Opportunistic Invasive Fungal Infections Research Articles

Fungal positivity seen in tertiary care hospital during COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) pandemic has been prevailing for more than a year, associated with an increased number of opportunistic invasive fungal infections in patients who have been critically ill or immunocompromised. In this retrospective study, details of various clinical specimens received from suspected patients of fungal infections were studied. Fungal cultures were positive in 64% (51 out of 79) of COVID-19-positive patients and 43% (163 out of 381) of COVID-19-negative patients during the second wave of COVID-19 in 2021. Among COVID-19-infected patients, the most commonly isolated fungi were Candida spp. (63%), followed by Aspergillus spp. (15%) and Mucor spp. (6%). The majority of samples that tested positive in COVID-19-infected patients were urine (17% from COVID-19-positive and 83% from COVID-19-negative patients), followed by serum (tested for Aspergillus galactomannan). Candida isolation was observed in 27% (21/79) of urine samples and 15% (12/79) of respiratory samples [bronchoalveolar lavage (BAL), tracheal aspirate, and sputum] from COVID-19-positive patients. Rhizopus arrhizus and Rhizopus homothallicus were isolated from nasal and tissue samples in 6% of COVID-19-positive patients. There was an overall increase in fungal co-isolations during the COVID-19 pandemic (64% in COVID-19-positive and 43% in COVID-19-negative patients), which is a matter of great concern. The correlation of clinical symptomatology and laboratory isolation is important for the diagnosis and effective management of these patients.

Rapidly Developing and Elusive Rhino-Orbital-Cerebral Mucormycosis

Purpose: To report a case of rapidly progressing rhino-orbital cerebral mucormycosis that was particularly difficult to diagnose, initially presenting as orbital apex syndrome. Major findings: In this case, a 59-year-old male patient with uncontrolled diabetes presented with a history of facial pain with no ocular involvement. Within 1 day of hospitalization, the patient developed complete ophthalmoplegia and total visual impairment of the right eye. Over the course of 2 hospital stays, several biopsies resulted in no significant histopathological findings, and several cultures resulted in growth of only a single colony of rhizopus mucor from the sinonasal mucosa. Given the high clinical suspicion of an invasive fungal infection, a universal PCR test was performed from a rapidly developing abscess in the frontal lobe and confirmed a diagnosis of mucormycosis. Conclusions: Orbital apex syndrome is a significant diagnosis that can be caused by a variety of factors, including those of fungal, bacterial, neoplastic, or inflammatory origin. Fungal infections, are a particularly concerning cause of orbital apex syndrome, given their ability to penetrate in and through the orbit to the brain, often resulting in an alarmingly high mortality rate. Mucormycosis, specifically rhino-orbital cerebral mucormycosis, is a very severe opportunistic invasive fungal infection, most often afflicting the immunocompromised. A clinician must be very thorough in their workup so as to not miss such a devastating diagnosis. Histopathology and cell cultures are currently the gold standard for diagnosis, with the potential to augment their technical success through the use of molecular techniques, such as universal PCR.

SIADH secondary to rhino-orbito-cerebral mucormycosis: A case report.

Invasive fungal mucormycosis and its outcome as SIADH and orbital apex syndrome is uncommon. Mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Early diagnosis and prompt treatment with antifungal, endoscopic surgery, and controlling of diabetes can be beneficial. Mucormycosis is an opportunistic invasive fungal infection which is rare and fatal and can even cause intracranial invasion leading to SIADH. The infrequency with which mucormycosis with SIADH is encountered makes it a formidable diagnostic challenge. 70-year-old women uncontrolled diabetes mellitus presented with bilious vomiting and persistent headache with ptosis, proptosis, absence of extraocular movement, pupillary light reflex, and light perception of left eye. Radiographic investigation, KOH mount, and Biopsy showed mucormycosis in sinus with intracranial extension leading to SIADH. Further investigation revealed hyponatremia, decreased plasma osmolality. Then, when diabetes was controlled and hydrocortisone and amphotericin was given along with Endoscopic sinus debridement, SIADH was well controlled. This case illustrates the potential of mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Prompt diagnosis through clinical history, radiological investigation, and laboratory parameters are important and its treatment is crucial for the better prognosis.

Hematological Indices in COVID-19 Patients with Rhinosinusitis Mucormycosis.

