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In recent times, numerous reports of systemic fungal infections have been a major concern. The angioinvasive fungal infection, mucormycosis has surged in patients with COVID-19 due to various factors, mainly uncontrolled diabetes and inappropriate corticosteroid use. The prevalence of this acute and fatal fungal infection caused by Mucorales-related fungal species has been highest in the Indian population. COVID-associated mucormycosis (CAM) has a propensity for contiguous spread, and exhibits high morbidity as well as mortality. Unless promptly detected and treated, it is associated with a poor prognosis. A high index of suspicion, aggressive surgical debridement and use of systemic antifungal agents continue to be the standard of care for CAM. Moreover, there is an imperative need to address this public health issue by increasing public awareness and education. This article provides a comprehensive overview on the emergence of CAM during the pandemic, the current burden, pathophysiology, diagnostic interventions and management of CAM in Indian clinical practice.
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The article offers medical briefs. Topics include the authorization of a new drug called Gohibic for critically ill patients with COVID-19;the approval of an over-the-counter naloxone nasal spray for opioid overdose treatment;and the Food and Drug Administration approval of a long-acting antifungal called Rezzayo for the treatment of candidemia and invasive candidiasis for hypertension medications.
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Background: With an increase in the spread of the pandemic, ailments related to the COVID illness started to appear. Patients with COVID - 19 infection experienced a worse outcome with an increase in the prevalence of opportunistic infections in the infected person especially Mucormycosis. It was recognized that people with diabetes, cancer, patients undergoing chemotherapy and other immune-compromised conditions can develop Mucormycosis. Systemic steroids and other immune-modulating agents which are the mainstay of treatment for COVID-19 predisposes to the chance of developing invasive fungal infections. Methodology: Here we provide a retrospective analysis in which out of 212 patients who were subjected to screening 13 individuals were KOH mount positive with unique clinical characteristics as well as demographic and therapeutic profile. The information was gathered retrospectively at a single facility that serves a sizable group of patients with varying severity of the Corona virus infection. Results: Of the total in-patients taken into consideration 13 were diagnosed with mucormycosis post COVID-19 infection. The median age was greater among individuals who survived the infections (49.5 years) and those with severe COVID had high chance of dying (23.8), with an overall mortality rate of 64.3 percent. Additionally 61.5 percent of patients had diabetes mellitus and 75% of them died. 11 patients (84.6%) had previously been on steroids for COVID-19. Both the individuals who survived and succumbed to the disease had same level of hyperglycemia. Conclusion: The prevalence of mucormycosis among COVID-19 patients appears to be rising, which may be attributed to increasing usage of steroid, a potential immunocompromised state brought about by the virus per se and the co-morbid conditions. A high index of suspicion and early diagnosis is necessary to bring down the mortality rate This is in addition to the preventive measures and sensible use of immunemodulators. [ FROM AUTHOR] Copyright of Journal of Pharmaceutical Negative Results is the property of ResearchTrentz and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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COVID-19 pandemic has traumatized deep inside in minds and lives of human beings. Those who have survived are at risk of many post-COVID complications; mucormycosis being one of the most common as well as morbid infections. Mucormycosis is also known as black fungus, it is a life-threatening opportunistic fungal infection. Inoculation occurs by inhalation of spores in nose, paranasal air sinuses and in lungs. Mucormycosis is often associated in patients with compromised immunity and it presents with characteristic black necrotic eschar and necrosis. Disease affecting the facial region possess a challenge because it often disseminates with sino-orbital and cranial involvement at the time of diagnosis. Dental practice occasionally encounters unusual and subtle symptoms with non-pathognomonic clinical signs of several fatal diseases which may pretend like a common oral disease. Hence, the key knowledge to oral and primary care physicians and its precise application is necessary for the early diagnosis of such fatal infections to prevent untoward consequences in this COVID era. This article presents a case of mucormycosis with chief complaint of pain and swelling in right front tooth region, which mimicked as periodontal abscess in a patient, leading to delay in the diagnosis possess greater challenges during the treatment.
