, though still significant (10-30%), among patients with localized cutaneous disease.The diagnosis of mucormycosis relies upon histopathology and culture. Blood tests are of limited diagnostic value. Even with disseminated disease, blood cultures are usually negative. Mucorales have a distinct histological appearance, with irregular, nonseptate hyphae that branch at right angles. Cultures and/or polymerase chain reaction (PCR) are important to identify the genera.Based on anatomic localization, mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal (GI), (5) disseminated, and (6) mucormycosis of uncommon sites. Among diabetics, ROCM is the most common clinical presentation, whereas lung involvement is uncommon. In contrast, among organ transplant recipients or patients with hematological malignancies (HemeM), pulmonary and disseminated diseases are most common. Mucormycosis can progress rapidly, and delay in initiation of treatment by even a few days markedly worsens outcomes.Due to the rarity of mucormycosis, randomized controlled therapeutic trials have not been performed. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but the newer triazoles, posaconazole (POSA) and isavuconazole (ISAV) (the active component of the prodrug isavuconazonium sulfate), may be effective in patients refractory to or intolerant of LFAB. Early surgical debridement or excision plays an important adjunctive role. Additional studies are required to assess the optimal duration of therapy as well as the specific roles of LFAB and the triazoles in the treatment of mucormycosis.

1.2 Vuosi 2015. MUCORMYCOOSI, insidenssi nousussa, mortaliteetti 50%. Diffidg:Aspergilloosi

Mucormycosis: New Developments into a Persistently Devastating Infection. Danion F, Aguilar C, Catherinot E, Alanio A, DeWolf S, Lortholary O, Lanternier F. Semin Respir Crit Care Med. 2015 Oct;36(5):692-705. doi: 10.1055/s-0035-1562896. Epub 2015 Sep 23. PMID: 26398536 Review. DOI: 10.1055/s-0035-1562896 Abstract

Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.

1.3. Vuosi 2013. Ihon mukormykoosi, Kutaani mukormykoosi. Mortaliteetti 4%-10%, jos tauti on lokalisoitunut.

Cutaneous mucormycosis. Skiada A, Petrikkos G. Skinmed. 2013 May-Jun;11(3):155-9; quiz 159-60. PMID: 23930354 Review. Abstract

Mucormycosis is an invasive fungal infection caused by fungi of the order Mucorales, mainly affecting immunocompromised patients. Cutaneous mucormycosis is the third most common clinical form of the disease, after pulmonary and rhino-cerebral. The usual factors predisposing to this infection are hematological malignancies and diabetes mellitus, but a significant proportion of patients are immunocompetent. The agents of mucormycosis are ubiquitous in nature and are transmitted to the skin by direct inoculation, as a result of various types of trauma. These include needle sticks, stings and bites by animals, motor vehicle accidents, natural disasters, and burn injuries. The typical presentation of mucormycosis is the necrotic eschar, but it can present with various other signs. The infection can be locally invasive and penetrate into the adjacent fat, muscle, fascia, and bone, or become disseminated. Diagnosis is difficult because of the nonspecific findings of mucormycosis. Biopsy and culture should be performed. The treatment of mucormycosis is multimodal and consists of surgical debridement, use of antifungal drugs (amphotericin B and posaconazole), and reversal of underlying risk factors, when possible. Mortality rates, although lower than in other forms of the disease, are significant, ranging from 4% to 10% when the infection is localized.

1.4. Vuosi 2016. Mukormykoosista katsaus. Terapiamahdollisuuksista.

Breaking the Mold: A Review of Mucormycosis and Current Pharmacological Treatment Options. Riley TT, Muzny CA, Swiatlo E, Legendre DP. Ann Pharmacother. 2016 Sep;50(9):747-57. doi: 10.1177/1060028016655425. Epub 2016 Jun 15. PMID: 27307416 Review. Abstract

Objective: To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. Data sources: An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. Study selection and data extraction: Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. Data synthesis: Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. Conclusion: Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B. Keywords: Mucorales; amphotericin B; isavuconazole; posaconazole.