Rhinosinusitis mucormycosis (RM) is an invasive opportunistic fungal infection, especially among COVID-19 patients. The current study aimed to assess the peripheral blood hematological disorders of COVID-19 patients-associated RM. During ten month, in two COVID-19 centers in Mashhad, Iran, from June 2021 to March 2022, eighty-three patients suspected of COVID-19 with rhinosinusitis or rhino-orbital mucormycosis participated in this study. The hematological indices of these patients were measured by independent sample T-test or Mann-Whitney test for quantitative data, and the qualitative variables were analyzed using Chi-square or Fisher's exact test in SPSS version 20 at a significance level of 0.05. Of the COVID-19 patients, 40 (48.2%) were affected by RM, and leukocytosis due to neutrophilia was observed in 30% of them. Leukocyte counts were normal in 10 (25%) patients, but 1 (2.5%) and 3 (7.5%) had leukopenia and lymphopenia, respectively. Leukocytosis plus lymphopenia was observed in 7 (17.5%) patients. Also, the synchronicity of leukopenia and lymphopenia was seen in 5 (12.5%) patients. Leukopenia, lymphopenia, and neutropenia have occurred concurrently in 2 (5%) patients. The complete blood count (CBC) showed that RBCs, hemoglobin (Hb), hematocrit (HCT), MCH, MCHC, platelet (PLT), and lymphocytes decreased while neutrophils increased. Among the hematological parameters, leukocytosis due to neutrophilia and reduction in Hb, HCT, and PLT are more dominant factors in COVID-19 patients-associated RM.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study

Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

SAT058 Diabetes Complicated By DKA, Mucormycosis And Covid-19

Abstract Disclosure: A. Gordon: None. Background: Mucormycosis is an invasive opportunistic fungal infection, that although rare, has an estimated all-cause mortality of 54%. Even with aggressive treatment, significant tissue necrosis and bone destruction can occur. Risk factors include diabetes, acidosis (as in diabetic ketoacidosis), excess iron, transplant, malignancy, kidney and liver disease, immunosuppressant and corticosteroid use - and in more recent times, the Covid-19 infection. We present a case of invasive rhino-orbital cerebral mucormycosis in the setting of DKA, uncontrolled diabetes and Covid-19. Case: A 60-year-old female with history of uncontrolled type 2 diabetes (HbA1c 14.3%) presented after being found unresponsive. Her exam was significant for encephalopathy, complete left eye ophthalmoplegia and right-sided hemiparesis. She was hemodynamically stable without fever. Initial labs showed significant hyperglycemia with an elevated anion gap and beta-hydroxybutyrate indicative of diabetic ketoacidosis (DKA). She had a lumbar puncture which showed leukocytosis with neutrophilia (146 WBC, 39% neutrophils), elevated glucose and normal protein; CSF culture was negative for growth. She also tested positive for Covid-19 although CXR was unremarkable and she did not require treatment. Initial CT/CTA head/neck showed complete occlusion of the left cervical internal carotid artery with associated acute/subacute infarcts in the left frontal, parietal, temporal and occipital lobes. CT sinuses showed severe frontal, maxillary and ethmoid sinus mucosal wall thickening with left premaxillary soft tissue swelling and leftward nasal septum deviation. Finally, orbital imaging showed left cavernous sinus thrombosis, left superior ophthalmic vein thrombosis, and necrosis vs devascularization of the extraocular muscles. She was initially treated with fluids, an insulin infusion and broad-spectrum antibiotics and was evaluated by neurology, ophthalmology, infectious disease and otolaryngology. She underwent surgical debridement with left maxillary antrostomy, left total ethmoidectomies and septoplasty. Sinus cultures were positive for MSSA (methicillin sensitive staph aureus) and tissue pathology showed angioinvasive fungal disease compatible with Mucor/Rhizomucor species. Antimicrobial coverage was changed to intravenous Nafcillin and Amphotericin B, and she underwent further surgical debridement twice more. Repeat brain imaging to evaluate for disease progression is pending. Discussion: Early detection and aggressive treatment of Mucormycosis with surgical debridement and Amphotericin B can improve patient outcomes, however the mortality rate is still significant. Therefore, tight glycemic control in high risk groups is imperative, particularly in those with uncontrolled diabetes complicated by DKA and Covid-19 infection (with or without steroid treatment). Presentation: Saturday, June 17, 2023

Glycemic Control Variations In Covid-19 Associated Mucormycosis”

