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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
Abstract
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.
Supplementary resource (1)
Data
November 2019
... Computerized tomography (CT) scan dapat menunjukkan gambaran sinusitis pada mukormikosis ROS. 20 Modalitas magnetic resonance imaging (MRI) juga dapat digunakan untuk deteksi invasi jamur ke jaringan otak karena dapat memberikan gambaran jaringan otak lebih jelas dibandingkan CT scan. 18 TATA LAKSANA Prinsip tata laksana mukormikosis ROS adalah kombinasi tindakan pembedahan debridemen secepat mungkin, pemberian antijamur, serta mengatasi faktor risiko. ...
... Obat antijamur pilihan utama adalah amphotericin B liposomal dengan dosis 5-10 mg/kgBB/hari. 20 Namun, keterbatasan sediaan di Indonesia membuat amphotericin B deoxycholate lebih sering digunakan sebagai terapi utama. ...
... Alternatif terapi farmakologis lain adalah obat golongan triazole, yaitu isavuconazole dan posaconazole, baik oral maupun intravena. Kedua antijamur tersebut dijadikan sebagai terapi penyelamatan (salvage therapy) apabila pasien mengalami infeksi mukormikosis yang refrakter terhadap amphotericin B. 20 Isavuconazole diberikan dengan dosis 3 x 200 mg/hari pada hari 1-2 dilanjutkan 1 x 200 mg/hari dari hari ketiga hingga seterusnya. Posaconazole diberikan dengan dosis 2 x 300 mg/hari pada hari 1-2 dan dilanjutkan 1 x 300 mg/hari dari hari ketiga hingga seterusnya. ...
Mukormikosis rino-orbito-serebral (ROS) adalah penyakit angioinvasif akibat infeksi jamur Mucorales yang sering ditemukan pada pasien diabetes melitus (DM). Penyakit ini memiliki gambaran khas jaringan nekrotik kehitaman disebut eschar, sehingga disebut juga infeksi “jamur hitam”. Tingkat mortalitas penyakit ini tinggi terutama jika diagnosis dan tata laksana terlambat. Patogenesis mukormikosis ROS pada pasien DM antara lain: interaksi reseptor sel epitel dengan protein jamur, kadar besi bebas dalam darah, dan penurunan imunitas seluler. Diagnosis berdasarkan gambaran klinis dengan faktor risiko, identifikasi jamur, dan pencitraan. Pemeriksaan histopatologis dari jaringan biopsi dapat dikonfirmasi dengan hasil kultur. Tata laksana mukormikosis ROS pada penderita DM meliputi kombinasi debridemen, pemberian antijamur, dan mengatasi kondisi hiperglikemia. Rhino-orbital-cerebral mucormycosis (ROCM) is an angioinvasive disease caused by Mucorales fungal infection; it is common in diabetes mellitus (DM) patients. The disease has a characteristic feature of black necrotic appearance called eschar, thus also called as “black fungus” infection. The mortality rate of this disease is high, especially in delayed diagnosis and treatment. The pathogenesis of ROCM in diabetic patients includes the interaction of epithelial cell receptors with fungal proteins, free iron blood levels, and decreased cellular immunity. Diagnosis is based on clinical features, supporting risk factors, fungus identification, and imaging. Histopathological examination on biopsy tissue confirmed by culture can establish the diagnosis. Management includes a combination of surgical debridement, antifungals, and glycemia control.
... Hence, current recommendations are to combine medical and surgical treatment in the management of mucormycosis and this is backed by evidence from many studies. 29 Of the recommended antifungal agents, only amphotericin B is readily available in Africa, and this is mostly the conventional deoxycholate form. 27 The liposomal type recommended in global guidelines is only patchily available and may not be accessible due to high costs. ...
... 27 The liposomal type recommended in global guidelines is only patchily available and may not be accessible due to high costs. 29 in accuracy by the heterogeneous quality of data which characterised the reports. Some reports had missing data on important variables such as age, sex and even outcome. ...
... A recent survey which assessed the current state of clinical mycology in 40 African institutions showed that liposomal amphotericin B and posaconazole were available in <20% and 5% respectively.29 Our review corroborates these findings as few patients received liposomal Amphotericin B and even fewer had access to posaconazole which was used as salvage therapy in some cases. ...
Mucorales fungi cause mucormycosis, an invasive and rapidly progressive disease which increasingly affects mostly immunocompromised but also immunocompetent individuals. The objective of this study was to highlight the epidemiology, diagnostic modalities, treatment and overall survival of mucormycosis in Africa. We searched for relevant publications in PubMed, Google Scholar and African Journal Online databases covering the period 1960–2022. A total of 147 articles were identified, of which 66 were included in the review, detailing 408 individual cases from 12 African countries; 330 (80.9%) from North Africa, 63 (15.4%) from Southern Africa, seven (1.7%) from East Africa, seven (1.7%) from West Africa and a single case (0.2%) from Central Africa. The most frequently described clinical forms were rhino‐orbital‐cerebral (n=307, 75.2%) and gastrointestinal (n=51, 12.5%). Diabetes mellitus, COVID‐19, malignancies and neutropaenia were the commonest underlying risks in 203 (49.8%), 101 (24.8%), 65 (15.9%) and 53 (13.0%) cases respectively. Most cases, 296 (72.5%) were diagnosed by histopathology. Fungal aetiology was identified in 38 (9.3%), of which the commonest was Rhizopus oryzae/arrhizus (27/38, 71.1%). Of the 408 cases, 334 (81.9%) patients received antifungal therapy, while 244 (59.8%) had surgery. In cases with a specified outcome, survival rate was 59.1% (228/386). Based on case reporting, a substantial burden of mucormycosis occurs in North Africa but the disease is rarely reported in most of the sub‐Saharan region. Establishing a comprehensive registry for standardised data collection could improve understanding of the epidemiology of mucormycosis in the region.
... Critically ill or immunocompromised coronavirus disease 2019 (COVID-19) patients are more liable to suffer from aggressive mycoses [15]. Examples for coexisting conditions that aggravate the aggressiveness of mycoses are the uncontrolled DM, metabolic acidosis and DKA, prolonged neutropenia, increased ferritin levels, hypoxia, prolonged hospitalization with/without mechanical ventilators, trauma, use of corticosteroids, hemopoietic malignancy, immunosuppression associated with a reduced phagocytic activity of white blood cells (WBCs), solid organ transplantation, and allogeneic hematopoietic stem cell transplantation [16][17][18]. ...
... Mucormycosis can virtually affect any organ (e.g., central nervous system [CNS] in general, brain, nose, sinuses, jaw bones, skin, joints, heart, kidneys, lungs, gastrointestinal tract, and invasive mediastinum) [22,23]. Just prior to the emergence of COVID-19 pandemic, the recent global guidelines for the diagnosis and management of mucormycosis in 2019 highlighted that diagnosis of mucormycosis is usually delayed with the rapid disease progression [16,24]. This delayed diagnosis worsens in CAM cases due to many reasons, such as the difficulty in taking invasive tissue biopsies and the unease of aerosol-generating procedures in oral and maxillofacial surgery in COVID-19. ...
... For instance, patients with uncontrolled DM and DKA frequently present with ROCM, whereas those with neutropenia, organ and bone marrow transplant, and hematological malignancies usually exhibit pulmonary involvement. Diagnosis of mucormycosis relies on different integrative factors, such as the availability of imaging techniques (e.g., magnetic resonance imaging and computed tomography), comprehensive mycological and histological assessments, and qualified personnel [16]. Several studies suggested that real-time polymerase chain reaction (RT-PCR), radiological imaging, and culture used for invasive aspergillosis (IA) are also applicable if mucormycosis is suspected [32][33][34][35][36][37]. ...
Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/ without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.
... Mainly, the genera of Absidia, Mucor, Rhizomucor, and Rhizopus are responsible for its aetiology, although Apophysomyces, Cunninghamella, and Saksenaea can also be associated pathogenic species [2,3]. It is an uncommon, rapidly emerging infection of fungi, with high morbidity and mortality that can produce widespread oral-maxillofacial tissue necrosis [4,5]. Due to the rarity of this disease (especially occurred in craniofacial units), it is almost ...
... Both triazoles are strongly recommended salvage treatments. AmB deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings [4]. ...
... Similarly, the historically described 90° branching angle of Mucorales in tissue, versus 45° branching angle of septate moulds, can be difficult to identify in tissue due to interstitial pressures exerted on the fungi by the tissue and alterations in tissue architecture during processing. Thus the wider and irregular (ribbon-like) nature of the hyphae are more reliable distinguishing characteristics than septations and angle of branching [4] antifungal treatment as well as hyperbaric oxygen therapy, along with simultaneous appropriate elimination of underlying causes of immunosuppression and risk factors should be recommended. ...
Purpose
Mucormycosis is a type of fatal infectious disease, rarely involved in the oromaxillofacial region. This study aimed to describe a series of 7 cases with oromaxillofacial mucormycosis and to discuss the epidemiology, clinical features, and treatment algorithm thereof.
Methodology
Seven patients in the author’s affiliation have been treated. They were assessed and presented as per their diagnostic criteria, surgical approach, and mortality rates. Reported cases of mucormycosis originally happened in craniomaxillofacial region were synthesized through a systematic review so as to better discuss its pathogenesis, epidemiology, and management.
Results
Six patients had a primary metabolic disorder, and one immunocompromised patient had a history of aplastic anemia. The criteria for a positive diagnosis of invasive mucormycosis were based on clinical presentation of signs and symptoms, and a biopsy for microbiological culture and histopathologic analysis. Each patient used antifungal drugs and five of them also underwent surgical resection at the same time. Four patients died due to the unregulated spread of mucormycosis, and one patient died owing to her main disease.
Conclusions
Although uncommon in clinical practice setting, mucormycosis should be of great concern in oral and maxillofacial surgery, due to the life-threatening possibility of this disease. The knowledge of early diagnosis and prompt treatment is of utmost importance for saving lives.
... In the case of patients with suspected pulmonary mucormycosis, CT is advised to detect the reversed halo sign (a region of the lungs with ground-glass opacity along with the ring of consolidations) which is a classic hallmark for pulmonary mucormycosis. In addition, CT pulmonary angiograms look for vessel occlusions in the lungs [10,126]. If rhino-orbital-cerebral mucormycosis is suspected, cranial CT or MRI is advised. ...
... In case of its invasion into the eyes or the brain, MRI with high sensitivity is recommended instead of CT. If mucormycosis is confirmed, regular body imaging involving the brain, thorax or abdomen should be done to determine the degree of the infection or dissemination [10]. PET/CT (positron emission tomography/computerized tomography) using [18F]-fluorodeoxyglucose (FDG) can also be employed in the near future for greater sensitivity [127]. ...
