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Objectives: Mucormycosis is a rare invasive fungal infection with high lethality, affecting mainly patients with hematological neoplasia, decompensated diabetes, and covid-19 infection. The aim was to perform a cost-effectiveness analysis of liposomal Amphotericin B (standard treatment) versus isavuconazole for treating mucormycosis in the consolidation phase from the perspective of the Brazilian Unified Health System. Method(s): A decision tree model was built. The analysis considered the costs of the treatment over a six-month time horizon. This included hospitalization during the entire course of treatment and the expenditures related to dialysis, complication occurring in 5% (3%-6%) of cases treated with the Amphotericin B. Appointments with specialists were included in the isavuconazole arm, and amphotericin B was used if the patient failed to respond to isavuconazole. The utility of the patient with mucormycosis, cured and with renal failure was estimated. Uncertainties were assessed through probabilistic and deterministic sensitivity analyses. Result(s): The average cost of amphotericin B and isavuconazole arm was R$1.054.874,39 and R$522.344,05, respectively. The utility was 0.479 with amphotericin B and 0.480 with isavuconazole. The ICER was R$ -684,494,237 (dominant). In deterministic sensitivity analysis, the probability of dialysis was the variable with the greatest impact. In probabilistic analysis, the ICER is distributed in the right and left lower quadrant, the acceptability curve for all the scenarios analyzed is favorable for isavuconazole. The budget impact suggests a potential savings of between R$ 350 million and R$ 415 million over five years. Conclusion(s): The treatment of mucormycosis during the consolidation phase with isavuconazole represents a lower cost, besides the convenience of oral treatment and reduced incidence of severe adverse events, with mortality similar to the Amphotericin B arm. In Brazil, the formulation of posaconazole approved is inadequate for treating mucormycosis during the consolidation phase, therefore isavuconazole is the single oral drug available.Copyright © 2023
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Background: The combination of venetoclax and azacitidine was licensed as a treatment regime for AML during the COVID-19 pandemic and has only been available for a short period of time. It has been widely adopted, including by our centre, for use in older adults and those with multiple co-morbidities, for whom intensive treatment might not be appropriate, but where low-intensity treatment or palliative care is also considered inappropriate. We feel that our patient cohort has been experiencing a lot of cytopaenias with the regime and thus treatment has been de-escalated more commonly than seen in the VIALE-A trial1 and so decided to carry out an audit of our practice. Method(s): Patients were identified by our pharmacy colleagues as having had Blueteq forms completed for venetoclax-azacitidine treatment. We then looked at their electronic medical records to ascertain their age, co-morbidities, treatment received, any treatment modifications made (and reasons for these adjustments), disease course and time until death. Result(s): We identified 22 patients who have received treatment with venetoclax and azacitidine, since October 2020. Eleven of these patients are now deceased (50%), with causes of death attributable to progressive disease or infection. The median age of our patient population was 72 years old (range of 51-84). The maximal number of cycles of venetoclax-azacitidine that have been delivered to a single patient is 12 (with cessation following disease progression). 9/22 patients had no dose modifications made to treatment, but of these, six patients only received one cycle of treatment (prior to progressive disease or death from sepsis). The rest of the patients (13) have had dose reductions to shorter courses of venetoclax (to between 21 days and 7 days) or have been changed to azacitidine alone (5/13 patients). One of our 22 patients has now received an allograft. Conclusion(s): Our patients routinely receive posaconazole prophylaxis, and thus a dose of 100 mg venetoclax (due to the known interaction), rather than the 400 mg dose used in the VIALE-A trial1-it may be that this, (and that it is equivalent to an actual dose of greater than 400 mg), is the reason behind the increased incidence of cytopaenias and increased need to de-escalate treatment. In the future it would be helpful and informative to compare our practice to that of other centres.