Background: Mucormycosis is opportunistic invasive fungal infection characterised by angioivasion, thrombosis and necrosis of the tissues. Diabetes mellitus being the commonest immunocompromised state predisposing to mucormycosis in India, a study about glycemic control in CAM (covid-19 associated mucormycosis) patients and the severity of mucormycosis was necessary so as to reduce the morbidity and mortality in CAM patients. Methods: A retrospective descriptive study was conducted between May 2021 and July 2021 at Bowring &amp; Lady Curzon hospital. 315 patients with post-covid ROCM (rhino-orbito-cerebral mucormycosis) were included in the study. Glycemic control of the patients was monitored with FBS, PPBS, HBA1C values.The extent and severity of CAM was studied in patients with good and poor glycemic control.. Results: 243 (77.14%) patients were male and 72 (22.86%) were female. 296 (93.97% )patients had prior history of diabetes mellitus and 19 (6.03%) patients had newly detected diabetes mellitus. 275(87.30%) patients had poor glycemic control. 17 (6.18%) patients out of 275 presented with diabetic ketoacidosis (DKA). 40 (12.70%) patients had good glycemic control. Conclusions: Diabetes mellitus has emerged as important risk factor associated with development of mucormycosis. In covid-19, poorly controlled diabetes, steroid induced hyperglycemia, covid induced insulin resistance act as fertile land for the development of mucormycosis. Hence monitoring glycemic status, judicious use of steroids, control of sugars may help in reducing the severity or occurance of mucormycosis. Keywords: Mucormycosis, Diabetes mellitus, Covid-19 associated mucormycosis, Hyperglycemia.

P163 Successful management of COVID-19-associated mucormycosis in state of pernambuco, northestearn brazil: 2 case reports

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesDuring the COVID-19 pandemic, several cases of mucormycosis related to SARS-CoV-2 were reported. This association is still poorly studied due to its recent emergence and makes diagnosis and treatment challenging. Usually, patients who are affected by this infection are immunocompromised by corticosteroid treatment and uncontrolled diabetes mellitus, being mucormycosis a life-threatening opportunistic invasive fungal infection caused by mucoromycetes, which reaches a mortality rate of about 50%, even with treatment. Thus, this association requires as much information as possible about the pathogenesis and treatment.MethodsHere, we report two cases with conclusive diagnosis and positive evolution to mucormycosis associated with COVID-19 after corticosteroid therapy.ResultsThe first case was a 68-year-old woman, hypertensive and diabetic, who was affected by SARS-CoV-2, with intense ocular pain and paralysis of extrinsic ocular muscles of the right eye and eyelid. The patient underwent CT scan of the sinuses with contrast, which showed signs on maxillary. The patient was submitted to sinusectomy with orbital decompression and the material from the surgery was sent for fungal investigation, which 20% KOH direct exam showed hyaline, sparsely-septate, broad, ribbon-like hyphae with irregular right-angle branching. Rhizopus oryzae was isolated on Sabouraud agar. Mucormycosis was diagnosed in the facial sinuses, and resolution of infection was obtained with liposomal amphotericin B. The second case was a 59-year-old woman, obesity degree 3, asthmatic and history of COVID-19, with history of abscesses in oral mucosa and palate, with drainage of brown secretion after 30 days of COVID-19 resolution. After medical discharge, the patient was evaluated by an oral and maxillofacial surgeon to solve an esthetic problem, when the material was collected for biopsy of the mucosal lesions. Histopathological exam showed aseptic thick mycelial filaments presenting right angle bifurcation, suggestive of Mucorales (mucormycosis). The patient was readmitted to the hospital for mucormycosis treatment based on isavuconazole (200 mg, q8 as attack dose on Day 1 and 2, and 3 toward q24), and treatment evolved positively with no need for surgical intervention. We conclude that the extensive use of steroids associated with diabetes is the main factor for the appearance of mucormycosis after COVID-19, but with a conclusive diagnosis and correct treatment, this infection can have a good evolution, resulting in an improvement in the patient's clinical condition, reducing the risk of death for this infection.ConclusionIsavuconazole appears to be a drug with a safe profile and with curative potential for mucormycosis. The possibility of oral use from the third day at its maintenance dose (200 mg/day) with intravenous use in the first 48 h at a dose of 200 mg every 8 h. Diabetic patients are more prone to infection, but patients infected with SARS CoV 2 using corticosteroids have shown to be a risk group for this fungus.

Diagnosis and management of mucormycosis in the dental clinic: A guide for oral health professionals in India.