... Due to tissue processing, pseudo-septae can be formed or a 45 • angle of branching can be deformed. Hence, the wide and asymmetrical ribbon-shaped hyphal structure is a more consistent feature for microscopic analysis [10]. In acute lesions, hemorrhagic infarcts, coagulative necrosis, angioinvasion, neutrophil infiltration (in non-neutropenic patients), and perineural invasion (PNI) are the distinctive characteristics; while, in chronic lesions, the pyogranulomatous inflammation (PI), and often hyphae enclosed by the Splendore-Hoeppli phenomenon are observed [10]. ...
Patients with respiratory viral infections are more likely to develop co-infections leading to increased fatality. Mucormycosis is an epidemic amidst the COVID-19 pandemic that conveys a ‘double threat’ to the global health fraternity. Mucormycosis is caused by the Mucorales group of fungi and exhibits acute angioinvasion generally in immunocompromised patients. The most familiar foci of infections are sinuses (39%), lungs (24%), and skin tissues (19%) where the overall dissemination occurs in 23% of cases. The mortality rate in the case of disseminated mucormycosis is found to be 96%. Symptoms are mostly nonspecific and often resemble other common bacterial or fungal infections. Currently, COVID-19-associated mucormycosis (CAM) is being reported from a number of countries such as the USA, Turkey, France, Mexico, Iran, Austria, UK, Brazil, and Italy, while India is the hotspot for this deadly co-infection, accounting for approximately 28,252 cases up to June 8, 2021. It strikes patients within 12–18 days after COVID-19 recovery, and nearly 80% require surgery. Nevertheless, the mortality rate can reach 94% if the diagnosis is delayed or remains untreated. Sometimes COVID-19 is the sole predisposing factor for CAM. Therefore, this study may provide a comprehensive resource for clinicians and researchers dealing with fungal infections, intending to link the potential translational knowledge and prospective therapeutic challenges to counter this opportunistic pathogen.
... The epidemiology of mucormycosis has changed over the last few decades. Although it is still considered a rare disease, the incidence of mucormycosis is increasing worldwide, especially in developing countries [1]. This increase is primarily due to the expansion of patient populations most at risk for mucormycosis and the increased use of prophylactic antifungal agents to prevent invasive fungal infections (IFIs) [1,2]. ...
... Although it is still considered a rare disease, the incidence of mucormycosis is increasing worldwide, especially in developing countries [1]. This increase is primarily due to the expansion of patient populations most at risk for mucormycosis and the increased use of prophylactic antifungal agents to prevent invasive fungal infections (IFIs) [1,2]. Patients undergoing hematopoietic stem cell or solid organ transplantation, as well as patients with uncontrolled diabetes mellitus, are at particular risk [3,4]. ...
... Liposomal amphotericin B is the first-line treatment in the management of mucormycosis and is recommended by the European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM), as well as other scientific associations. However, posaconazole and isavuconazole are usually used as salvage treatment in cases of mucormycosis that have poor response to amphotericin B [1,9,10]. ...
Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017–2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC50/90, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC50/90, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC50/90, 0.5/8 mg/L). Voriconazole (MIC50/90, >8/>8 mg/L) and the echinocandins (MIC50/90, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27; MIC50/90, 1/>8 mg/L), Lichtheimia spp. (n = 11; MIC50/90, 4/8 mg/L), and Mucor spp. (n = 8; MIC50, >8 mg/L) isolates, respectively. Posaconazole MIC50/90 values against Rhizopus, Lichtheimia, and Mucor species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively; amphotericin B MIC50/90 values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.
... As far as we know, this is the first report wherein mNGS can detect M. indicus from peripheral blood and liver biopsy tissue, with culture and serological testing yielding negative results (Supplementary Table 1). Moreover, the low sequence reads of M. indicus detected in liver biopsy tissue were caused by formalin-fixed, paraffin-embedded tissue samples we used for sequencing, as formalin damages DNA (Cornely et al., 2019). ...
... Global guidelines for the diagnosis and management of mucormycosis strongly support early and complete surgical treatment of mucormycosis, in addition to systemic antifungal therapy (Cornely et al., 2019). Considering the deteriorating systemic condition and multiple infected lesions in this case, surgical debridement was not possible. ...
... We treated the patient with an empirical combination of LAmB and posaconazole, which is regarded as the most common treatment for mucormycosis. However, the duration of treatment required to treat mucormycosis is not clear (Cornely et al., 2019). In this case, continuous medication adjustments were made based on the patient's condition, medication side effects, and imaging manifestations until substantial radiographical improvement of the liver. ...
Background:
Mucormycosis commonly occurs in immunosuppressed patients with hematological diseases, which can be life-threatening. However, many cases are often misdiagnosed due to lack of specific clinical manifestations. Additionally, the traditional blood culture or serological testing, with a high false-negative rate, is time-consuming. Thus, precise and timely diagnosis of infections is essential for the clinical care of infected patients.
Case presentation:
We report a 29-year-old Chinese man with acute myeloid leukemia (AML) who developed febrile neutropenia after the first course of induction chemotherapy. He received empirical antibiotics, which did not relieve his symptoms. No pathogen was detected by traditional microbiologic assays, while Mucor indicus was identified by metagenomic next-generation sequencing (mNGS) in the blood specimen. Liposomal amphotericin B (LAmB) was used, resulting in the patient's temperature returning to normal. A few days later, abdominal computed tomography (CT) scan showed multiple liver abscesses; fluorescence staining, histopathology, and mNGS identified the causative agent-M. indicus. Posaconazole was combined with LAmB as long-term antifungal treatment. Finally, the patient received allogeneic hematopoietic stem cell transplantation successfully after controlled infection. During follow-up 1 year after transplantation, the number of liver abscesses was reduced to one and remained stable.
Conclusion:
This report described the first case of an AML patient diagnosed with culture-negative disseminated infections caused by M. indicus leading to rare hepatic manifestations using mNGS of peripheral blood and liver biopsy. LAmB combined with posaconazole was given in time, resulting in a favorable outcome. mNGS is a new method that assists in detecting the probable pathogen and increases the accuracy of identifying an etiology.
... Molecular assays target the fungal ribosomal RNA gene (18S rRNA, 5.8S rRNA, 28S rRNA (including D1/D2), and 5S rRNA) as well as the internal transcribed spacers (ITS1 and ITS2,) and the intergenic sequences (IGS1 and IGS2). The use of the ITS region for species identification for Mucorales is widely accepted and supported by CLSI guidelines for resolution to genus and even species level [21,22]. However, it lacks discrimination of closely related species (sibling species). ...
... Given the uncommon nature of infection and no direct evidence for prophylaxis directed solely towards mucormycosis, primary antifungal prophylaxis for mucormycosis is not recommended. In usual clinical setting prophylaxis is directed against a broad range of fungal infections, including candidiasis and aspergillosis [21]. As mentioned before, standard antifungal prophylaxis against over molds may even lead to breakthrough of resistant mucormycosis. ...
... As mentioned before, standard antifungal prophylaxis against over molds may even lead to breakthrough of resistant mucormycosis. However, breakthrough mucormycosis has been a rare event during prophylaxis with posaconazole oral suspension, and exposure due to posaconazole delayed release tablets, or intravenous infusions may result in even lower invasive fungal infection rates [18,21]. Isavuconazole is marginally supported in neutropenic patients and there is a lack of evidence to support liposomal AmB prophylaxis for patients receiving immunosuppressive treatment [24]. ...
... Black fungal infection cases during COVID-19 pandemic 3 rd wave were showed in India, Bangladesh and other countries [13]. Inhalation of Mucor spores , contaminated wound or ingestion of food contaminated by spores can cause the infection among the risk group of patients [3][4][5][6][7][8][9][10][11][12][13][14]18]. ...
... [15] reported that female medical care worker scored more in participating and have adequate knowledge comparing to male which also showed in the present study.In agreement with the present study [11,8] reported that medicine students and doctors were found more aware and better knowledge of black fungal infection comparing with other medical health care providers. In according to results in the present study, Globally mucormycosis infection around the world usually found more in tropical, warm and humid countries and the etiological agents mostly Rhizopusspp and Mucorspp as mentioned by [17],the most common form is rhinocerebralmucormycosis also associated with eyes and face lesions [12],several studies reported the relationship between COVID-19 and mucourmycosis which is probably due to the weak immune response as a result of decrease in T lymphocytes CD4+ and CD8+ [1][2][3][4][5][6][7]10] and other factors that increasing the risk as diabetes mellitus reported by [2,9 ] proven that administration of corticosteroids with COVID -19 patients on mechanical ventilation could lead to increase the risk of mucormycosis. For treatment of mucormycosis as mentioned by [4,17] antifungal drugs with surgical removal of necrotic tissue and surroundinghealthy tissue can lead to control and prevent the spreading of mucormycosisinfection. ...
... In according to results in the present study, Globally mucormycosis infection around the world usually found more in tropical, warm and humid countries and the etiological agents mostly Rhizopusspp and Mucorspp as mentioned by [17],the most common form is rhinocerebralmucormycosis also associated with eyes and face lesions [12],several studies reported the relationship between COVID-19 and mucourmycosis which is probably due to the weak immune response as a result of decrease in T lymphocytes CD4+ and CD8+ [1][2][3][4][5][6][7]10] and other factors that increasing the risk as diabetes mellitus reported by [2,9 ] proven that administration of corticosteroids with COVID -19 patients on mechanical ventilation could lead to increase the risk of mucormycosis. For treatment of mucormycosis as mentioned by [4,17] antifungal drugs with surgical removal of necrotic tissue and surroundinghealthy tissue can lead to control and prevent the spreading of mucormycosisinfection. The present study showed that the medical health care participants were not fully aware of mucormycosis causative agent, factors helping infection, methods of treatment and managements. ...