1.5. Vuonna 2009 ei-fataali, kuitenkin levinnyt(disseminoitunut) mukormykoosi yksittäisessä elinsiirteessä.

French. [Non-fatal disseminated mucormycosis in a solid organ transplant] C Minet  1 A BonadonaA TabahA KarkasL MescamC SchwebelR HamidfarC PisonC Saint-RaymondO FaureD SalameireJ-F Timsit DOI: 10.1016/s0761-8425(09)73337-6 Abstract Background: Mucormycosis is a rare fungal infection occurring most frequently in immunocompromised patients. The pathogens are filamentous fungi, order of Mucorales. Disseminated mucormycosis is a severe, life treating disease. Early diagnosis is a major determinant for prognosis, however, it remains difficult. The management consists in an early antifungal therapy using lipid formulation of amphotericin B associated with an extensive surgical debridement. Despite this therapeutic of choice, the mortality of disseminated mucormycosis remains high. Observation: We report the case of disseminated mucormycosis in a 25 years old woman 9 months after a pulmonary transplantation. The clinical presentation included pulmonary and thyroid localization and the pathogen was Absidia corymbifera. The patient survived thanks to a large surgical debridement, and an early antifungal bitherapy by lipid formulation of amphotericin B and posaconazole. Conclusion: The re-emergence and the high mortality of mucormycosis in solid organ transplant receiver show the necessity to find new therapeutic approaches. Posaconazole associated with liposomal amphotericin B could be an interesting option to treat disseminated mucormycosis and improve their outcome.

1.6. Vuonna 2011 Keuhkojen mukormykoosi. Aspergilloosiin vaikuttavat antifungaalit eivät tehoa mukormykoosiin.

Pulmonary mucormycosis. Hamilos G, Samonis G, Kontoyiannis DP. Semin Respir Crit Care Med. 2011 Dec;32(6):693-702. doi: 10.1055/s-0031-1295717. Epub 2011 Dec 13. PMID: 22167397 Review. DOI: 10.1055/s-0031-1295717 Abstract Mucormycosis (formerly zygomycosis) is a life-threatening opportunistic mycosis that infects a broad range of hosts with qualitative or quantitative defects in innate immunity, including patients with severe neutropenia, recipients of corticosteroids or other immunosuppressive medications, poorly controlled diabetes mellitus, and those with iron overload states. Mucormycosis has recently emerged as breakthrough sinopulmonary infection in hematologic patients and recipients of transplantation being on antifungal prophylaxis with Aspergillus-active antifungals that lack activity against Mucorales. Unlike pulmonary aspergillosis, the prognosis and outcome of pulmonary mucormycosis have not improved significantly over the last decade, mainly because of difficulties in early diagnosis and the limited activity of current antifungal agents against Mucorales. Recent evidence suggests a critical role for iron metabolism and fungal-endothelial cell interactions in pathogenesis of mucormycosis, and holds promise for development of novel therapeutic strategies. Currently, prompt initiation of antifungal therapy with a lipid amphotericin B-based regimen, reversal of underlying host factors, and aggressive surgical approach offers the best chances for survival of patients infected with this devastating mycosis.

1.7.



Covid 19 -pandemian aikaisia artikkeleita mukormykoosista

2. 1. Vuonna2023 , tammikuussa. Mukormykoosi COVID 19:ssa mainitaan (diabetes+ corticosteroidi +covid19 )