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Background: Post-Covid retropharyngeal mucormycosis is a rare presentation, and no case has been reported in literature until date. Case presentation: A-32-year-old female post Covid presented to our OPD with history of dysphagia and with a history of steroid intake. Radiology confirmed it as retropharyngeal abscess. Endoscopic-guided aspiration was done. HPE (histopathological examination) revealed classic broad aseptate hyphae of mucormycosis. Patient was managed conservatively with broad-spectrum antifungal. Conclusion(s): Retropharyngeal mucormycosis is a rare entity in Covid era. Rapid diagnosis and management are needed to save life of an individual, or results could be fatal.Copyright © 2022, The Author(s).
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Invasive Aspergillosis of the paranasal sinus is an aggressive illness, particularly affecting the immunocompromised and rarely, the immunocompetent. COVID-19 has been shown to cause a derangement of immune parameters both during active infection and the convalescent period. A retrospective study was done from June 10th 2021 to September 10th 2021 on patients who underwent endoscopic debridement of the involved sinuses for post COVID fungal rhinosinusitis. This study included the patients who had Aspergillus infection from the isolated nasal tissue samples. Patient's information, complaints, history of COVID infection, clinical findings, investigations and treatment details were obtained from the records. 13 patients with post-COVID Invasive Fungal Sinusitis were identified. Symptom onset usually occurred within 1 month of COVID 19 diagnosis in all the patients. Nasal obstruction (84%) and headache (61%) were the most common symptoms. Computerized tomography imaging showed maxillary sinus involvement in all patients followed by ethmoid sinus in 76% of patients. Microbiological diagnosis and histopathological confirmation of Aspergillus species was done. All 13 patients underwent endoscopic debridement of the involved sinuses followed by anti-fungal therapy with Posaconazole. All responded well to the treatment with no recurrence till date. Admist an infinite number of Mucormycosis cases in this era of COVID-19 pandemic, we experienced a surge of Aspergillus infection during this second wave. Presentation at a young age, with no known co-morbidities, with minimal symptoms and history of COVID-19 infection are some of the important aspects to be considered in this series. A better morbidity outcome is expected when early detection and treatment is made in patients with post Covid-19 viral illness with Aspergillosis of nose and paranasal sinus.
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Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens - isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Mucormycosis is an angioinvasive opportunistic fungal infection, but these have become emerging pathogens, especially in conditions with underlying predisposing risk factors in a favourable setting. With the exponential rise in COVID-19 cases, there was an increase in the number of mucormycosis cases among them. The global prevalence rate of mucormycosis in COVID-19 globally varies from 0.005 to 1.7 per million population and in India, it is approximately 0.14 cases/1000. The objective of this study is to detect the prevalence of mucormycosis with the antifungal susceptibility pattern among COVID-19 patients admitted in our hospital. A total of 347 COVID-19 and post-COVID-19 patients with symptoms suggestive of mucormycosis were included in this study. Nasal scrapings, debrided necrotic tissue, unhealthy tissue bits and biopsy tissues taken through FESS were processed for mycological examination under sterile conditions. Among the total 347 samples processed, 87(25%) were positive for fungal culture. Among the culture positves 7.8% (25) belong to mucorales. Among the total 87 fungal isolates, the majority of organism isolated was Aspergillus sp(68%), followed by Rhizopus sp (18%). Rhizopus/Aspergillus sp (5%), Mucor species (5%), Rhizomucor sp (2%), Mucor/Aspergillus sp(1%), Curvularia sp (1%) were the other fungi isolated. All the strains of Mucorales were sensitive to Posaconazole and one strain showed resistance to amphotericin B with MIC 8 microg/ml by microbroth dilution method based on CLSI M27 guidelines for Amphotericin B, and Posaconazole.Copyright © The Author(s) 2023.