Objectives: to observe and analyze data about the awareness of Mucormycosis (black fungi) infection associated with some cases of COVID-19 after recovery and factors related to it, targeting population Medical health care students in Hail university and Imam Abdulrahman Bin Faisal University, Kingdom of Saudi Arabia. Methods: surveillance cross sectional study, data were collected from 15th of October 2021 till 28th of February 2022. Study population Male and Females / adults / Medical health care students in Hail university and Imam Abdulrahman Bin Faisal University, Kingdom of Saudi Arabia, using questionnaires, statistical analysis was done by SPSS 22. Results: 216 responses to the questioner. The study finding showed that(62%) from Hail university and (38%) were from Imam Abdulrahman Bin Faisal University. As for gender (66.7%) were female and (33.3%) were males ,also results showed that from Medicine college (59.7%) ,(18.5%) from Applied medical college,(7.9%) pharmacy ,(6%) students from public health college,(4.2%) nursing and (3.7%) from Dentistry college. Regarding COVID-19 status and vaccination (90.3%) were vaccinated by 2 doses and (74.1%) were not infected by COVID-19 . About the awareness about Mucormycosisand knowing about the type of infection ,causative agent and contagiousness (63%) not knowing the type of infection ,(43.5%) thinking its a contagious disease while (74.1%) consider it as fungal disease .(45.4%) answered its a mucor mold type of fungi and (39.8%) answered its belong to genus mucor . About factors that can play a role in infection asage , gender , race , environment and lifestyle (78.7%) agreed that these factors play an important role in infection ,(37.5%) explained that giving name black fungi infection is due to the color of the lesion while (26.9%) giving the reason that due to color of the fungi or because it can lead to death .About lesions and which part of the body do you think mostly affected results showed Rhinocerebral (46.3%), followed by (25.5%) in the eyes ,(15.3%) in the ears and(13%) in the brain .(48.1%) agreed that patients with COVID-19 infection could be more susceptible to mucormycosis infection . (59.3%) given the reason that having history of weak immunity with COVID-19 infection can lead to mucormycosis secondary infection while (23.1%) believe that protocol of treatment used in COVID-19 infection may be the cause and (10.1%) think that patients with COVID-19 associated with history of diabetes mellitus lead to black fungi infection. (56%) of the results showed that participants think that vaccination can prevent black fungi infection ,(42.1%) agreed that black fungi can be treatable by antifungal drugs with surgical interference,(36.6%) answered that it can be treat by antifungal drugs only ,( 12.5%) think that it can be treated with antibiotics and (8.8%) considered that black fungi not treatable .(79.2%) believed that mucormycosis infection can lead to death. Conclusion: awareness is the golden key to manage any emerging public health problem specially among health care provider in all specialties, Spreading the knowledge and updates among society of Medical health care students about mucormycosis causative agent, factors lead to infection specially during the COVID-19 pandemic ,suggested treatment and management of such case can help in controlling , preventions . know how to deal with Post COVID-19 situation and prepare for it.
... Mucormycosis. Lipid formulations of AMB are considered the mainstay treatment of mucormycosis, based on uncontrolled case series and substantial clinical experience [133]. Randomized controlled trials have not been conducted, and the prospects for such trials in the future are limited by the rarity and lethality of this infection, as well as the need to account for multiple confounding underlying conditions and interventions. ...
... Doubling of serum creatinine occurred in 40% of patients. Taken together, observational data support the use of LAMB or ABLC at a minimal dose of 5 mg/kg/day for the treatment of mucormycosis [133]. Studies in diabetic mice have shown that a LAMB dose of 7.5 mg/kg/day and an ABLC dose of 15 mg/kg/day are required to treat CNS mucormycosis [137]. ...
... Studies in diabetic mice have shown that a LAMB dose of 7.5 mg/kg/day and an ABLC dose of 15 mg/kg/day are required to treat CNS mucormycosis [137]. The European Confederation of Medical, Mycology (ECMM) clinical guidelines recommend LAMB at a dose of 10 mg/kg/day if the CNS is involved [133]. ...
Antifungal therapy for pulmonary fungal diseases is in a state of flux. Amphotericin B, the time-honored standard of care for many years, has been replaced by agents demonstrating superior efficacy and safety, including extended-spectrum triazoles and liposomal amphotericin B. Voriconazole, which became the treatment of choice for most pulmonary mold diseases, has been compared with posaconazole and itraconazole, both of which have shown clinical efficacy similar to that of voriconazole, with fewer adverse events. With the worldwide expansion of azole-resistant Aspergillus fumigatus and infections with intrinsically resistant non-Aspergillus molds, the need for newer antifungals with novel mechanisms of action becomes ever more pressing.
... The current mainstays of treatment for mucormycosis include amphotericin B, posaconazole, and isavuconazole, in combination with surgical debridement. However, these newer antifungal agents, such as posaconazole and isavuconazole, are expensive and not always readily available [9]. While itraconazole has not been commonly used for the treatment of mucormycosis, its MIC for certain species, such as Rhizopus arrhizus, has been reported to be low. ...
... Therefore, accurate identification of the species causing the infection is critical to ensuring appropriate management and selecting the most effective antifungal agent. Additionally, timely administration of antifungal therapy is crucial for improving clinical outcomes in invasive fungal infections [9,11]. ...
Mucormycosis is a serious and often fatal fungal infection that is most commonly observed in immunocompromised individuals. The mortality rate of mucormycosis is high if left untreated, and successful treatment requires a combination of antifungal therapy, surgical intervention, and reversal of the underlying immunocompromised state. The choice of antifungal treatment is crucial and depends on several factors, including the safety profile of the drug, its spectrum of activity, and the species of fungus causing the infection. In this report, we describe a case of a patient who presented with mucormycosis and was successfully treated with a combination of antifungal therapy, surgical excision of affected tissue, and reversal of the underlying immunocompromised state. Our report underscores the importance of early recognition and aggressive treatment of mucormycosis to improve outcomes for affected patients.
... Mucormycosis is a severe and lethal fungal disease. Urgent surgical intervention and antifungal therapy are lifesaving 1 . The causal pathogens are fungi from the mucorales order with the main reported genera Rhizopus spp, Mucor spp, and Rhizomucor spp 1 . ...
... Clinically, infection is classified based on anatomic localization, such as cutaneous, disseminated, gastrointestinal, pulmonary, and rhinocerebral 2 . Classical risk factors associated with mucormycosis include uncontrolled diabetes mellitus, direct inoculation, corticotherapy, immunosuppression, solid organ transplantation, onco-hematological disease, and immunotherapy (especially with tocilizumab) used in the management of severe coronavirus disease 2019 (COVID-19) 1,3 . In the last 2 years, there has been a notable incidence of COVID-19-associated mucormycosis (CAM). ...
Background:
Mucormycosis is a severe invasive fungal disease. During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks have been reported worldwide, but epidemiological studies are still scarce in Brazil.
Methods:
We conducted a time-series cohort hospitalization study (2010-2021) in southeastern Brazil.
Results:
There were 311 cases (85 during the pandemic), with significant (P < 0.05) involvement of patients older than 40 years (84%), white patients (78%), rhinocerebral site (63%), and São Paulo State residents (84%).
Conclusions:
Mucormycosis hospitalizations were highly prevalent. Further studies are needed to assess the burden of COVID-19 on mucormycosis in Brazil.
... 6 These areas include south, central, southeastern and midwestern United States, Canadian provinces bordering the Great Lakes, and areas along the St. Lawrence River. 15,27,28 It is reported to be endemic to Africa and related to B percursus and B emzantsi. 15,28 Pathogenesis Blastomyces dermatitidis can be found in decaying organic matter such as in soil, leaf litter, and wood. ...
... 15,27,28 It is reported to be endemic to Africa and related to B percursus and B emzantsi. 15,28 Pathogenesis Blastomyces dermatitidis can be found in decaying organic matter such as in soil, leaf litter, and wood. 14,15 Interaction with such soil or recreational activities leads to aerosolized conidia of B dermatitidis being inhaled. ...
Oral fungal infections are opportunistic and due to impaired host resistance. The increasing number of immunosuppressed individuals contributes to rising numbers of mycoses worldwide, and the ease of global migration has allowed the geographic range of endemic mycoses to expand. Deep fungal infections can clinically mimic other pathologic conditions including malignancy. This review highlights the pathogenesis, clinical features, diagnosis, and treatment recommendations of eight fungal infections that can be encountered in the dental setting.
... Invasive mucormycosis (IM) is a rapidly-progressive, angioinvasive fungal infection (IFI) with very high mortality. In hematology patients, IM has been classically associated with acute myeloid leukemia and allogeneic stem cell transplantation and its complications, particularly Graftversus-Host-Disease (GvHD), prolonged neutropenia, highdose corticosteroids, iron overload, fludarabine exposure, and Aspergillus-directed prophylaxis such as voriconazole [1][2][3][4][5]. Broader risk is also conferred by diabetes and older age [2]. ...
... Current guidelines do not recommend the routine use of anti-mold prophylaxis in autoSCT recipients [1,16], although one study suggested that, due to cumulative risk, prophylaxis may be justified in lymphoma patients aged over 60 years, who are undergoing autoSCT after ≥ 3 lines of chemotherapy [8]. Our patient would not have qualified using these criteria. ...
Invasive fungal infections (IFI) are challenging to predict, diagnose and treat, and are associated with a particularly high mortality among patients with hematological malignancies. They are relatively uncommon in patients with lymphoma, compared with those with acute leukemia or undergoing allogeneic transplantation. We present a patient, autografted for recurrent lymphoma, with fever and refractory diarrhea persisting post engraftment, eventually attributable to disseminated mucor infection. This case illustrates the challenge of timely diagnosis and initiation of treatment for IFI in lymphoma patients, who do not routinely receive antifungal prophylaxis, and the importance of aggressive investigation and symptom-directed tissue sampling for evidence of IFI in febrile immunocompromised hosts not responding to broad-spectrum antibiotics.
... The patient may present unilateral facial swelling, proptosis and palatal and/or eyelid fistulas, and necrosis. Cases of gastrointestinal and kidney infections have already been reported in the literature, but they are rare manifestations [95][96][97]. ...
... Mucormycosis treatment can be performed by reversing a predisposing factor (if possible), administration of antifungal drugs or, in more advanced cases, it requires the complete removal of infected tissue by surgical procedure [97]. Early fungal diagnosis is extremely important in order to initiate proper treatment and avoid the need for surgery. ...
Since the World Health Organization (WHO) declared the pandemic of coronavirus disease-2019 (COVID-19) on March 11th, 2020, the world has faced a health crisis that includes challenges such as its diagnosis, treatment and prevention, resulting in more than 485 million confirmed cases worldwide and more than 6 million deaths (March 31th, 2022). The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to the suppression of the immune system, particularly due to the storm of inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-6, IL-2 and IL-1) and the reduction of anti-inflammatory cells (e.g., CD4+ and CD8+ T lymphocytes). These factors, when associated with the use of steroids, prolonged stay in the intensive care unit (ICU), older age, diabetes, cardiovascular and pulmonary diseases as well as inherited and acquired immunodeficiency, contribute to the colonization of other infectious agents, such as respiratory viruses, gram-positive and gram-negative bacteria, yeasts and filamentous fungi. The incidence of opportunistic fungal infections has increased significantly in patients with COVID-19, especially in individuals with critical medical conditions and presenting comorbidities, such as the ones cited above. The main fungal agents causing coinfections in these particular patients are Aspergillus spp., Candida spp. and fungi belonging to the order Mucorales. The similarity of clinical symptoms between COVID-19 and fungal infections, such as fever, dry cough, dyspnea, myalgia and headache, makes it harder to get a conclusive laboratory identification and diagnosis, which represents a challenge for treatment. To worsen this bad scenario, the available antifungals are substantially limited and some fungal species are intrinsically resistant to classical chemotherapeutic drugs used in the clinical settings. In parallel, the antifungals can also present drug interactions besides serious and severe side effects, such as hepatotoxicity and nephrotoxicity, which can greatly aggravate the patients' clinical condition. All these facts highlight the urgent need for early diagnosis of the fungal pathogens for the proper choice of antifungal treatment in order to combat these relevant yet still neglected diseases on a global scale. The present chapter focused on summarizing the main fungal infections reported in COVID-19-positive patients.