cotH Genes Are Necessary for Normal Spore Formation and Virulence in Mucor lusitanicus. Szebenyi C, Gu Y, Gebremariam T, Kocsubé S, Kiss-Vetráb S, Jáger O, Patai R, Spisák K, Sinka R, Binder U, Homa M, Vágvölgyi C, Ibrahim AS, Nagy G, Papp T. mBio. 2023 Feb 28;14(1):e0338622. doi: 10.1128/mbio.03386-22. Epub 2023 Jan 10. PMID: 36625576 Free PMC article. DOI: 10.1128/mbio.03386-22 ABSTRACT Mucormycosis is an invasive fungal infection caused by certain members of the fungal order of Mucorales. The species most frequently identified as the etiological agents of mucormycosis belong to the genera Rhizopus, Lichtheimia, and Mucor. The frequency of systemic mucormycosis has been increasing, mainly because of increasing numbers of susceptible patients. Furthermore, Mucorales display intrinsic resistance to the majority of routinely used antifungal agents (e.g., echinocandins and short-tailed azoles), which limits the number of possible therapeutic options. All the above-mentioned issues urge the improvement of molecular identification methods and the discovery of new antifungal targets and strategies. Spore coat proteins (CotH) constitute a kinase family present in many pathogenic bacteria and fungi and participate in the spore formation in these organisms. Moreover, some of them can act as virulence factors being receptors of the human GRP78 protein during Rhizopus delemar-induced mucormycosis. We identified 17 cotH-like genes in the Mucor lusitanicus genome database. Successful disruption of five cotH genes in Mucor was performed using the CRISPR-Cas9 system. The CotH3 and CotH4 proteins play a role in adaptation to different temperatures as well as in developing the cell wall structure. We also show CotH4 protein is involved in spore wall formation by affecting the total chitin content and, thus, the composition of the spore wall. The role of CotH3 and CotH4 proteins in virulence was confirmed in two invertebrate models and a diabetic ketoacidosis (DKA) mouse model. IMPORTANCE Current treatment options for mucormycosis are inadequate, resulting in high mortality rates, especially among immunosuppressed patients. The development of novel therapies for mucormycosis has been hampered by lack of understanding of the pathogenetic mechanisms. The importance of the cell surface CotH proteins in the pathogenesis of Rhizopus-mediated mucormycosis has been recently described. However, the contribution of this family of proteins to the virulence of other mucoralean fungi and their functionality in vital processes remain undefined. Through the use of the CRISPR-Case9 gene disruption system, we demonstrate the importance of several of the CotH proteins to the virulence of Mucor lusitanicus by using three infection models. We also report on the importance of one of these proteins, CotH4, to spore wall formation by affecting chitin content. Therefore, our studies extend the importance of CotH proteins to Mucor and identify the mechanism by which one of the CotH proteins contributes to the development of a normal fungal cell wall, thereby indicating that this family of proteins can be targeted for future development of novel therapeutic strategies of mucormycosis. INTRODUCTION Mucormycosis is a life-threatening opportunistic fungal infection caused by several members of the order Mucorales (1). Rhizopus, Lichtheimia, and Mucor species have most often been isolated from such infections as the causative agents (26). These invasive infections, which can manifest as rhino-orbito-cerebral, pulmonary, gastrointestinal, cutaneous, or disseminated diseases, are known for their aggressive progression and high mortality rates (i.e., 30 to 90%, depending on the manifestation, the underlying condition of the patient, and the therapy) (5, 7, 8). They most frequently occur in patients with an immunocompromised status due to immunosuppression (i.e., primarily for solid organ or hematopoietic stem cell transplantation) or hematological malignancies. Uncontrolled diabetes (with or without ketoacidosis), elevated levels of free iron in the blood, and severe trauma can also be risk factors for mucormycosis (6, 7, 9, 10). The frequency of systemic mucormycosis has been increasing, mainly because of the increasing numbers of susceptible populations. Furthermore, Mucorales fungi display intrinsic resistance to the majority of routinely used antifungal agents (e.g., echinocandins and short-tailed azoles), which also limits the number of possible therapeutic options (4, 11). Recently, an increasing number of mucormycosis cases have been reported among COVID-19 patients treated with corticosteroids and with underlying diabetes (1214).

Spore coat protein H (CotH) was first discovered in the endospore-forming bacterium Bacillus subtilis where it participates in the formation of the endospore coat (15). It proved to be an atypical protein kinase, which has an essential role in endospore formation by phosphorylating other structural proteins, such as CotB and CotG. Knockout of the encoding cotH gene had a pleiotropic effect on the structure of the outer spore coat, as well as the development of a germination-deficient phenotype (1618).