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Mucormycosis is a rare type of fungal infection commonly known as zygomycosis, the infection tends to crop up more commonly in individuals with low and weakened immunity level, if left untreated, the mucormycosis can be life-threatening and fatal. Mucormycosis previously known as zygomycosis is a consequential type of infection caused by several mildews known as micromycetes. The revised taxonomical studies revealed that the micromycetes causing the infections are classified as the species of phylum Glomeromycota, class Glomeromycetes, subphylum Mucoromycotina, order Mucorales. The genera of Rhizopus, Mucor, Lichtheimia, Cunninghamella, Rhizomucor, and Apophysomyces, constitute the causative agents of the majority of cases of mucormycosis. The angioinvasive type of disorder caused by mucormycosis is further classified as Mucorales. The patients with Diabetes ketoacidosis and diabetes mellitus are at high-risk factors, followed by the patients with organ transplant, immunocompromised disease, and malignancy. The route of exposure to Mucormycosis may be through the wounded infection that can be pneumonic, or dermal in origin. In the ectodermal form, the fungal organism can invade the skin through open or puncture wounds, or the laceration on the skin. However, the infection has a high mortality rate, the key to successful treatment is early diagnosis, and administration of antifungal drugs, with extensive therapy, followed by surgical debridement of the infection. The morbidity and mortality rate are still at a high number, due to the negligence of the patient to seek medical treatment. Hence the early diagnosis and treatment with antifungal drugs with surgical debridement is a must. The efficacy of oral and venous formulations in the treatment of mucorales is still under debate. Despite the aggressive therapy, the mortality rate is increasing worldwide. The studies have to be conducted to invent the fastest treatment protocol for the treatment of Mucormycosis.
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Rhino-orbital mucormycosis (ROM) is an acute and fulminant infection. The number of ROM cases developing after coronavirus disease 2019 (COVID-19) is increasing. A 62-year-old male patient was admitted to the emergency department in northern Syria complaining of new-onset vision loss, swelling, and severe swelling of the left eye. It was noted that a 3-day course of prednisolone 250 mg was given to treat COVID-19. We found that he had a history of diabetes mellitus (DM) for 10 years. Physical examination revealed ptosis, proptosis, and ocular movement restriction in all directions in the left eye. All other systemic examinations were normal. A cranial and orbital magnetic resonance imaging scan performed after hospitalization for further evaluation and treatment showed an increase in the density of the sphenoid, ethmoid, and frontal sinus walls in the left orbit. Despite antifungal and surgical treatment, the patient died on day 14. The use of steroids in treatment and the presence of concomitant DM are the main predisposing factors. The prognosis of this disease, which has a high mortality and morbidity, is adversely affected in geographic regions where health care is inadequate.
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Background: There has been a tremendous increase in number of cases of rhino-orbitocerebral involvement with mucor in the COVID era, as reported from India. It is well established that management of ROCM involves early clinical and radiological diagnosis, reversal of underlying risk factors, prompt antifungal therapy and surgical debridement when indicated. Materials &Methods: Multiplanar MR imaging and CT scan were performed for brain, orbit and paranasal sinuses. All the cases were assessed for involvement of the paranasal sinuses, nasal cavities, orbits and brain. Results: 25 cases with ROCM were identified over 8 months. The mean age of the cases was 56.1 years. 18 of the 25 cases had a positive RT-PCR test result at the time of diagnosis with ROCM. 20 cases had poorly controlled diabetes mellitus, 2 had a hematological malignancy, 2 had chronic kidney disease and 1 had ischemic heart disease. There was involvement of the paranasal sinuses, nasal cavities, orbits and brain inclusing necrosis in most of the cases. The number of cases identified during the interval is much higher than the numbers presenting in the prior 2 years during equivalent intervals than those reported in the literature in different settings in the pre-pandemic era. Conclusions: Rhino-orbito mucormycosis can have aggressive necrosis of the involved paranasal sinuses and orbits with or without cerebral extension. Hence, the correct diagnosis is imperative as prompt antifungal drugs and surgical debridement can significantly reduce mortality and morbidity.
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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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Candida auris, a multidrug-resistant yeast, can cause primary or secondary infections in a wide range of patients, including those diagnosed with the new coronavirus to even healthy individuals. The fungus has been reported in less than a decade on all six continents and in more than 45 countries. Ease of distribution, long shelf life, and resistance to several antifungal drugs have raised concerns about the prevention and management of patients with C. auris infection. Recent reports indicate serious challenges in identifying, understanding the mechanism of drug resistance, and preventing mortality from the infection with this microorganism. Given the prevalence of COVID-19 infection, it is important to identify patients colonized with C. auris correctly and at the early stages, to control and prevent a possible outbreak. In this article, the widespread occurrence of infections due to C. auris in the world and Iran, its clinical manifestations, risk factors, pathogenic mechanisms, diagnostic enhancements and challenges, drug resistance, treatment options, prevention, and control as well as concomitant C. auris infections in patients with COVID-19 virus, are reviewed.