... [3] Posaconazole and isavuconazole have also shown efficacy similar to amphotericin B and endorsed for first-line management of mucormycosis. [57] Due to widespread craniofacial disease involvement, a multidisciplinary approach must be followed during surgery as well as postsurgical rehabilitation of patients with ROCM. Aggressive debridement of necrotic tissues must be done to remove disease-ridden and nonviable tissue. ...
... Cultureindependent diagnostic procedures are now possible thanks to recent developments in molecular biology techniques. The most popular diagnostic tools are nucleic acid probes and immunological detection and identification using unique metabolites [2][3][4][5]. ...
A considerable number of fungal strains have developed resistant to various available antifungal agents due to CPY, FKS and or ERG11 genes complicating coinfection cases of SAR COV-2 virus. Therefore, this study sought to isolate, identify azole and polyene resistant genes in fungal pathogens isolated from confirmed SARS-CoV-2 individual in Oyo State, Nigeria. Nasopharyngeal samples were collected from symptomatic and asymptomatic SARS-CoV-2 infected adult from September, 2020 to April, 2021. Samples were cultured on Sabouraud Dextrose Agar at room and at 37 oC temperature for 7days. Identification of the fungal isolates were performed using MALDITOF MS VITEK. Antifungal Susceptibility Testing (AFST) were performed using Kirby bauer disc diffusion method. The resistant genes in fugal isolates were determined by Polymerase Chain Reaction with specific primers and resistant genes were amplified using agarose gel electrophoresis. Out of 63(15.8%) fungal isolates recorded from 400 samples collected, Asipergillus flavus 11(17.5%), Aspergillus niger 9(14.3%), Candida albicans 7(11.1%), Candida guillermondii 2(3.2%), Candida parapsilosis 2(3.2%), Candida famata 2(3.2%), Candida tropicalis 5(7.9%) and Lodderomyces elongisporus 25(39%) having highest frequency were recorded respectively. Nystatin (84.1%) had highest susceptibility testing and Ketoconazole (39.7%) had the least phenotypically. 10 (52.6%) isolates possessed CPY gene, 8(42.1%) isolates carried FKS gene, 9(47.4%) isolates had ERG11 gene molecularly.
... Advances in chemotherapy, organ transplantation, and therapeutic application of immunosuppressants and biologicals have led to an increased number of immunosuppressed patients with a concomitant increase in the clinical relevance of associated invasive mycoses [1][2][3] . However, the etiology and clinical features of deep mycosis are still not well established, partly because of the lower sensitivity of culture tests for detecting invasive mycosis in real-world practical settings. ...
Background: β-D-glucan detection is a useful diagnostic indicator of invasive mycosis. However, the differences among the commercial β-D-glucan assays are unclear. Herein, we explored the diagnostic value of various β-D-glucan assay reagents.
Methods: This prospective observational study involved 175 eligible patients suspected to have fungal infections. For all participants, culture examinations were conducted with specimens obtained from the infected site (or blood culture), and β-D-glucan was measured using three commercial kits: Wako β-glucan test (Wako), Fungitech G-test MKII “Nissui” (MKII), and Fungitech G-test ES “Nissui” (ES).
Results: A total of 163 participants were included. Among them, 32 cases of invasive mycosis, 34 cases with mycotic colonization infection, and 97 cases with non-fungal infections were confirmed. Regarding the diagnostic value of the commercial kits for invasive mycosis, the areas under the receiver operating characteristic curves were > 0.8 for all the agents. However, on the basis of the cut-off value set by the manufacturer, the sensitivity and specificity of the three kits for definitive invasive infection were 80.0% and 90.6% with Wako, 80.0% and 80.7% with MKII, and 86.7% and 71.8% with ES, respectively. Moreover, the rate of false-positive β-D-glucan elevation detection in patients with negative fungal culture was 9.3% with Wako, 18.6% with MKII, and 23.7% with ES.
Conclusion: Despite the high diagnostic value of β-D-glucan detection in invasive fungal infections, caution should be exercised in interpreting the value of the assay reagents.
... In salvage treatment for Mucormycosis both the azoles are used. [9] Adjunct therapies should be considered in the management of Mucormycosis. Use of hyperbaric oxygen kills the fungus by providing oxygen to neutrophils. ...
... However, Posaconazole has poor CNS penetration (23). One of the strategies is to use a higher dosage (10 mg/Kg) of amphotericin-B in invasive intracranial mucormycosis by intravenous route of administration (24). Anecdotal reports suggest adjuvant use of intraocular topical instillation of amphotericin in sino-orbital mucormycosis to achieve disease-free status in a post-surgical group after exenteration of orbit (25,26). ...
... Mucormycosis treatment includes surgical procedures and the treatment of predisposing factors combined with systemic antifungal therapy with liposomal formulation of amphotericin B, since this drug exhibits good activity against several Mucorales species [7]. Azoles such as itraconazole, fluconazole and voriconazole usually have no effect against most mucormycosis-causing pathogens. ...
Mucormycosis is considered concerning invasive fungal infections due to its high mortality rates, difficult diagnosis and limited treatment approaches. Mucorales species are highly resistant to many antifungal agents and the search for alternatives is an urgent need. In the present study, a library with 400 compounds called the Pandemic Response Box® was used and four compounds were identified: alexidine and three non-commercial molecules. These compounds showed anti-biofilm activity, as well as alterations in fungal morphology and cell wall and plasma membrane structure. They also induced oxidative stress and mitochondrial membrane depolarization. In silico analysis revealed promising pharmacological parameters. These results suggest that these four compounds are potent candidates to be considered in future studies for the development of new approaches to treat mucormycosis.
... According to the pathogenic proportions of mucormycosis, we assembled, annotated and analyzed the genomes of (i) 25 (Table S2). ...
Mucoralean fungi offer various pathogens to cause mucormycosis, especially in immunodeficient patients. Over the past decades, both the morbidity and mortality of mucormycosis have increased rapidly, particularly in developing countries. Nowadays, mucormycosis more often happens in India for the COVID-19 pandemic and its backward diagnostic techniques. Our epidemiologic outcomes show several identifications of Mucoralean fungi are limited to genus, while Rhizopus species, Mucor species and Lichtheimia species have high proportions. To find more molecular targets to make rapid and accurate identifications of Mucorales genus and species, Pan-genome analysis and Phylogenetic tree are conducted with four Mucorales isolates we sequenced and 43 fungi from NCBI. A few Mucorales- specific genes have been found such as STE/STE20 protein kinase, GH36 and sel1 repeat protein. Mucorales genus-specific genes are also found in Lichtheimia species and Cunninghamella species, which covered cellular structure, biochemistry metabolism, molecular processing, and signal transduction. Reported proteins related to the virulence of Mucorales species were run with Orthofinder and 112092 , cotH3 , gcn4 and igp1 have shown the potential to be the direct identification as well as the virulence detection of Mucorales species. The molecular biological techniques need to be promoted, for which our study provide hypothesis and feasibility analysis.
... The antifungal treatment includes amphotericin B lipid complex, liposomal amphotericin B and posaconazole as first line drugs in combination with isavuconazole. Posaconazole can be given as prophylaxis to those with high-risk factor and in graft versus-host disease (46). ...
Invasive fungal diseases (IFDs) are major causes of morbidity and mortality among hospitalized patients all over the world with a global prevalence of 15%. Since the first case of COVID-19 was reported on February 27, 2020, in Nigeria, it had been discovered across all geopolitical zones in Nigeria. As the medical community confronts the ongoing COVID-19 pandemic, determining whether patients infected with SARS-CoV-2 develop fungal complications, especially invasive aspergillosis, is crucial. This review aimed to highlight the fungal co-infections that might be associated with SARS-CoV-2 infection, and modalities for their diagnosis, prevention, and management, with the view to reducing the high mortality associated with these infections.
... Thus, this infection's manifestations vary, ranging from local pain, headache, proptosis, ophthalmoplegia, and other neurological manifestations (16). In rhinocerebral mucormycosis, the disease's hallmark is attributed to tissue necrosis from angioinvasion and subsequent thrombosis (17). In patients suspected of having rhinocerebral mucormycosis, a comprehensive assessment of the patient's medical history and physical and neurological examination followed by imaging of the affected zones can crucially lead to con rming the diagnosis. ...
Introduction
In patients suffering from COVID-19, immunocompromised conditions or immunosuppressive medications such as corticosteroids may predispose them to early or delayed invasive fungal infections that invade cerebral components. This study, for the first time, describes a case of COVID-19 disease diagnosed with rhinocerebral mucormycosis through cerebrospinal fluid (CSF) analysis.
Case presentation
A 32-year-old woman with a history of referral and hospitalization due to COVID-19 about a month ago was being treated with immunosuppressive drugs, manifested by lower extremity plegia. In the imaging assessment, intracranial hemorrhage (thalamus zone) and mass like lesion were revealed. In cytological assessment, acute inflammations associated with fungal infection in accordance with the diagnosis of mucormycosis were definitively confirmed. Despite antifungal medication, consciousness declined one week later, and the patient developed thromboembolism and died.
Conclusion
In patients with a COVID-19 background of immunosuppressive therapy or clinical situations related to immunosuppression such as uncontrolled diabetes, rhinocerebral mucormycosis will always be an ambush. Therefore, screening and prevention measures should be considered.
... Rarer to find this entity in immunocompetent patients without any risk factors. 1,2 Specific guidelines for the treatment are not yet known but combined medical and surgical therapy is considered the best modality for its management. After the second wave of COVID-19 infection in India, the country faced an epidemic of mucormycosis in previously COVID-positive patients. ...
... Intravenous lipid formulation of amphotericin B was the drug of choice for initial therapy. Posaconazole and isavuconazole were also used as step down therapy after adequate response was achieved [11]. Some post-therapeutic biopsy samples were also received after 5 -7 days of antifungal therapy. ...
Background:
Mucormycosis necessitates rapid diagnosis and treatment. Microscopy and culture have been considered the gold standard for diagnosis but both take time of 3 - 5 days. KOH mount is another method for fungal identification that takes 1 - 2 h, but it has its own limitations. This study evaluated crush smear as a means of rapid cytological diagnosis.
Methods:
Biopsy tissue (pre-treatment) from clinically suspicious mucormycosis patients (n = 52) was received in normal saline and crush/imprint smears were prepared; the remaining tissue was processed as routine biopsy specimen. After the rapid initial cytological identification, the patients were managed according to the standard clinical protocol. Random post-therapeutic biopsy samples of some of these patients (n = 19) were also obtained and again evaluated cytologically.
Results:
Crush smears showed sensitivity/specificity of 77.7%/75.0% with histopathology and 72.2%/62.5% with culture, respectively, while KOH mount had values of 71.4%/70.5% with histopathology and 79.3%/69.5% with culture, respectively. Degenerative fungal morphological characteristics and cellular inflammatory infiltrate (predominantly neutrophilic) in the vicinity of fungal hyphae were compared in pre- and post-treatment groups, and we found a statistically significant difference (P < 0.05) between them.