CotH proteins not only occur in endospore-forming bacteria but also are present in many Mucoromycota species, such as Mucor lusitanicus, Lichtheimia corymbifera, Cunninghamella bertholletiae, Rhizopus delemar, Saksanaea vasiformis, Syncephalastrum monosporum, Mortierella alpina, and Umbelopsis isabellina (19, 20). In the mucormycosis-causing species R. delemar (synonym R. oryzae), several CotH proteins, including CotH1 (RO3G_05018 [EIE80313.1]), CotH2 (RO3G_08029 [EIE83324.1]), CotH3 (RO3G_11882 [EIE87171.1]), CotH4 (RO3G_09277 [EIE84567.1]), CotH5 (RO3G_01139 [EIE76435.1]), CotH6 (IGS-990-880_03186), CotH7 (IGS-990-880_09445), and CotH8 (IGS-990-880_11474), were previously identified (20, 21). Among them, CotH2 and CotH3 were found to mediate the interaction of the fungus with the glucose-regulated protein 78 (GRP78) expressed on the surface of endothelial cells (19), while CotH7 was found to mediate invasion of alveolar epithelial cells via interaction with integrin α3β1 (22). This interaction proved to be crucial for the fungal invasion of the host. Specifically, the level of GRP78 molecules significantly increases in sinuses and lungs during diabetic ketoacidosis (DKA), causing vulnerability toward the fungal infection (23). Moreover, IgG antibodies produced against a peptide of Rhizopus CotH3 protein and conserved among CotH7 protein protected mice with DKA and neutropenia from mucormycosis (19). Thus, anti-CotH3 antibodies were proposed as promising candidates for immunotherapy of human mucormycosis (1). Finally, due to the universal presence of cotH genes in Mucorales and the lack of their presence in other pathogens, they proved to be appropriate biomarkers for diagnosis through a PCR-based assay allowing fungal DNA detection in human urine samples (24).

M. lusitanicus (formerly Mucor circinelloides f. lusitanicus) (25) is a frequently used model organism for studying morphogenesis and pathogenesis of mucormycosis (2631). In the genome of this fungus, we found 17 possible cotH genes, of which the function and role in the pathogenicity or other mechanisms are yet unknown. This high number of genes lets us consider the possibility that the CotH family may be a diverse group of proteins having a role in various biological processes. The present study aimed to investigate the function and possible role in pathogenicity of five cotH genes of M. lusitanicus.

2.2. Vuonna 2022. Sienten ja homeitten vastainen immuunipuolustus on puuttellinen COVID-19-potilaissa.

Defective antifungal immunity in patients with COVID-19. Morton CO, Griffiths JS, Loeffler J, Orr S, White PL. Front Immunol. 2022 Nov 30;13:1080822. doi: 10.3389/fimmu.2022.1080822. eCollection 2022. PMID: 36531987 Free PMC article. Review. See this image and copyright information in PMC Figure 1 A graphical summary demonstrating how COVID-19 infection contributes to increased susceptibility to invasive fungal disease.Abstract

The COVID-19 pandemic has placed a huge strain on global healthcare and been a significant cause of increased morbidity and mortality, particularly in at-risk populations. This disease attacks the respiratory systems and causes significant immune dysregulation in affected patients creating a perfect opportunity for the development of invasive fungal disease (IFD). COVID-19 infection can instill a significant, poorly regulated pro-inflammatory response. Clinically induced immunosuppression or pro-inflammatory damage to mucosa facilitate the development of IFD and Aspergillus, Mucorales, and Candida infections have been regularly reported throughout the COVID-19 pandemic. Corticosteroids and immune modulators are used in the treatment of COVID-19. Corticosteroid use is also a risk factor for IFD, but not the only reason for IFD in COVID -19 patients. Specific dysregulation of the immune system through functional exhaustion of Natural killer (NK) cells and T cells has been observed in COVID-19 through the expression of the exhaustion markers NK-G2A and PD-1. Reduced fungicidal activity of neutrophils from COVID-19 patients indicates that immune dysfunction/imbalance are important risk factors for IFD. The COVID-19 pandemic has significantly increased the at-risk population for IFD. Even if the incidence of IFD is relatively low, the size of this new at-risk population will result in a substantial increase in the overall, annual number of IFD cases. It is important to understand how and why certain patients with COVID-19 developed increased susceptibility to IFD, as this will improve our understanding of risk of IFD in the face of future pandemics but also in a clinical era of increased clinical immuno-suppression/modulation. Keywords: COVID-19; antifungal immunity; aspergillosis; candidiasis; immune exhaustion; invasive fungal disease; mucormycosis. ‘



2.3. Vuonna 2022. Kliinisistä tutkimuksista katsaus isavukonatsolin (ISA) tehosta invasiivisissa mykooseissa(IFD). ISA on uusi antifungaali.