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Background: Mucormycosis is a fungal infection caused by filaments of Mucoraceae which invades blood vessels culminating in a lethal opportunistic infection. During the second wave of COVID-19, all over India a spurt of increased reporting of Mucoraecea infection was experienced. Compromised individual immunity system was suspected. Its early diagnosis and suitable surgical intervention were essential to decrease morbidity and mortality. Aim of the Study: To study the demography, clinical features, risk factors, laboratory investigations, and radiological findings of patients with mucormycosis and to evaluate the clinical outcomes in each case. Materials: A cross sectional study from the Department of ENT of Government Medical College Hospital, Ongole;350 COVID-19 RT-PCR positive patients presented with clinical symptoms and signs of Mucormycosis between February 2021 and February 2022 were analyzed. All age groups and genders were included. Mucormycosis proved on microscopic examination of the aspirate or histopathologies of tissue specimens were included. Clinical findings, risk factors, comorbidities, outcome of the disease, biochemical and hematological investigations, radiological signs, nature of fungal elements isolated, treatment instituted were noted. Surgical procedures included were Functional Endoscopic sinus surgery, extended Endoscopic sinus surgery, Medial maxillectomy, ethmoidectomy, Sphenoid exploration, frontal sinusotomy, Orbital exenteration and Skull base surgeries. Antifungal treatment consisted of administration of liposomal Amphotericin B and posaconazole. Result(s): 350 patients included in this study;268/350 (76.57%) males and 82/350 (23.42%) females with a male to female ratio of 3.26:1. 211 (60.28%) patients living in rural areas and 139 (39.71%) living in the urban areas. 324 (92.57%) patients were positive for COVID-19 (RT-PCR) test and 26 patients were negative. There were 233 (66.57%) patients who were obese with more than 30 BMI index and 117 (33.42%) who were with less than 30 BMI index. 299 (85.42%) patients were diabetic and 51 (14.57%) patients were non diabetic. Vaccination was taken 188 (53.71%) of the patients and not taken by 162 (46.28%) of the patients. Mortality rate was 09/350 (02.57%). It was observed that the variables such as Living area, COVID-19 (RT-OCR) test positivity, obesity, Diabetes mellitus and usage of steroids were significantly associated with Mucormycosis in this study. Conclusion(s): Mucormycosis was found to be common in males, from the rural areas. Other significant risk factors for Mucormycosis were COVID-19 (RT-OCR) test positivity, obesity, Diabetes mellitus and usage of steroids. The most common clinical symptoms and signs among were nasal obstruction with noisy breathing, blood stained nasal discharge, headache, periorbital swelling, reduced vision, Ptosis, external ophthalmoplegia, and facial pains were common. Surgical management reduced the morbidity and mortality of Mucormycosis in this study.Copyright © 2023, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.
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Background: COVID-19 associated pulmonary aspergillosis (CAPA) complicates the course of critically ill COVID-19 patients. Delay in diagnosis and reports of azole resistance in CAPA patients lead to adverse outcome. We had previously reported CAPA rates of 21.7% from our center with high mortality. To detect azole resistance in Aspergillus species isolated from CAPA patients, we performed azole resistance screening. Material(s) and Method(s): Aspergillus species isolated from tracheal aspirates of CAPA patients admitted in Aga Khan University Hospital, Karachi, Pakistan during July 2020- January 2022, were screened for azole resistance as per CDC protocol. Minimum inhibitory concentration of screening positive strains were determined using YeastOne Sensititre plate. Result(s): 92 Aspergillus isolates were screened from 73 CAPA patients for azole resistance. Only 2 (2.17%) A. flavus isolates showed growth on voriconazole well, while other 90 (97%) isolates were screened negative for resistance (Table. 1). MICs of these two strains against posaconazole, voriconazole and itraconazole were 0.5 ug/mL, 1 ug/mL and 0.25ug/mL respectively. Table. 1: Aspergillus species distribution and growth on azole resistance screen agar Conclusion(s): We also did not find any azole resistance in this study. Periodic surveillance for the emergence of azole-resistant clinical isolates using molecular approaches is essential.
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Background: Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. Case description and systematic review: A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26;19.2%) or bronchoscopic instillation (1/26;3.8%) of amphotericin B and surgery (6/26;23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Conclusion: Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible. © 2022 Wiley-VCH GmbH.