Conclusion:
Our preliminary results suggest that crush smear cytology is a simple, rapid, cost-effective and easily available method for diagnosing mucormycosis. Moreover, crush smears also demonstrated morphological alteration in hyphal structure and accompanying immune cell infiltration which may provide valuable insights into mechanism of therapy/host immune response against fungal pathogen.
... The diagnosis of mucormycosis was based on global guidelines published by the European federation of medical mycology. 9 Patients presenting to the ENT OPD underwent clinical examination and diagnostic nasal endoscopy. The black discoloration of turbinates was a pathognomonic sign of mucormycosis. ...
Background: The second wave of the COVID-19 pandemic in India was associated with an increased incidence of rhino-orbital-cerebral mucormycosis. The objective of this paper was to prospectively explore the epidemiology, management, and results of 18 months follow-up of patients presenting with COVID associated mucormycosis at a tertiary referral centre in India. Methods: Patients presenting with symptoms suggestive of COVID-associated mucormycosis over two months were included in the study. Patients were staged based on the extent of the disease. Surgery was the primary modality of treatment except in those with intracranial spread, altered sensorium, and poor prognosis. A combination of liposomal amphotericin B and posaconazole was used as adjunct medical treatment. Patients were followed up and outcomes at one year of treatment were recorded. Results: Out of a total of 26 patients who were diagnosed with COVID associated mucormycosis, 21 patients underwent bimodality treatment (medical and surgical). The extent of surgery was based on the stage of the disease. Six eyes received retrobulbar injections of Amphotericin B to salvage vision. The overall mortality was 38.46% and 23.8% in those where the intent of treatment was curative. At the end of one year, 16 of 21 operated patients survived with mild to severe sequelae. Conclusions: Mucormycosis is a deadly fungal infection with high mortality. Early diagnosis and prompt, aggressive treatment is paramount in preventing mortality. A multidisciplinary approach is useful for effective management. Continuous follow up is paramount to identifying and treating complications.
... The treatment recommendations can be supported by the global guideline for the diagnosis and management of mucormycosis in 2019 by the European Confederation of Medical Mycology which supports an early debridement in addition to systemic antifungal treatment. [3] Hence, we face a string of problems and constellation of challenges which can happen while providing general anesthesia to the patients. ...
The sudden epidemic of mucormycosis amid COVID-19 pandemic has significantly challenged our understanding of the disease while affecting the whole medical and surgical management. Overzealous use of steroids in the management of covid-19 and uncontrolled diabetes mellitus has resulted in a tremendous rise in mucormycosis cases further burdening the already strained health care infrastructure and health care workers, especially the anesthesiologists. While working in a tertiary care institute of the country, we have been facing multiple challenges in its anesthetic management on a daily basis. This article is a case series involving four different patients who were operated for rhino-orbito-cerebral mucormycosis with a brief discussion on various aspects of this multisystem epidemic.
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 (CAM), through a systematic review and meta-analysis.
Data sources:
PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.
Study eligibility criteria:
Studies reporting individual-level information in adult CAM patients between January 1, 2020 and December 28, 2022.
Participants:
Adults who developed mucormycosis during or after COVID-19.
Assessment of risk of bias:
Quality assessment was performed based on the National Institutes of Health Quality Assessment Tool for Case Series Studies.
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.
Results:
958 individual cases reported from forty-five countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries (LMIC). 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 co-infection (p=0.037), and tocilizumab use during COVID-19 (p=0.018) increased the mortality. CAM occurred on average 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus co-infection and pulmonary mucormycosis was made on average 15.4 days (range 0-35) and 14.0 days (range 0-53) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of cases. The overall mortality rate was 38.9% (303/780).
Conclusion:
Mortality of CAM was high, and most reports were from LMIC countries. We detected novel risk factors for CAM such as older age, specific comorbidities, Aspergillus co-infection and tocilizumab use, in addition to previously identified factors.
There is a lack of research evaluating the role of references in hospital policies. The goal of this study was to describe the type of literature used as a reference in medication policies and evaluate the agreement of the policy with evidence-based guidelines. One hundred forty-seven pharmacy owned policies met inclusion criteria; 27.2% of the policies contained references, in which tertiary literature was the most frequently cited source (90%), followed by primary (47.5%), and lastly secondary (27.5%). When references were used, all policies agreed with current guidelines. For policies without references, 3.7% disagreed with published guidelines. Disagreement with guidelines may negatively impact patient care, therefore health systems should incorporate librarians into clinical policy development and review to ensure the best available evidence is incorporated into polices.
Mucormycosis is a rare but life-threatening fungal infection due to molds of the order Mucorales. The incidence has been increasing over recent decades. Worldwide, pulmonary mucormycosis (PM) presents in the lungs, which are the third main location for the infection after the rhino-orbito-cerebral (ROC) areas and the skin. The main risk factors for PM include hematological malignancies and solid organ transplantation, whereas ROC infections classically are classically favored by diabetes mellitus. The differences between the ROC and pulmonary locations are possibly explained by the activation of different mammalian receptors—GRP78 in nasal epithelial cells and integrin β1 in alveolar epithelial cells—in response to Mucorales. Alveolar macrophages and neutrophils play a key role in the host defense against Mucorales. The diagnosis of PM relies on CT scans, cultures, PCR tests, and histology. The reversed halo sign is an early, but very suggestive, sign of PM in neutropenic patients. Recently, the serum PCR test showed a very encouraging performance for the diagnosis and follow-up of mucormycosis. Liposomal amphotericin B is the drug of choice for first-line therapy, together with correction of underlying disease and surgery when feasible. After a stable or partial response, the step-down treatment includes oral isavuconazole or posaconazole delayed release tablets until a complete response is achieved. Secondary prophylaxis should be discussed when there is any risk of relapse, such as the persistence of neutropenia or the prolonged use of high-dose immunosuppressive therapy. Despite these novelties, the mortality rate from PM remains higher than 50%. Therefore, future research must define the place for combination therapy and adjunctive treatments, while the development of new treatments is necessary.
Granulomatosis with polyangiitis (GPA) is a primary vasculitis associated with antineutrophil cytoplasmic antibodies, characterized by necrotizing vasculitis with predominant involvement of small vessels of various localizations and necrotizing granulomatous inflammation with multiple clinical manifestations. GPA remains one of the most severe systemic vasculitis with unfavorable prognosis. When analyzing the course of the disease, there are two variants of GPA, local (with lesions of the upper respiratory tract, URT, organs of vision and hearing) and generalized (with lesions of the URT, organs of vision and hearing in combination with the lungs and/or kidneys, gastrointestinal tract, nervous systems, skin involvement).The article discusses the differential diagnosis of the disease with the nasal cavity and paranasal sinuses lesions onset, which requires an interdisciplinary approach and interaction of doctors of different specialties.
After the declaration of coronavirus as a pandemic in 2019, a strong relationship has been shown between the sudden upsurge of mucormycosis occurrence in patients with history of COVID-19. This relation can be explained by the effect of coronavirus on the patient's immune system, the infection worsens the effect of the underlying predisposing factors such as diabetes mellitus and drugs therapies that were used in the treatment of COVID-19, especially corticosteroids. Mucormycosis presented mainly in patients who had comorbid conditions like diabetes, steroid therapy, or chemotherapy. This study showed the association between the increase in the prevalence of mucormycosis in patients with COVID-19 and proved that diabetes was the main risk factor for this fungal infection. The study confirmed that many factors determined the prognosis in the management of mucormycosis, first of them is the early diagnosis which depends on a high index of clinical suspicion, accurate procedures for diagnosis confirmation such as biopsy, fungal culture media, radiological examination by computed tomography scan or magnetic resonance imaging, Evaluation of prognostic factors e154
The specialty of otolaryngology and head and neck surgery involves various subspecialties, encompassing clinical conditions ranging from medical to surgical issues in infections, noninfectious benign conditions and various benign and malignant tumors. Drug repurposing has proven to be significant in multiple fields and is still investigational in many promising possible solutions to different clinical challenges in this specialty. We discuss some classes of drugs that have been successfully repurposed for ENT pathologies. We also discuss the novel research goals that are being pursued in our department in the context of drug repurposing for airway infectious diseases including COVID-10 and mucormycosis. There has been a silent and underappreciated rise in drug-resistant invasive fungal infections (IFIs). Emerging Mucorales are difficult to diagnose and tolerant to many of the frontline antifungal therapies. There is an urgent need to combat these emerging pathogens and investigate the molecular mechanisms underlying their potentiated virulence traits to identify potential therapeutic targets susceptible to anti-fungal compounds. The drug development process for IFIs remains largely expensive, and is inherently risky. These challenges declare an urgent need for discovery of new antifungal drugs and encourage drug repurposing as alternative approach to fungal control. The understanding of molecular underpinnings behind fungi and human host continue to grow, however, further research endeavors are underway to fully explore the fungal pathogenesis, (including the role of iron) to gather new insights to achieve improved therapeutics. Above all, creative screening tools and out-of-the-box ideas aimed at increasing the possibility of identifying potential first-in-class antifungals are highly encouraged. The recently emerging fungal co-infections in the COVID-19 disease patients has revived the interest in the pathophysiology and clinical management of the IFIs, and identification of potential druggable nodes in olfactory niche to inhibit the spread of COVID-19 and associated co-infections by leveraging in vitro-disease models of host-pathogen interaction. We employed our recently established COVID-19 disease model to decipher potential anti-metabolic molecules that can be repurposed as novel bilateral drugs having anti-fungal and host-directed features with extended applicability in diabetes, COVID-19, and mucormycosis with and without COVID-19.
Chromatin modifications play a fundamental role in controlling transcription and genome stability and yet despite their importance, are poorly understood in early-diverging fungi. We present a comprehensive study of histone lysine and DNA methyltransferases across the Mucoromycota, emphasizing heterochromatin formation pathways that rely on the Clr4 complex involved in H3K9-methylation, the Polycomb-repressive complex 2 driving H3K27-methylation, or DNMT1-like methyltransferases that catalyze 5mC DNA methylation. Our analysis uncovered H3K9-methylated heterochromatin as the major chromatin modification repressing transcription in these fungi, which lack both Polycomb silencing and cytosine methylation. Although small RNAs generated by RNA interference (RNAi) pathways facilitate the formation of heterochromatin in many eukaryotic organisms, we show that RNAi is not required to maintain either genomic or centromeric heterochromatin in Mucor. H3K9-methylation and RNAi act independently to control centromeric regions, suggesting a functional subspecialization. Whereas the H3K9 methyltransferase Clr4 and heterochromatin formation are essential for cell viability, RNAi is dispensable for viability yet acts as the main epigenetic, regulatory force repressing transposition of centromeric GremLINE1 elements. Mutations inactivating canonical RNAi lead to rampant transposition and insertional inactivation of targets resulting in antimicrobial drug resistance. This fine-tuned, Rdrp2-dependent RNAi activity is critical for genome stability, restricting GremLINE1 retroelements to the centromeres where they occupy long heterochromatic islands. Taken together, our results suggest that RNAi and heterochromatin formation are independent genome defense and regulatory mechanisms in the Mucorales, contributing to a paradigm shift from the cotranscriptional gene silencing observed in fission yeasts to models in which heterochromatin and RNAi operate independently in early-diverging fungi.