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The disastrous Coronavirus Disease outbreak declared as a global pandemic, has become a potential hazard to public health. The second wave of COVID-19 in India has been strongly linked to the rising cases of various fungal infections including mucormycosis, aspergillosis, candidiasis, and mucor septicus. These fungal infections have been a cause for alarm for the general public. The color-coding of the fungal infections is primarily based on the symptoms observed in the infected patients and not based on the color of the fungi itself. For busting the myths behind fungal infections, a comprehensive and deeper understanding of the facts is needed to overcome this challenge. Rapid diagnosis, reversal of underlying predispositions, surgical excision or debridement, and optimal antifungal therapy are some of the crucial factors in combating these fungal infections. This article provides a comparative review of literature on various fungal infections during COVID-19, that have been threatening worldwide, predominantly in India. A well-established databases literature search was conducted. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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Mucormycosis is a fungal infection which got worsens with time if not diagnosed and treated. The current COVID-19 pandemic has association with fungal infection specifically with mucormycosis. Already immunocompromised patients are easy target for COVID-19 and mucormycosis as well. COVID-19 infection imparts in weak immune system so chances of infection is comparatively high in COVID-19 patients. Furthermore, diabetes, corticosteroid medicines, and a weakened immune system are the most prevalent risk factors for this infection as we discussed in case studies here. The steroid therapy for COVID-19 patients sometimes have negative impact on the patient health and this state encounters many infections including mucormycosis. There are treatments available but less promising and less effective. So, researchers are focusing on the promising agents against mucormycosis. It is reported that early treatment with liposomal amphotericin B (AmB), manogepix, echinocandins isavuconazole, posacanazole and other promising therapeutic agents have overcome the burden of mucormycosis. Lipid formulations of AmB have become the standard treatment for mucormycosis due to their greater safety and efficacy. In this review article, we have discussed case studies with the infection of mucormycosis in COVID-19 patients. Furthermore, we focused on anti-mucormycosis agents with mechanism of action of various therapeutics, including coverage of new antifungal agents being investigated as part of the urgent global response to control and combat this lethal infection, especially those with established risk factors.
Subject(s)
COVID-19 , Mucormycosis , Mycoses , Humans , Pandemics , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Mycoses/drug therapy , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/microbiologyABSTRACT
The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA-EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60-72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2-5), and the simplified acute physiology score (SAPS)-II score was 42 (31-56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10-21.75) after symptoms onset and 9 days (IQR 3-11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis-in the absence of specific invasive investigations, and with a consequent possible increase in mortality-and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians.
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The appointment of antibacterial agents for the treatment of pneumonia that develops with COVID-19 is one of the treatment regimens. Antibacterial agents are prescribed only in the case of the presence of confirmed bacterial co-infec-tion but can be appointed empirically. This approach promotes the development of antibiotic resistance of opportunistic and saprophytic microflora of almost all habitats, including the oropharynx, which can lead to dysbiosis with activation of fungal flora. The aim of the study was to analyze the composition of the oropharyngeal microbiome of patients with viral and bacterial pneumonia who took antibiotics, as well as the sensitivity of fungi of the genus Candida to antifungal drugs for effective treatment of the underlying disease. Methods. The results of the bacteriological examination of 113 patients treated with a diagnosis of COVID-19 were analyzed. Microbiological examination of oropharyngeal swabs was performed by the classical bacteriological method with dosed seeding of suspended material on differential diagnostic media (in particular Sabouraud agar was used for selection of fungi of the genus Candida) and genus identification by morphological, cultural, biochemical properties. Results. PCR tests were performed for all patients in the clinical trial to confirm the diagnosis of viral and bacterial pneumonia. According to the results of the bacteriological examination, fungi of the genus Candida were found in 52 (46.0%) patients with pneumonia associated with COVID-19. The analysis of prescriptions showed that only 14 (26.9%) patients were treated with one antibiotic, two antibiotics were prescribed to 31 (59.6%) patients, and three — to 7 (13.5%). In the structure of antibiotic therapy, the lion’s share were cephalosporins of the third generation (ceftriaxone, hepacef) — 33 (63.5%), and macrolides (azithromycin) — 16 (30.8%) patients. In the structure of the oropharyngeal microbiome, according to the results of the bacteriological research, fungi of the genus Candida significantly prevailed, which were found in 52 (46.0%), and in 29 patients (25.7%) S. pneumonia was found. The sensitivity of fungi of the genus Candida to antifungal agents was analyzed, and the maximum number of resistant strains was detected to nystatin and amphotericin — 38.5% and 26.9%, with only 8 (15.3%) fungi of the genus Candida sensitive to nystatin. Conclusions. All patients with viral-bacterial pneumonia associated with COVID-19 received antibiotic therapy with the lion’s share of third-generation cephalosporins (63.5%) and macrolides (30.8%). According to the results of the bacteriological examination of the oropharyngeal microbiome after antibiotic therapy, fungi of the genus Candida predominated (46.0%), followed by S. pneumoniae (25.7%). Isolated strains of fungi of the genus Candida showed resistance to nystatin (38.5%) and amphotericin (26.9%). Antifungal agents of the imidazole subgroup have shown high efficiency and a low percentage of resistant strains, which allows us to recommend them for the treatment of complications of COVID-19 caused by fungi of the genus Candida. © Publisher PH «Akademperiodyka» of the NAS of Ukraine, 2022. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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Introduction: Aneurysm formation of internal carotid arteries (ICA) in patients with mucormycosis is a scarce phenomenon. However, the prevalence of rhino-cerebral mucormycosis has been reported to increase after the Coronavirus disease 2019 (COVID-19) pandemic. Case Presentation: Three patients with stroke and subarachnoid hemorrhage presented due to ICA aneurysm after the involvement of adjacent paranasal sinuses (PNS) with mucormycosis. They had a history of diabetes and corticosteroid use. Also, one of them was treated with imatinib. Two out of the three patients were infected with SARS-CoV-2 before developing mucormycosis. Two patients had diagnostic angiography before endovascular intervention. One patient did not undergo any therapeutic intervention due to total artery occlusion, whereas the other patient experienced a successful parent artery occlusion by coiling and only survived this patient. Although all patients received antifungal treatment and surgical debridement, two of them died. Conclusions: In patients with rhino-cerebral mucormycosis, aneurysm evolution should be promptly and meticulously investigated by Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA). As this type of aneurysm is very fast-growing, as soon as the involvement of the sphenoid sinus is detected, the possibility of ICA aneurysm formation should always be kept in mind. If the patient develops an aneurysm, prompt intensive antifungal therapy and therapeutic endovascular interventions such as stenting, coiling, or sacrificing should be considered as soon as possible to optimize outcomes.
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The US Centers for Disease Control and Prevention (CDC) said that mucormycosis, also known as black fungus, is a “serious but rare” infection caused by a group of moulds called mucormycetes. According to Raghuraj Hegde, consultant eye surgeon at Manipal Hospital, in Bengaluru, India, the virulence of the new strain of COVID-19 virus causes patients’ blood sugars to shoot up, which in turn provides a suitable environment for mucormycosis. According to Nair, mucormycosis was an extremely rare condition and the availability of amphotericin B was adequate.
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Objectives: To examine the clinical characteristics, drug resistance, and factors influencing development of a pulmonary fungal infection in patients with severe respiratory diseases in order to provide a reference for clinical treatment.
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The objective of this case report is to highlight the impending secondary fungal infection outbreak in COVID-19 and the need to contain this emerging spread of fungal infections. Three case reports are presented, all from India. Altered immunity is an important risk factor for mucormycosis. In addition, diabetes has been noted to be critical for the development of mucormycosis in immunocompetent patients. Candidiasis is an infection caused by the Candida species due to the immunosuppressed state developed by the use of glucocorticoids, which results in secondary fungal infection requiring urgent medical attention.
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Background Excessive use of corticosteroids therapy along with gross immunocompromised conditions in the novel coronavirus disease 2019 (COVID-19) pandemic has raised the risks of contracting opportunistic fungal infections. Here, we describe our experience with the implementation of a surgical protocol to treat and reconstruct rhino-orbital-cerebral mucormycosis. Methods A retrospective review of our prospectively maintained database was conducted on consecutive patients diagnosed with mucormycosis undergoing immediate reconstruction utilizing our "Mucormycosis Management Protocol." All patients included in this study underwent reconstruction after recovering from COVID-19. Wide local excision was performed in all cases removing all suspected and edematous tissue. Reconstruction was done primarily after clear margins were achieved on clinical assessment under a cover of injectable liposomal amphotericin B. Results Fourteen patients were included. The average age was 43.6 years and follow-up was 24.3 days. Thirteen patients had been admitted for inpatient care of COVID-19. Steroid therapy was implemented for 2 weeks in 11 patients and for 3 weeks in 3 patients. Eight patients (57.1%) had a maxillectomy and mucosal lining resection with/without skin excision, and six patients (42.8%) underwent maxillectomy and wide tissue excision (maxillectomy and partial zygomatic resection, orbital exenteration, orbital floor resection, nose debridement, or skull base debridement). Anterolateral thigh (ALT) flaps were used to cover defects in all patients. All flaps survived. No major or minor complications occurred. No recurrence of mucormycosis was noted. Conclusion The approach presented in this study indicates that immediate reconstruction is safe and reliable in cases when appropriate tissue resection is accomplished. Further studies are required to verify the external validity of these findings.
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One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7-12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.