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Coronavirus disease 2019 (COVID-19) is a pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 infections may be associated with a wide range of bacterial and fungal co-infections. Recent studies are reporting invasive fungal infection associated with severe COVID-19. Herein, we report a case of COVID-19 rhino-orbital mucormycosis infection caused by Rhizopus sps in a 32 year old diabetic patient who was successfully managed with early aggressive debridement of infected tissue endoscopically with extended ethmoidectomy by modified Denker's approach along with orbital decompression and antifungal therapy with Liposomal Amphotericin B and Posaconazole. Serial diagnostic nasal endoscopy showed no evidence of progression of the infection. The patient was discharged on 21st day of hospitalization still on oral Posaconazole for a total of 3 months. Copyright © 2022, Kathmandu University. All rights reserved.
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OBJECTIVE: To report six cases of Rhizopus homothallicus rhino-orbital-cerebral mucormycosis in North India between April 2021 and July 2021. CASE DETAILS: All six patients had diabetes, concomitant SARS-CoV-2 infection, a history of oxygen requirement and steroid intake. Among these six cases 4 were female. All patients presented with sinus pain and peri-orbital swelling. COVID-19-associated mucormycosis (CAM) was diagnosed based on microbiological examination of the biopsied tissue, and its staging was determined radiologically by CT and MRI. Three patients were in stage III-C, the others were in stage II-C, II-D and IV-A. A multidisciplinary team treated the patients with extensive surgical debridement of the affected tissue, correction of predisposing comorbidities and administration of an antifungal agents. Patients were followed up for 6 months with routine direct nasal endoscopy to check the sinonasal cavity for any recurrence. All the six patients survived at 6 months of follow-up. CONCLUSION: A timely initiated multidisciplinary team-based approach can reduce the mortality in rhino-orbital-cerebral mucormycosis cases caused by R. homothallicus.
Subject(s)
COVID-19 , Mucormycosis , Humans , Female , Male , Mucormycosis/diagnostic imaging , Mucormycosis/therapy , Tertiary Care Centers , SARS-CoV-2 , Antifungal Agents/therapeutic use , IndiaABSTRACT
As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved "Ex3Lx6L" ("E-L-L") motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this "E-L-L" motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the "E-L-L" motif rendered the protein completely resistant to the drug, establishing its specificity toward this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective toward all major variants of concerns of SARS-CoV-2, including Beta, Kappa, Delta, and Omicron. Together, we show that this conserved essential "E-L-L" motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2.
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Introduction: Mucormycosis is a life-threatening fungal infection caused by fungi belonging to the family Mucorales, and the fungus mainly responsible for infection in humans is Rhizopus oryzae. Recently, several cases of coronavirus disease 2019 (COVID-19)-associated mucormycosis are being reported worldwide. Subjects and Methods: A retrospective observational study was conducted in the emergency department at a tertiary care hospital for 2 months. The primary objectives of this study were to assess the risk factors of post COVID-19 the signs and symptoms, toassess the relationship between steroidal usage and post-COVID-19 mucormycosis evaluating the treatment patterns. Results and Discussion: In the current study, 45 cases were examined. It was found that patients with comorbidities, especially diabetes mellitus, i.e., 80%, have more exposure to post-COVID-19 mucormycosis than any other comorbidity. It is also found that methylprednisolone is the major steroid used, accounting for 43% of the steroids used for the treatment of COVID. The treatment included the usage of lipophilic amphotericin B in 61% of the patients, which is associated with lipophilic posaconazole in 95% of the patients. Conclusion: Post-COVID-19 mucormycosis is a major threat to the individuals affected with COVID-19. The major risk factor is the presence of diabetes mellitus;therefore, proper measures must be undertaken in diabetic patients. Patient develops any symptoms related to the eyes, nose, face, lungs, and skin should seek a medical emergency to avoid chronic complications.