Background. Postponed coronavirus infection (COVID-19), accompanied by an immunosuppressive state and associated with the risk of secondary diseases such as mucormycosis. Diabetes mellitus is an independent risk factor for both severe COVID-19 and mucormycosis. Aims our aim was to experience the diagnosis and treatment of rhino-orbitocerebral mucormycosis in post-COVID-19 patients. Materials. A single-center, observational, non-randomized, cohort comparative study was conducted. We assessed the clinical features, risk factors, diagnosis and outcomes of mucormycosis among recovered COVID-19 patients with hospitalisation in the otorhinolaryngology department of the Samara State Medical University Clinics, Samara, from SeptemberDecember 2021. CT examinations were performed on Revolution EVO CT scanner (GE, Russia) and MRI on Aera MR scanner 1.5 T (Siemens, Germany). Materials for microbiological and histopathological examination were taken from all examined patients intraoperatively. Results. The experience of diagnosing and treating rhinoorbitocerebral mucormycosis in patients after a new coronavirus infection was analyzed, the influence of the complex use of radiation diagnostic methods, histopathological and microbiological methods on the development and effectiveness of mucormycosis treatment was determined. Conclusions. The effectiveness of disease management directly depends on the early initiation of etiotropic treatment, while the role of complex radiological diagnostics, histopathological and microbiological methods is important for early confirmation of the fungal etiology of the disease.
We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock. Moreover, case reports of pulmonary mucormycosis in children published since 1959 were reviewed. In summary, metagenomic next-generation sequencing is an effective diagnostic method for Cunninghamella with high speed and sensitivity.
Mucormycosis started during COVID 19 when patients were treated with number of steroids oxygen, that further lead to increase in diabetes mellitus which was main cause of mucormycosis increase in black fungus further caused rhino-orbito-cerebral mucormycosis and angio invasive behavior of fungal hype that is from Mucoraceae family is main cause of the infection increases rapidly also damages the facial tissues vigorously uncontrolled diabetes, immunosuppressive, steroids poor glycemic control are main causes MRI is a technique that is been used for observing the growth of fungal hype from Epidermiological data its been proven that the mucormycosis is been spreading in countries such as India, Nepal, and Bangladesh rapidly its serious health concern in future.
Background:
A variety of bacterial and fungal co-infections may be attributed to the coronavirus disease 2019 (COVID-19), particularly in people who already have a medical condition such diabetes mellitus or those who received large dosages of steroids.
Case report:
We described a 52-year-old diabetic man who was receiving high doses of dexamethasone and antibiotics while receiving ambulatory care for COVID-19 pneumonia. His anterior rhinoscopy revealed a necrotic scab, and a sample confirmed Mucor spp. He underwent surgery and was given amphotericin as a result of the severity of the condition, palpebral ptosis, and right ocular palsy he was experiencing. The patien ́s progression was satisfactory.
Conclusions:
pre-existing diabetes mellitus, previous steroid and antimicrobial use, as well as SARS-CoV-2 infection are some of the risk factors associated with Mucor spp. infection. Prompt detection of mucormycosis is important in the management of these affected patients.
Purpose:
The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019.
Design:
A nonrandomized retrospective case-control study.
Methods:
The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors.
Results:
A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group.
Conclusions:
Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.
Procedures such as solid-organ transplants and cancer treatments can leave many patients in an immunocompromised state. This leads to their increased susceptibility to opportunistic diseases such as fungal infections.
Background:
Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS.
Methods:
The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated.
Results:
Review and evaluation of published literature was performed on twelve topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains.
Conclusion:
Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms. This article is protected by copyright. All rights reserved.
Objectives:
This analysis evaluated the variability of isavuconazole plasma concentrations between subjects and between sampling times, and assessed their relationship to outcomes for subjects with invasive fungal disease (IFD) in the SECURE trial.
Methods:
Isavuconazole-treated subjects received 372 mg of isavuconazonium sulphate (corresponding to 200 mg of isavuconazole) three times daily for 2 days, then once daily. Plasma samples were collected after day 4 and analysis sets were constructed as follows: analysis set 1 included all samples from subjects with proven/probable/possible IFD who received ≥1 dose of isavuconazole; analysis set 2 included samples from subjects in analysis set 1 who had provided >1 sample; and analysis set 3 included samples from subjects in analysis set 1 with proven/probable invasive aspergillosis. Assessments included overall distributions of plasma concentrations and variability between samples (analysis sets 1 and 2) as well as relationships to outcomes [all-cause mortality (day 42), overall response (end of treatment) and treatment-emergent adverse events; analysis sets 1 and 3].
Results:
Analysis sets 1, 2 and 3 included samples from 160, 97 and 98 subjects, respectively. Trough concentrations for each were distributed similarly [mean (SD): 3406.6 (1511.5), 3495.6 (1503.3) and 3368.1 (1523.2) ng/mL, respectively]. The mean coefficient of variation between samples in analysis set 2 was 23.2%; differences between concentrations in first samples and subsequent samples were <2-fold for 85/97 subjects. In quartiles of subject data, no concentration-dependent relationships were observed for efficacy or safety.
Conclusions:
Plasma concentrations of isavuconazole were reasonably consistent between subjects and sampling times, and were not associated with differences in outcomes.
Isavuconazole may be useful in treating and preventing fungal infections in solid organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales . Isavuconazole has favourable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady state pharmacokinetics of Isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate inter-patient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for area under the plasma concentration-time curve (AUC) and 59% for trough plasma concentration), which were in general less than previously reported for other mould-active azoles such as voriconazole and posaconazole. AUC and steady state trough plasma concentrations (C trough ) were significantly lower in women, patients with body mass index ≥18.5 kg/m ² , and those receiving hemodialysis. Trough plasma concentrations were highly-correlated with AUCs (R ² =0.94), and can serve as suitable measure of isavuconazole exposure in patients. In conclusion, moderate inter-patient variability in isavuconazole exposure, identification of factors associated with lower exposure, recognition that C trough is a surrogate marker for AUC and availability of a simple analytical method, suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients’ clinical outcomes, and to determine the clinical role of TDM.
Invasive fungal wound infections (IFIs) were an unexpected complication associated with blast-related wounds during Operation Enduring Freedom. Between 2010 and 2012, IFI incidence rates were as high as 10–12% for patients injured during Operation Enduring Freedom and admitted to the intensive care unit at the Landstuhl Regional Medical Center. Independent risk factors for the development of IFIs include dismounted blast injuries, above knee amputations and massive (>20 units) packed red blood cell transfusions within 24 hours after injury. The Joint Trauma System developed a Clinical Practice Guideline on IFI prevention, identification and management. Aggressive and frequent surgical debridement remains the primary therapy accompanied by topical antifungal therapy (e.g., Dakins solution). Empiric systemic antifungal therapy with both liposomal amphotericin B and an intravenous broad-spectrum triazole (e.g., voriconazole or posaconazole) should be administered when there is strong suspicion of IFI based on the occurrence of recurrent wound necrosis following serial surgical debridements, since many cases involve multiple fungal species. Other recommendations include: (1) early tissue sampling for wound histopathology and fungal cultures, (2) early consultation with infectious disease specialists, and (3) coordination with surgical pathology and clinical microbiology.
Purpose
Mucormycosis (MCM) is a rare fungal infection affecting people with impaired immunity. Data related to MCM from Lebanon are scarce. The aim of this study is to shed light on the epidemiology, incidence, and outcome of patients with MCM hospitalized at a tertiary care center in Lebanon.
Methods
We conducted a retrospective chart review between Jan 1, 2008 and Jan 10, 2018. All patients with proven or probable MCM were included.
Results
A total of 20 patients were included. Their median age was 49 years and the majority were males. Comorbidities included mainly hematologic malignancy and diabetes mellitus. Most common sites of involvement were rhino-orbital and pulmonary, respectively. The number of MCM cases/10.000 hospital admissions increased significantly between 2008 and 2017 (0.47 vs. 1.18; P < 0.05). A liposomal amphotericin B formulation alone or in combination with other antifungals was used as a first line agent in all patients. All-cause mortality was 60%; however, death was attributed to MCM in 20% of cases.
Conclusion
The incidence of MCM has significantly increased over the past 10 years at our institution, most likely due to the increasing patient population at risk. Understanding the epidemiology of MCM in our setting would help guide antifungal therapy.
Link to full online version: https://rdcu.be/4MFf
Mucormycosis due to Mucorales is reported at large numbers in uncontrolled diabetics across India, but systematic multicenter epidemiological study has not been published yet. The present prospective study was conducted at four major tertiary care centers of India (two in north and two in south India) during 2013-2015 to compare the epidemiology, treatment strategies and outcome of mucormycosis between the two regions. Molecular techniques were employed to confirm the identity of the isolates or to identify the agent in biopsy samples. A total of 388 proven/probable mucormycosis cases were reported during the study period with overall mortality at 46.7%. Uncontrolled diabetes (n = 172, 56.8%) and trauma (n = 31, 10.2%) were the common risk factors. Overall, Rhizopus arrhizus (n = 124, 51.9%) was the predominant agent identified, followed by Rhizopus microsporus (n = 30, 12.6%), Apophysomyces variabilis (n = 22, 9.2%) and Rhizopus homothallicus (n = 6, 2.5%). On multivariate analysis, the mortality was significantly associated with gastrointestinal (OR: 18.70, P = .005) and pulmonary infections (OR: 3.03, P = .015). While comparing the two regions, majority (82.7%) cases were recorded from north India; uncontrolled diabetes (n = 157, P = .0001) and post-tubercular mucormycosis (n = 21, P = .006) were significantly associated with north Indian cases. No significant difference was noted among the species of Mucorales identified and treatment strategies between the two regions. The mortality rate was significantly higher in north Indian patients (50.5%) compared to 32.1% in south India (P = .016). The study highlights higher number of mucormycosis cases in uncontrolled diabetics of north India and emergence of R. microsporus and R. homothallicus across India causing the disease.
Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. These methods lack sensitivity, and are most definitive later in the course of infection resulting in prevention of timely intervention. PCR-based approaches have promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding CotH genes are uniquely and universally present among Mucorales. Thus, CotH genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether CotH could be PCR-amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay. CotH was detected as early as 24 h post infection in plasma, urine and bronchoalveolar lavage (BAL) from mice infected intratracheally with Rhizopus delemar, R. oryzae, Mucor circinelloides, Lichtheimia corymbifera, or Cunninghamella bertholletiae but not from samples taken from uninfected mice or those infected with Aspergillus fumigatus . Detection of CotH from urine samples was more reliable than from plasma or BAL. Using the Receiver Operating Characteristic (ROC) method, the sensitivity and the specificity of the assay was found to be 90% and 100%, respectively. Finally, CotH was PCR-amplified from urine samples of patients with proven mucormycosis. Thus, PCR-amplification of CotH is a promising target for a reliable, sensitive and simple method of early diagnosis of mucormycosis.