With the current pandemic raging over the world, science and medicine is faced with hereto with unfought enemies or less fought opponent in the form of viruses and consequently, other biotic entities. While researchers are striving to identify and conquer the variants of COVID-19, other innocuous organisms are raising their ugly heads in the form of opportunistic fungal infections. Mucormycosis/Black Fungus is an invasive opportunistic fungal infection caused by mucorale species. It spreads through blood vessels causing thrombosis, ischemia, and necrosis. Population with pre-existing immunocompromised conditions such as Diabetes Mellitus, Malignancy, Long-term immunosuppressant therapy are more susceptible. Mucormycosis associated with Corona Virus Disease-2019 (COVID-19) proved to be catastrophic due to its high mortality rates. Rhino orbital Mucormycosis is the most common form. The primary care physician, being the first and often, (more so in developing countries) and being the only point of contact with a healthcare professional, plays a pivotal role in the diagnosis and management of this condition. The keystone to decreasing mortality is early detection and diagnosis followed by preventive measures to control progression to the brain. A multidisciplinary approach by various specialties is a prerequisite for effective diagnosis and management. Antifungal therapy, surgical debridement, and resection of the affected areas are protocols to be followed. Post-operative defects cause impairment of function, phonetics, and esthetics. Prosthetic rehabilitation of these defects has shown favorable results, especially in the aged and immunocompromised individuals.

COVID-Associated Mucormycosis: Review of Cases Reported Worldwide and in India

Objective: The aim of this review literature is to collate and analyse various case reports and series reporting mucormycosis in COVID and post-COVID patients in India and worldwide. Methods: A systematic literature search was conducted from December 2019 to June 2021 using keywords. Details of all the case reports/ series that reported rhino-orbital-cerebral mucormycosis in COVID and post-COVID settings were retrieved and analysed. Results: In this systematic review, 33 articles were included and a total of 181 cases of mucormycosis in COVID and post-COVID patients were reported. Mucormycosis was predominantly seen in males (71.2%) as compared to females (28.7%). History of steroid use was present in 113 patients (62.4%). Type 2 diabetes mellitus was the most common independent risk factor, present in 138 patients (76%). Sino-nasal involvement was seen in 27 patients (14.9%), rhino-orbital involvement in 114 patients (62.9%), andrhino-orbital-cerebral involvement was observed in 40 patients (22%). Improvement in clinical status was observed in 106 patients (58.5%) while 38 patients (21%) expired. Conclusions: A rapid rise in cases of mucormycosis had been reported in the COVID era. Unwarranted use of steroids coupled with uncontrolled hyperglycemia, unregulated activation of inflammatory mediators and overactivation of entry-point receptors inflicted by the Coronavirus cause a state of immune dysregulation, leading to opportunistic invasive fungal infections. A delay in diagnosis can result in disfigurement, functional loss, or even death. Multidisciplinary management with prompt reversal of risk factors is recommended.

Predisposing Factors of Mycotic Infections in Covid-19 Patients

The coronavirus disease 2019 pandemic (COVID-19) has led to considerable hike in hospitalizations for pneumonia with multiorgan disease requiring immediate hospital care, maintenance of oxygen saturation level, and severe cases requiring mechanical ventilation. This opens the window of opportunity to microscopic organisms such as different species of fungus including Candida, Aspergillus, Rhizopus, and Cryptococcus adding other fungi causing opportunistic invasive fungal infections (OIFIs), and other bacteria to cause concurrent infections in COVID-19-diseased patients which on occasion not promptly diagnosed and are mostly diagnosed after death, which get chance due to invasive procedures such as intubation and immunosuppressant drugs which mostly consists of corticosteroids, patient with diabetes mellitus or any other chronic disease causing immunosuppression, patient having a history of chronic obstructive airway disease, development of antibiotic resistance, and vulnerability of pulmonary tissues regarding developing colony for mycotic infections. In this review, we talk over the character of mycotic concurrent infections in aggravation of COVID-19 disease severity and focus on arising trends associated with fungal infections in coronavirus-diseased (COVID-19 diseased) cases. In addition, this review impart the view on the risky component for concurrent mycotic infections in COVID-19 diseased patients who are hospitalized and focuses the possible task of extended immunemodulatory treatments in managing concurrent mycotic infections, comprising COVID-19-associated pulmonary aspergillosis, COVID-19-associated Candidiasis, and mucormycosis. This article restates the demand for prompt detection regarding presumed COVID-19-related systematic mycosis in the health-care settings which could empower fast OIFI diagnosis, treatment, and lowers the mortality rate.