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Mucormycosis is a rare opportunistic fungal infection observed in immunocompromised individuals or in those with uncontrolled diabetes mellitus. During the coronavirus disease 2019 (COVID-19) pandemic, there has been a steep increase in the incidence of mucormycosis among adults. However, the infection is extremely rare in the pediatric population, and its occurrence post-COVID-19 infection has been reported in very few cases. We present a case of cerebral mucormycosis in a 6-year-old immunocompetent girl that was histopathologically confirmed by stereotactic brain biopsy. The fungal infection occurred following asymptomatic COVID-19 infection and this report describes the diagnostic journey and management. It highlights the unusual presentation of cerebral mucormycosis in our case and the role of posaconazole in the successful treatment.
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Background Mucormycosis (MM) is an angioinvasive locally destructive fungal infection. Before the coronavirus disease 2019 (COVID-19) pandemic, it was associated with diabetes (particularly diabetic ketoacidosis), immunosuppressive drugs and trauma. Among its various forms, cerebral invasion is considered to be highly fatal even if with long-term treatment. Treatment with injection amphotericin B (Amph-B) with early surgical interventions is highly efficacious. Liposomal preparation is considered to be superior in the context of fewer side effects. Methods We present a single-centre prospective study of 124 patients with MM in a tertiary care hospital. After the approval from the ethics committee, basic information was taken from all patients including all available past history about the COVID-19 infection and treatment. The studied outcomes were discharge, death and number of days of hospitalisation. Secondary objectives were to estimate the association of MM with known risk factors, to find the association of an outcome with various inflammatory markers, to determine adverse events with the use of injection Amph-B and posaconazole and to find the case fatality rate of MM. Results In our study, we observed that the number of patients with MM was double in the less than 60 years age group. However, mortality was 33.3% in the elderly as compared to 15.29% in patients less than 60 years of age. The majority of the patients (69.35%) were males, but no significant difference in mortality was seen between males and females. The case fatality rate was 20.97%. Ocular symptoms such as orbital swelling and pain were the common presenting symptoms. Almost all patients (93.54%) were diabetics. The non-diabetic group consisted of only 8 (6.4%) patients, and therefore, the comparison was not possible. A total of 20 (16%) out of 124 patients who had received high-dose steroids showed higher mortality (55%). Maximum patients (65.32%) had presented with MM following a past COVID-19 infection. However, a significant number of MM patients (20.96%) had a recent COVID infection and had higher mortality (57.69%) compared to their counterparts. The most common site of involvement in our study was the paranasal sinus (50%) and the outcome was the best in those patients whose disease was localised only to the sinuses, although among 14 (11.29%) patients with cerebral involvement, mortality was maximum (42.85%). Renal impairment and dyselectrolytemia were the most common adverse effects of Amph-B, and 46.42% of patients required surgical removal of the local part. Conclusion We saw that diabetes was a major contributory factor in the etiopathogenesis of MM. COVID-19 could also be a major causative factor by impairing the immune system; however, further studies at the molecular level are required to establish an association. The use of steroid cannot be the only independent risk factor, and other associated factors must be present. Treatment with antifungal and early surgical intervention had good outcomes. Treatment with conventional lyophilized Amph-B was equally efficacious as lipid-based solutions, but with more side effects. Hypokalemia and hypocalcemia were the most common electrolyte abnormalities associated with the use of injection Amph-B. Uncontrolled diabetes, the severity of the COVID-19 infection at presentation, acidosis, a high C-reactive protein level (above 100) and local brain involvement were associated with a poor outcome.
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COVID-19 disease has been associated with fungal infections such as aspergillosis and mucormycosis, especially in diabetic patients who have suffered from a moderately severe form of COVID-19 infection and are treated with steroids. Though there are multiple case reports describing co-infection with mucormycosis during the second wave of the COVID outbreak, the report of a dual fungal infection along with superadded bacterial infection is rare. Here we report a case where the same patient had a fungal storm with aspergillosis and mucormycosis and superadded Klebsiella. She was treated aggressively with antifungal agents, antibiotics, surgical debridement, and other supportive care. She improved and was discharged from the hospital after a long stay. She is being followed up regularly in the outpatient department and doing well.