Rationale:
Cutaneous mucormycosis is an uncommon disease and occurs rarely in immunocompetent patients.
Patient concerns:
We reported the case of a 37-year-old man presenting with a skin lesion on the left side of the chest wall with no history of trauma or primary diseases. He was firstly misdiagnosed as tuberculosis and the proper treatment was thus delayed.
Diagnoses:
Histopathological examination and fungal culture of the lesion confirmed cutaneous mucormycosis. The isolate was identified as Rhizopus microspores by ITS sequencing.
Interventions:
The patient was treated with oral posaconazole 400 mg bid for 150 days.
Outcomes:
The patient recovered satisfactorily. No recurrence was found during the follow-up and no side effect of liver function was found.
Lessons:
This case helps doctors to consider the possibility of serious fungal infection in immunocompetent patients. It also suggested that posaconazole could be an alternative choice for the treatment of mucormycosis considering the severe side effect of Amphotericin B.
This study investigated the epidemiology and risk factors associated with invasive fungal infections (IFIs) during induction chemotherapy in a cohort of Taiwanese patients with newly-diagnosed acute myeloid leukemia (AML). IFIs are a significant complication in the management of immunocompromised cancer patients; such infections are associated with a high incidence of morbidity and mortality, particularly in many South-Asian countries, where IFI rates are increasing. We retrospectively analyzed IFI incidence data from 105 patients with newly diagnosed AML at a single center undergoing their first course of induction chemotherapy without primary antifungal prophylaxis between November 2008 and December 2014. Of 21 cases documented as proven/provable IFIs 16 (76%) were invasive aspergillosis, 2 (10%) were mucormycosis infections, and 3 (14%) were proven yeast infections. The lung was the most commonly affected site (n = 16; 76%); 2 patients (10%) developed fungal sinusitis. IFI cases were more often males (P = 0.020). In multivariate analysis, patients with neutropenia lasting>30 days were more than twice as likely to develop IFI (OR, 2.24 [95% CI, 2.81–31.11], P<0.001). We also confirmed patients with smoker and receiving parenteral nutrition during chemotherapy were significant associated with IFIs. Our findings suggest that antifungal prophylaxis should be considered for patients with AML during induction chemotherapy, particularly in patients from Southeastern Asia, an area of potentially high IFI rates. We recommend that clinicians determine which patients receiving induction chemotherapy for AML are at high risk of developing IFI, to allow for targeted therapeutic prophylaxis.
The diagnosis of gastrointestinal (GI) mucormycosis is always a challenge due to its non‐specific clinical presentations and often diagnosed at autopsy. Recently increased number of GI mucormycosis has been reported in immunocompetent hosts and during 1948 through 2017, 200 cases of GI mucormycosis are available in literature. We could review 176 cases where case details were available. Majority (50.6%) of the cases were reported from Asia. The disease in nearly equally recorded in adults and paediatric population. The infection commonly affected the intestine (64.2%) followed by stomach (33%). A significant improvement in ante‐mortem diagnosis was noted since 2001. Rhizopus species were the predominant (67.5%) etiologic agents. Amphotericin B was the most commonly used drug (93.4%). Despite improvement of ante‐mortem diagnosis and therapy, the mortality was 60.5% and 67.5% in adults and children respectively. Combined medical and surgical therapy (reported in 47.8% patients) had significantly better survival rate than those receiving either of them. Analysing the clinical presentations, we propose to suspect GI mucormycosis in a malnourished/ dehydrated child (especially premature neonate) with history of exposure to broad‐spectrum antibiotics or formula/spoon feeding and presenting with mass in abdomen, abdominal distension or bilious vomiting; and an adult presenting with abdominal distension, fever or GI bleed with underlying risk factors for mucormycosis.
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Mucormycosis is an aggressive fungal infection caused by zygomycetes from the order of Mucorales. Immunocompromised patients or patients with comorbidities are susceptible to this infection. There are many forms of mucormycosis such as rhino-orbito-cerebral, cutaneous, gastrointestinal, and pulmonary. Cutaneous mucormycosis is rare in trauma patients with no comorbidities. Morel-Lavallée lesions are rare degloving injuries in trauma patients. We report a case of cutaneous mucormycosis in a trauma patient with the Morel-Lavallée lesions. © 2018 Indian Journal of Critical Care Medicine | Published by Wolters Kluwer - Medknow.
Ascomycetes and zygomycetes account for the majority of (i) fungi responsible for cutaneous, subcutaneous, and invasive human fungal infections, (ii) plant fungal pathogens, (iii) fungi that threaten global biodiversity, (iv) fungal agents of agricultural spoilage, and (v) fungi in water-damaged buildings. Rapid recognition of fungal infection (or contamination) enables early treatment (or remediation). A bioinformatics search found homologues of Saccharomyces cerevisiae Mnn9p present in members of the Zygomycota and Ascomycota phyla and absent in members of the Chytridiomycota and Basidiomycota. Mnn9p is a component of the yeast mannan polymerization complex and is necessary for α-1,6 mannan production. A monoclonal antibody (2DA6) was produced that was reactive with purified mannans of Mucor, Rhizopus, Aspergillus, Fusarium, and Candida species. Experimentation using a 2DA6 antigen capture enzyme-linked immunosorbent assay (ELISA) and extracts of fungi from the four phyla found agreement between the presence or absence of Mnn9p homologues and production or lack of production of mannan reactive with 2DA6. Studies of cell extracts from yeast mannan mutants identified α-1,6 mannan as the epitope recognized by 2DA6. To translate this finding into a point-of-use diagnostic, a 2DA6 lateral flow immunoassay was constructed that detected mannan in (i) extracts of dermatophytes and fungi that produce traumarelated infection and (ii) tissue from plants infected with Grosmannia clavigera or Sclerotium cepivorum. These studies (i) revealed that the conservation of α-1,6-linked mannan in fungi of the Zygomycota and Ascomycota can be exploited as a broad diagnostic target and (ii) have provided a means to detect that target in an immunoassay platform that is well suited for clinic or field use.
Mucormycosis is an invasive mold infection, frequently fatal in immunocompromised patients. We report the case of a patient with chronic lymphocytic leukemia admitted to the hematology unit for febrile aplasia. Pulmonary lesions suggesting a fungal infection expanded/increased despite a combination of posaconazole and liposomal amphotericin B. The fungal biomarkers performed repeatedly were negative. At D65 after chemotherapy a bronchial biopsy was positive for Cunninghamella bertholletiae. The patient died despite appropriate antifungal management. A qPCR targeting Cunninghamella was developed a posteriori, and a retrospective analysis showed that a sample was positive more than 30 days before culture-based identification could be made.
Mucorales are ubiquitous environmental molds responsible for mucormycosis in diabetic, immunocompromised, and severely burned patients. Small outbreaks of invasive wound mucormycosis (IWM) have already been reported in burn units without extensive microbiological investigations. We faced an outbreak of IWM in our center and investigated the clinical isolates with whole-genome sequencing (WGS) analysis. We analyzed M. circinelloides isolates from patients in our burn unit (BU1, Hôpital Saint-Louis, Paris, France) together with nonoutbreak isolates from Burn Unit 2 (BU2, Paris area) and from France over a 2-year period (2013 to 2015). A total of 21 isolates, including 14 isolates from six BU1 patients, were analyzed by whole-genome sequencing (WGS). Phylogenetic classification based on de novo assembly and assembly free approaches showed that the clinical isolates clustered in four highly divergent clades. Clade 1 contained at least one of the strains from the six epidemiologically linked BU1 patients. The clinical isolates were specific to each patient. Two patients were infected with more than two strains from different clades, suggesting that an environmental reservoir of clonally unrelated isolates was the source of contamination. Only two patients from BU1 shared one strain, which could correspond to direct transmission or contamination with the same environmental source. In conclusion, WGS of several isolates per patients coupled with precise epidemiological data revealed a complex situation combining potential cross-transmission between patients and multiple contaminations with a heterogeneous pool of strains from a cryptic environmental reservoir.
Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. With this review, we aim to summarize current knowledge regarding the recognition and clinical presentation of IFD in neonates and children.
Background
The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown.
Objectives
To document the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species.
Patients/Methods
VITAL was a single‐arm, international, open‐label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs. The primary outcome was overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by multiple fungal species.
Results
Fifteen patients were included in this analysis (including Aspergillus spp., n=11; without Aspergillus spp., n=4; median treatment duration [range], 97 [6–544] days). Overall treatment success was observed in 2/15 patients (13.3%) at Days 42 and 84, and 2/14 (14.3%) at EOT. All‐cause mortality was 2/15 (13.3%) at Day 42 and 4/15 (26.7%) at Day 84. All patients had ≥1 treatment‐emergent adverse event (TEAE); 12 patients (80.0%) had serious TEAEs; TEAEs led to discontinuation of isavuconazole in two patients (13.3%).
Conclusions
Isavuconazole may be useful to treat some IFDs caused by multiple fungal species.
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The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
Mucormycosis is a rare, fulminant, rapidly spreading fungal infection, which usually affects patient with underlying immune deficiency. If not managed promptly, the disease is characterized by progressive necrosis and is often fatal. A review of English literature shows that only fourteen cases of mucormycosis have been reported after tooth extraction. This paper highlights two cases of mucormycosis subsequent to tooth extraction in healthy adult patients. This first patient presented with an oroantral fistula and extensive maxillary necrosis. Whereas the second case was localized and presented as non-healing extraction socket with alveolar necrosis. This adds two more cases of this rare and serious complication of tooth extraction, to the present literature.
Key words:Fungal, infection, zygomycosis, exodontia, complication, jaw, necrosis.
Mucormycosis, also known as zygomycosis, is an aggressive infection caused by a ubiquitous group of molds known as mucormycetes and is often associated with immune suppression or trauma among immunocompetent populations. We present the case of a 19-year-old woman who was involved in a motor vehicle accident in whom rapidly progressive invasive cutaneous facial mucormycosis subsequently developed. The diagnosis, treatment options, and incidence of this disease process are discussed in the context of trauma.
Background/purpose:
This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy.
Methods:
All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus.
Results:
During the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P < 0.001), and admission to the intensive care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P = 0.022) based on multivariate analysis.
Conclusion:
Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.
Mucormycosis is a rare, opportunistic fungal infection that occurs almost exclusively in immunocompromised hosts such as patients with diabetes mellitus, leukemia, lymphoma, renal disease, septicemia, burns, malnutrition, and following long-term treatment with steroids and antibiotics. Based on the clinical presentation and involvement, mucormycosis is classified as six major forms, namely, rhinocerebral, pulmonary, cutaneous, gastrointestinal (GI), disseminated and miscellaneous, with rhinocerebral and pulmonary being the common forms. GI mucormycosis is rare, accounting for only 7% of all cases; however, the mortality rate is as high as 85%. Here we report a case of a young immunocompetent male who developed gastric invasive mucormycosis during an acute illness and succumbed to it despite all supportive care.