Invasiivisen sienitaudin lääkehoidosta eräs valmiste ISA isavuconatsoli vaikuttaisi tehoavan (primääristi ja primäärihoidon de-eskalaatiossa ensisijaisena) useassa mykoosissa kuten invasiivisessa aspergilloosissa (IA), invasiivisessa mukormykoosissa (IM) ja invasiivisessa candidiaasissa (IC).

Clinical research advances of isavuconazole in the treatment of invasive fungal diseases. Zhang T, Shen Y, Feng S. Front Cell Infect Microbiol. 2022 Dec 1;12:1049959. doi:10.3389/fcimb.2022.1049959. eCollection 2022. PMID: 36530445 Free PMC article. Review. See this image and copyright information in PMC Figure 1 The chemical structure of ISA and its antifungal mechanism. Purpose: Invasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD. Methods: We performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review. Results: IFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD. Conclusion: Taken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions. Keywords: invasive aspergillosis; invasive candidiasis; invasive fungal diseases (IFD); invasive mucormycosis; isavuconazole. Copyright © 2022 Zhang, Shen and Feng.



2.4. Vuonna 2022. Immunokompetentin traumapotilaan mucormycoositulehdus hoidettu ja ISA-terapiaa käytetty. Tapauskuvaus.

Successful management of mucormycosis infection secondary to motor vehicle accident in a healthy adolescent: A case report. Shah H, Chisena E, Nguyen B, Tristram D, Bialowas C. Med Mycol Case Rep. 2022 Nov 2;38:36-40. doi: 10.1016/j.mmcr.2022.10.004. eCollection 2022 Dec. PMID: 36393995 Free PMC article. Abstract Mucormycosis in healthy adolescents is a rare etiology of infection that does not have a commonly known protocol for management. This report describes an adolescent male who developed soft tissue mucormycosis secondary to a motor vehicle accident with severe lower extremity injuries. Treatment involved topical amphotericin B washouts and beads, serial aggressive debridement, and isavuconazole. To our knowledge, this is one of few documented cases of successful lower extremity salvage in an immunocompetent adolescent infected with mucormycosis and treated with isavuconazole. Keywords: Immunocompetent; Limb salvage; Motor vehicle accident; Mucormycosis; Wound.


2.5. Vuonna 2022 Post Covid-19 Rhinokerebraalinen mukormykoosi. Tapauskuvaus.

Post COVID-19 rhinocerebral mucormycosis: a case report and literature review. El Korbi A, Bhar S, Bergaoui E, Harrathi K, Koubaa J. Pan Afr Med J. 2022 Jul 14;42:202. eCollection 2022. PMID: 36284570 Free PMC article. Review. See all "Cited by" articles DOI: 10.11604/pamj.2022.42.202.33690

Ear, Nose, and Throat (ENT), Fattouma Bourguiba Teaching Hospital, Monastir, Tunisia, Research Unit, Quality and Security of Care, University of Monastir, Monastir, Tunisia