Disseminated Cryptococcosis Complicating Severe SARS-CoV-2 Infection

Opportunistic invasive fungal infections (IFI) have been described in severe SARS-CoV-2 infection. COVID-19-related cytokine storm, immune dysregulation and lymphopenia may increase IFI susceptibility in comorbid patients. We described the case of a 64-year-old man with respiratory failure due to SARS-CoV-2 infection complicated with disseminated cryptococosis. We analyzed the role played by the SARS-CoV-2-associated lymphopenia and the cumulative risk factors that lead to secondary infection by Cryptococcus neoformans, and its part in the dysregulation of the immunity response.

Rhino-Cerebral Mucormycosis with Otologic Involvement.

Mucormycosis is an opportunistic invasive fungal infection, recently been detected in Covid-19 due to several underlying conditions. Otologic involvement in such patients though exceptional, should not be simply ignored even when presented without any clinical signs or symptoms. This report manifests the need of evaluating otologic involvement in post-covid mucormycosis.

Coronavirus Disease 2019-Associated Invasive Fungal Infection.

Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19–associated fungal infections.

GET THE MUNKII OFF YOUR BACK! A RARE BLACK MOLD CAPRONIA MUNKII CAUSING INVASIVE FUNGAL INFECTION IN AN IMMUNOCOMPROMISED INDIVIDUAL

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Individuals receiving chemotherapy or undergoing transplantation are increasingly susceptible to invasive fungal infections. They are commonly caused by opportunistic pathogens like Aspergillus and Candida and are associated with high morbidity and mortality. Such individuals are also susceptible to invasive mold infections. We present a rare case of a black mold Capronia munkii causing cavitary lung lesions in a patient with NHL. CASE PRESENTATION: A 65-year-old female with non-Hodgkin's Lymphoma, CNS lymphoma treated with chemotherapy and autologous stem cell transplant five years ago, had progression of disease last year. She began Ibrutinib therapy for her lymphoma. She was admitted to the hospital for altered mental status due to progression of CNS disease. She developed worsening respiratory failure during hospitalization requiring intubation and mechanical ventilation. She was empirically treated with intravenous vancomycin and piperacillin-tazobactam. Her initial infectious workup and lumbar puncture was negative. Computed tomography (CT) of her chest showed new diffuse ground glass opacities.Bronchial wash was notable for black mold Capronia munkii. She was started on Voriconazole and Amphotericin B. Repeat CT chest showed improving opacities with increasing apical cystic lesions. Respiratory failure can be attributed to mold infection in the lung, immunotherapy-induced pneumonitis and organizing pneumonia. After multiple failed spontaneous breathing trials and septic shock necessitating vasopressors, she was transitioned to comfort care and subsequently expired. DISCUSSION: Capronia munkii is a saprotrophic yeast commonly found on decaying plant matter. There is a lack of clinical information on this mold in literature. It is closely related phylogenetically to Exophiala dermatides which is a neurotrophic black mold. It typically causes a non-specific granulomatous inflammatory response. The host responses are highly variable, and include pulmonary cyst formation and tissue necrosis. The patient's immunosuppression and cystic lesions on CT scan make invasive black mold infection likely. Biopsy of the cavitary lesions to determine the presence of mold would have been confirmatory. The lack of response to anti-fungal treatment reiterates the high mortality associated with this rare infection. CONCLUSIONS: Invasive fungal infections have become more prevalent due to increasing number of individuals undergoing transplantation or receiving aggressive immunosuppression and chemotherapy. Early diagnosis and prompt treatment of uncommon pathogens like black mold with appropriate azole and caspofungin antibiotics is essential to prevent poor outcomes. Newer molecular techniques such as 18S ribosomal RNA PCR and genome sequencing have led to improved diagnosis.Treatment algorithms should be adapted to accommodate changing epidemiologies and anti-fungal drug resistance patterns. REFERENCE #1: Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i39-i47. doi: 10.1093/jac/dkx032. PMID: 28355466. REFERENCE #2: Enoch DA, Yang H, Aliyu SH, Micallef C. The Changing Epidemiology of Invasive Fungal Infections. Methods Mol Biol. 2017;1508:17-65. doi: 10.1007/978-1-4939-6515-1_2. PMID: 27837497. REFERENCE #3: Badiee P, Hashemizadeh Z. Opportunistic invasive fungal infections: diagnosis & clinical management. Indian J Med Res. 2014 Feb;139(2):195-204. PMID: 24718393; PMCID: PMC4001330. DISCLOSURES: No relevant relationships by Padmastuti Akella, source=Web Response No relevant relationships by Saira Imran, source=Web Response No relevant relationships by Shashank Nuguru, source=Web Response

Predisposing factors of important invasive fungal coinfections in COVID-19 patients: a review article.