Mucormycosis is a rare and acute fungal infection which is frequently lethal, usually observed in non-controlled diabetic patients. The infection usually begins in the nose but it can invade the lung, the digestive tract, and the skin. Rhinocerebral mucormycosis accounts for 40 to 49% of mucormycosis cases. We report the case of a 44-year-old diabetic man, presenting with rhinocerebral mucormycosis. Our patient was treated by an association of amphotericin B and surgical debridement.
Invasive fungal rhinosinusitis (FRS) is a potentially fatal illness requiring early diagnosis
and aggressive treatment with surgery and antifungals. We report a case of chronic FRS in a
recently diagnosed diabetic individual due to Curvularia lunata. Imaging revealed extension
into the right orbit and right basifrontal lobe. This was further complicated by development
of nosocomial mucormycosis which was attributed to voriconazole therapy. The patient
responded well to debridement and amphotericin B based therapy. To our knowledge,
there are no reported cases of invasive FRS due to Curvularia lunata. Also, breakthrough
mucormycosis on voriconazole therapy is rarely seen in non-malignancy, non-transplant
settings. The possibility of rare fungal infections (community and nosocomial) should be
entertained in developing settings where fungal spores are ubiquitous.
Thalassemia is a group of genetically inherited hemoglobin (Hb) disorders characterized by reduced synthesis of the b-globin chain and a sub-sequent imbalance in the a/b-globin chain ratio that results in chronic hemolytic anemia. The severity of clinical phenotype is used to distinguish this heterogeneous disease in two main subtypes: Thalassemia Major (TM) and Thalassemia Intermedia (TI). Iron overload is mostly due to increased intestinal absorption because of chronic anemia. Transfusions, in contrast with what happens in TM, have a minor role in the development of iron overload. However, although 1-year data from the phase 2, prospective, randomized, double-blind, placebo-controlled trial and 1-year extension results from the THALASSA study assessing the efficacy and safety of deferasirox in TI patients with iron overload have been reported, no data, during randomized trials, have been so far published on Deferiprone (DFP) treatment (Taher et al Blood 2012 and Ann Hematol 2013)
Adult patients with TI were randomly assigned in permuted blocks of 10 with a ratio 1:1 to DFP at 75 mg/kg/day for 7 d/week divided into three oral daily doses (DFP-group) or DFO by sc infusion (8–10 h) at 50 mg/kg per day for 5 d/week (DFO-group). The study was designed to detect an improvement in decreasing mean serum ferritin levels in each of the treated-groups from the initiation of therapy to each year (from year 1 to year 5) with a significance level of 5% and 80% power. The planned number of subjects was between 40 and 100 (Rochon Biometrics 1991).
The primary endpoint was the treatment efficacy evaluated as change from the baseline value in serum ferritin levels during the 5 years assessed using a linear mixed-effects model (LMM, Laird-Ware Biometrics 1982) where we assumed the patient effect (given by the intercept terms for each patient) as random effect, while the treatment effect (treat), the time effect (time), the treatment-by-time interaction effect (treat×time), and the total transfusions in ml (tot TX) as fixed effects. Secondary endpoints were safety and survival analysis at 5-years evaluated considering the number of advers events and Kaplan-Meir curves respectively.
Overall 88 patients, observed at 12 SoSTE centers in Italy between January 2001 and May 2011, were randomized (47 DFP-group and 41 DFO-group). There were no differences observed at baseline between the two randomized groups in clinical and haematological findings.
The regression coefficient of time suggested that there was a linear decrease over time in the mean serum ferritin levels in both treatment-groups even if the p-value was very close to the statistical significance (Coeff. -88.4, 95% CI (-182.4; 5.6), p-value =0.065). However, the mean serum ferritin levels did not seem to be significantly different between the two treatment-groups over time (Coeff. -77.4, 95% CI (-231.7; 77.1), p-value=0.326 ). The effect of total blood transfusion on serum ferritin levels was not statistically significant (Coeff. 0.06, 95% CI (-0.01; 0.1), p-value=0.100). The estimated profiles of serum ferritin levels in the two groups were represented in Figure I.
Agranulocytosis was reported in 4 case of DFP versus no cases of DFO group, respectively (p-value=0.118). Neutropenia was statistically significant different between the two groups DFP (6 (12.5%) versus no cases in DFO , p-value=0.027).
Kaplan-Meier survival probability curves for the two treatment groups are shown in Figure II, and the log-rank test did not show any statistically significant difference in the survival between the two groups (p-value=0.36).
In conclusion, these findings suggest as DFP shows same effectiveness and survival probability versus DFO with controlled safety profile. Therefore, these results support the possibility of using this drug in TI patients in which DFO and Deferasiorx is contraindicated.
Figure I: Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model. Figure I:. Estimated profiles of the mean serum ferritin in the two treatment-groups from the fitted linear mixed-effects model.
Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36). Figure II. Kaplan–Meier survival probability curves in the two treatment groups during multi-center TI clinical trial (DFP: continous line; DFO: dashed line), (p-value=0.36).
Disclosures
No relevant conflicts of interest to declare.
The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk factors. The Entomophthorales are closely related to the Mucorales on the basis of sexual growth by production of zygospores and by the production of coenocytic hyphae. Despite these similarities, the Entomophthorales and Mucorales have dramatically different gross morphologies, asexual reproductive characteristics, and disease manifestations. In comparison to the floccose aerial mycelium of the Mucorales, the Entomophthorales produce a compact, glabrous mycelium. The asexually produced spores of the Entomophthorales may be passively released or actively expelled into the environment. Human disease with these organisms occurs predominantly in tropical regions, with transmission occurring by implantation of spores via minor trauma such as insect bites or by inhalation of spores into the sinuses. Conidiobolus typically infects mucocutaneous sites to produce sinusitis disease, while Basidiobolus infections occur as subcutaneous mycosis of the trunk and extremities. The Entomophthorales are true pathogens, infecting primarily immunocompetent hosts. They generally do not invade blood vessels and rarely disseminate. Occasional cases of disseminated and angioinvasive disease have recently been described, primarily in immunocompromised patients, suggesting a possible emerging role for this organism as an opportunist.
Background
Posaconazole (PCZ) is widely used for prophylaxis or treatment of invasive fungal infections (IFIs) in leukemia patients. However, issues with PCZ tolerability can result in treatment interruption. Isavuconazole (ISA) has a similar broad spectrum of activity to PCZ, however real‐world data regarding the tolerability of ISA after PCZ toxicity are lacking.
Objectives
To describe the tolerability of ISA after PCZ toxicity in leukemia patients.
Patients/Methods
We retrospectively assessed tolerability of ISA after PCZ toxicity in adult leukemia patients (March 2015 to November 2017). We included all patients who received > 7 days of ISA within 48 hours of PCZ discontinuation. Laboratory markers for liver toxicity were collected at three time points: prior to PCZ, at switch to ISA, and after ISA therapy.
Results
We identified 23 such patients. Increased liver function tests (LFTs) were noted in 20 patients on PCZ, while 3 patients had Grade 3/4 QTc prolongation. No patient discontinued subsequent ISA due to toxicity. Grade 3/4 elevations in LFTs were decreased after changing to ISA (30% after PCZ vs. 5% after ISA). No patient had significant QTc prolongation after switching to ISA.
Conclusions
ISA was well‐tolerated in patients discontinuing PCZ due to toxicity, with no patient discontinuing ISA due to toxicity.
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Cutaneous mucormycosis is a rare disease which caused by opportunistic fungi, which usually affects patients with immunosuppression. Mucor irregularis is a distinctive pathogenic fungi in Mucorales which prevails in China, unlike common mucormycosis, it mostly involves in non‐immunocomprised individuals.[1] Gene deficiency of patients with cutaneous Mucormycosis has never been reported to our knowledge.
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Mold specific T-cells have been described as a supportive biomarker to monitor invasive mycoses and mold exposure. This study comparatively evaluated frequencies and cytokine profiles of Aspergillus fumigatus and Mucorales reactive T-cells depending on environmental mold exposure. Peripheral blood mononuclear cells (PBMCs) obtained from 35 healthy donors were stimulated with mycelial lysates of A. fumigatus and three human pathogenic Mucorales species. CD154+ specific T-cells were quantified by flow cytometry. In a second cohort of 20 additional donors, flow cytometry was complemented by 13-plex cytokine assays. Mold exposure of the subjects was determined using a previously established questionnaire. Highly exposed subjects exhibited significantly greater CD154+A. fumigatus and Mucorales specific naïve and memory T-helper cell frequencies. Significant correlation (r = 0.48 - 0.79) was found between A. fumigatus and Mucorales specific T-cell numbers. Logistic regression analyses revealed that combined analysis of mold specific T-cell frequencies and selected cytokine markers (A. fumigatus: IL-5 and TNF-α, R. arrhizus: IL-17A and IL-13) significantly improves classification performance, resulting in 75-90 % predictive power using 10-fold cross-validation. In conclusion, mold specific T-cell frequencies and their cytokine signatures offer promising potential in the assessment of environmental mold exposure. The cytokines identified in this pilot study should be validated in the clinical setting, e. g. in patients with hypersensitivity pneumonitis.
Background
Accurate diagnosis of mucormycosis, a life‐threatening fungal infection, remains a challenge for physicians.
Objectives
To identify the causative Mucorales in fresh clinical samples and formalin‐fixed paraffin‐embedded (FFPE) samples of patients with proven mucormycosis by molecular method.
Patients/Methods
Fresh clinical samples of patients with proven mucormycosis according to the EORTC/MSG criteria admitted between 2015 and 2017 and histopathologically proven FFPE archives collected during 2004‐2007 and 2015‐2017 from Mazandaran University‐affiliated hospitals of northern Iran were included. Semi‐nested PCR targeting the 18S rDNA of Mucorales and ITS region was performed and PCR products were then sequenced.
Results
While culture was positive only in 5 of 9 (56%) of fresh specimen cases, PCR was positive in all 9 (100%) histologically proven mucormycosis. Ten of 18 (56%) FFPE samples were PCR‐positive. Overall, Mucorales PCR was positive in 19 of 27 (70%) samples. Mucorales species were Rhizopus arrhizus in 16 (84%) cases, Rhizopus arrhizus / Amylomyces rouxii in 2 (10.5%) cases and Rhizopus stolonifer in one case (5.5%). Among 27 mucormycosis cases, 25 (93%) cases were rhinocerebral, and 2 (7%) disseminated. Diabetes mellitus (74%) and neutropenia (63%) were the main risk factors.
Conclusions
Semi‐nested PCR targeting 18S rDNA region of Mucorales is useful for identification of the causative agents of mucormycosis.
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