 Abstract. The pandemic of coronavirus disease 2019 (COVID-19) still remains on an upsurge trend. The second and the waves of this disease have led to panic in many countries, and some parts of the world suffering from the fourth wave. In the midst of this pandemic, COVID-19 patients are acquiring secondary infections such as mucormycosis also known as “black fungus disease”. Mucormycosis is a serious, but rare opportunistic fungal infection that spreads rapidly, and hence prompt diagnosis and treatment are necessary to avoid mortality and morbidity rate. We report in this paper, a case of a diabetic patient who presented with bilateral nasal obstruction, anosmia, and frontal headache diagnosed with rhinocerebral mucormycosis developing after COVID-19 infection with a favorable outcome after a medico-surgical treatment. Through this case, we aim to aware patricians of this possible association and the importance of early diagnosis to optimize treatment outcomes. Introduction Mucormycosis is a rare life-threatening invasive fungal infection caused by mold fungi of the genus Mucor, Rhizopus, Rhizomucor and Absidia which belong to the Mucorales order of the zygomycetes class [1]. It was possibly first described by Friedrich Küchenmeister in 1855 [1]. The most common type was Rhizopus oryzae responsible for approximately 60% of mucormycosis cases in humans; and 90% of the rhinocerebral form [2]. Over this pandemic of coronavirus disease (COVID-19), we observed a worldwide increasing mucormycosis in COVID-19 infected patients. It is frequently observed in immunosuppressed patients, particularly with diabetes, hematological malignancy, and immunosuppressive and corticosteroid therapy. It is rarely seen in healthy individuals. Here we report a case of rhinocerebral mucormycosis developed after COVID-19 infection in a diabetic patient who presented with bilateral nasal obstruction, anosmia, and frontal headache. Through this case, we aim to aware patricians of this possible association and the importance of early diagnosis to optimize treatment outcomes. Patient and observation. Patient information: a 62-year-old male patient with a history of type 2 diabetes, hypertension and coronary artery disease was referred to our department for persistent nasal obstruction and frontal headache. Clinical findings: clinical exam found a frontal swelling associated with edema of the upper right eyelid (Figure 1). Nasal endoscopy showed the presence of pus in the middle meatuses and necrotic appearance of the middle turbinates (Figure 2). Timeline of current episode: in fact, the patient was hospitalized for COVID-19 infection the third of January 2021 then he was referred to an intensive care unit where he received a high-flow oxygen for thirteen days combined with corticosteroid therapy, then the patient was transferred to the pandemic ward and discharged the 29th of January after a stay of 14 days. The patient presented since leaving the hospital with bilateral nasal obstruction, anosmia and frontal headaches. He consulted an otolaryngologist doctor who referred the patient to our department on the sixth of March 2021. Diagnostic assessment: biopsy of the middle turbinate and microbiological sampling were performed, with a presumed diagnosis of mucormycosis. Paranasal sinus computed tomography (CT) revealed pansinusitis with frontal osteitis and bone sequester surrounded by soft tissue edema (Figure 3). A cerebral magnetic resonance imaging (MRI) showed a frontal meningeal contrast enhancement without intracranial collection. Diagnosis: the diagnosis of mucormycosis was confirmed on histopathologic and direct microscopy examination of the specimen that showed typical Mucorales hyphae. Whereas, culture was not contributed in the specie identification. Therapeutic interventions: intravenous liposomal amphotericin B at the dose of 5 mg/kg/day was started early and debridement of the infection site was done. The antifungal treatment was extended for two months. Follow-up and outcome of interventions: during the hospitalization, the patient refused to take treatment for three days explained to side effects such as hypokalemia and vomiting that were corrected by an intravenous supplementation, and the antifungal was reintroduced. After one month, an improvement of nasal symptoms and headache with the regression of the frontal swelling were observed. However, the post-therapeutic MRI showed stability of the radiological findings. The patient was discharged after a clinical improvement. After a follow-up of seven months, we noted the persistence of the frontal swelling without any other sign. Nasal endoscopy did not show any sign of mucosa necrosis. Patient perspective: globally, despite the problem of antifungals intolerance, the patient showed satisfaction with his pathology´s care, and he adhered perfectly to the follow-up. Informed consent: written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review.

 Discussion: Two thousand twenty (2020) is a memorable, devastating year for global health, as an uncommon virus raced worldwide, emerging rapidly. It is one of the top killers, laying bare the inadequacies of the health systems. Today, worldwide health services are struggling to tackle COVID-19 and provide people with vital care. As the global COVID-19 pandemic enters the third year, countries around the world are racing to vaccinate their populations as novel variants emerge. In the midst of this pandemic; the COVID-19 patients are acquiring secondary infections such as mucormycosis also known as “black fungus disease” [1]. Habitually, mucormycosis is a rare, opportunistic life-threatening fungal disease. However, with COVID-19 infection, we have seen an explosion of cases. In fact, in March 2021, only 41 cases of mucormycosis associated with COVID-19 infection have been reported worldwide and 70% were from India [1], contrasting with more than 47,000 cases reported in India from May to July 2021 [3]. Rhino-orbital and rhino-orbito-cerebral forms were the most common presentations. Patel et al. [4], reports in their multicenter epidemiologic study a predominance of rhino-orbital mucormycosis associated with COVID-19 with 62.6% of cases followed by rhino-orbito-cerebral (ROC) in 23.5% and pulmonary form in 8.6% [3]. The main mode of transmission of mucormycosis is the inhalation of spores, ingestion of contaminated food and inoculation of the fungi into abrasions or cuts on the skin [1]. In healthy people, mononuclear and polymorphonuclear phagocytes eliminate fungal spores and hyphae [5], which is not the case of immunocompromised patients. A recent meta-analysis of 600 publications reported as major risk factors of mucormycosis: diabetes mellitus, trauma, hematological malignancies, diabetic ketoacidosis, neutropenia and prolonged corticosteroid therapy [6]. In the particular context of COVID-19 in infected patients, we observed an immune dysregulation with reduced numbers of T lymphocytes, CD4+T, and CD8+T cells that compromise innate immunity and enhance the risk of invasive fungal occurrence [7]. This risk is majored by the use of corticosteroid medications that magnify the effect of hyperglycemia in an eventual preexisting diabetic, and mechanical ventilation that contribute to inhalation of spores in immunocompromised individuals [1,8]. Moreover, cytokines released during COVID-19 increases intracellular iron and leakage of iron into the circulation, leading to high ferritin levels that permit the growth of Mucorales [3

In our case, diabetes and corticosteroids firstly prescribed to manage the COVID-19 pulmonary disease were the risk factors of mucormycosis coinfection. Clinical manifestations depend on the extension of a disease. The symptoms of rhino-orbital mucormycosis are similar to complicated rhinosinusitis with nasal obstruction, headache, facial pain, bloody nasal discharge, swelling of periorbital tissues, orbital cellulitis, chemosis, proptosis, blurry vision, and local eschar that is explained by a propensity of blood vessels invasion by Mucorales leading to thrombosis, ischemia and tissue necrosis [9-11]. Intracranial involvement may manifests neurological signs or altered mental status [9]. Mucormycosis is usually suspected based on results of direct microscopy of clinical specimens and confirmed the diagnosis on histological features when showing tissue invasion by non-pigmented hyphae in tissue sections stained with haematoxylin-eosin [12]. Culture are recommended for genus and species identification, not for diagnosis [12]. In the study of Patel et al. [4], mucormycosis diagnosis was made by direct microscopy in 82.6% of patients and histopathology in 90.5%. Culture identified the etiologic pathogen in 4<8.1% of cases [4]. In our case, the diagnosis was made on microscopy and histopathology constitutions, however the culture was not able to identify the specie of the Mucorales. Refer to the 2019 global guidelines for the diagnosis and treatment of mucormycosis published by the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and research Consortium, the treatment of mucormycosis is based on early and complete surgical debridement of the infected area associated with a systemic antifungal drugs [12]. Mucorales are resistant to many antifungal agents. The most active ones are liposomal amphotericin B (LAB) and triazoles (isavuconazole and posaconazole), thus they are considered as first-line therapy in mucomycosis [5]. The recommended dose of LAB is 5 mg/kg per day in cases of non-central nervous system involvement [12]. Otherwise, a prescription of high dose of LAB at 10 mg/kg/day could be supported in cases of intracranial invasion [12]. Triazoles are reported to be more frequently used in patients with COVID-19 associated mucormycosis than those with isolated mucormycosis [4]. The duration of treatment with active antifungal agents has not been determined, in general weeks to months of therapy are given [12,13]. The mortality rate of mucormycosis is about 50% [1]. In their study, comparing mucormycosis associated with COVID-19 to isolated mucormycosis, Patel et al. p2 found similar mortality rates in both groups. In our case, we observed favorable outcomes after a follow-up of seven months. Conclusion Through our case, we highlight the possibility of invasive secondary fungal infections in patients with COVID-19 infection. Physicians should be aware of early symptoms of mucormycosis to enable prompt diagnosis and adequate treatment to avoid as possible as can bad outcomes. MeSH terms Antifungal Agents / therapeutic use; Combined Modality Therapy ; Debridement / methods ; Humans ; Lung Diseases, Fungal / diagnosis* ; Lung Diseases, Fungal / therapy* ; Mucorales ; Mucormycosis / diagnosis* ; Mucormycosis / therapy* ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Stem Cell Transplantation / adverse effects ; Substances : Antifungal Agents



Muistiin invasiivisista home- ja sieni infektioista Fokus lähinnä invasiivisessa mukomykoosissa (IM).