Severe acute respiratory syndrome coronavirus-2 has caused a devastating pandemic lasting for more than a year. To date, 47 million individuals have been infected and 1.2 million individuals have died worldwide. Some of the most important coinfections in patients with coronavirus disease 2019 (COVID-19) are opportunistic invasive fungal infections (OIFIs), which are sometimes not rapidly diagnosed and are often diagnosed after death. Aspergillosis and candidiasis are the most prevalent OIFIs in patients with COVID-19. Mycormycosis, cryptococcosis, and other fungal diseases have also been documented more rarely. This review aimed to summarize factors affecting COVID-19 transmission, prevalence, morbidity, and mortality in Iran as well as to review common OIFIs in patients with COVID-19. Immunological factors, underlying diseases, and social, cultural, and environmental factors can affect COVID-19 transmission. There is a need to improve diagnostic and therapeutic criteria for OIFIs and to optimize management procedures so that patients with OIFIs can receive treatment as rapidly as possible. Screening of patients with confirmed COVID-19 for OIFIs at the treating physician’s discretion could enable early OIFI diagnosis, treatment, and mortality reduction.

Invasive Opportunistic Fungal Infections and Dermatophytes: Research and Reviews in Clinical Microbiology-A Book Review

Clinical microbiology deals with microorganisms and their interactions with humans. Among the various microbial species present in the environment, fungi are considered as versatile. Numerous fungal species live freely in the air, water, and soil, some cause infections in plants and a few are responsible for opportunistic and invasive infections in humans and animals. This book consists of five chapters that emphasize the role of fungi in human infections, their diagnosis, and prevention.

A case of COVID-19 triggered Rhino-Orbital Pulmonary Mucormycosis in Central India

Mucormycosis is a rare but fatal, invasive opportunistic fungal infection generally described among immunocompromised individuals. The ongoing pandemic coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 has severely compromised the immune system of patients thereby making them vulnerable to mucormycosis, especially when they are lined up with associated comorbidities. Here, we present a case of one such 64-year-old male patient being on corticosteroids and a case of long-standing diabetes mellitus and chronic kidney disease. COVID-19 triggered the mucormycosis in this patient thereby leading to a condition we have described as rhino-orbital pulmonary mucormycosis.

Opportunistic Invasive Fungal Infections Mimicking Progression of Non–Small-Cell Lung Cancer

BackgroundMany studies have shown that invasive pulmonary aspergillosis, cryptococcosis, and mucormycosis can mimic radiographic and clinical features of primary lung cancer. However, more research surveying the incidence and outcomes of these fungal infections among patients with a history of lung cancer is needed. The aim of this study was to describe the occurrence and clinical outcomes of opportunistic invasive fungal infections that can mimic tumors in non–small-cell lung cancer patients. Patients and MethodsPatients seen at Stanford University Medical Center from January 1, 2007, to May 1, 2020, with pulmonary aspergillosis, cryptococcosis, or mucormycosis after non–small-cell lung cancer (NSCLC) diagnosis were reviewed. The European Organization for Research and Treatment of Cancer National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria was used to classify patients with evidence of proven or probable invasive fungal infection within our cohort. ResultsA total of 12 patients with proven or probable invasive mold infection (including 8 cases of aspergillosis) and 1 patient with proven cryptococcosis were identified, without any cases of mucormycosis. Of this cohort, 6 patients (46%) showed radiographic findings that were found to be most consistent with lung cancer by radiologists. Eight cases (62%) were suspected of cancer recurrence or progression by the treatment team on the basis of additional considerations of medical history and clinical symptoms. Most patients had active NSCLC or had a history of recurrence without active NSCLC at the time of fungal discovery (11 patients; 85%). Most patients died without full recovery (7 patients; 54%). ConclusionsInvasive pulmonary aspergillosis and cryptococcosis can often be mistaken as cancer recurrence or progression in patients with a history of NSCLC because of mimicking radiographic and clinical characteristics.

Molecular simulations of fluconazole-mediated inhibition of sterol biosynthesis

Invasive opportunistic fungal infections and antifungal drug resistance prompt the investigation of the underlying molecular mechanisms of the inhibition of the triazole drugs. The target of triazoles is the product of the ERG11 gene, the cytochrome P450 sterol 14α-demethylase (CYP51), which is part of the ergosterol biosynthetic pathway. In this study, molecular dynamics (MD) simulations were performed to reveal the mechanisms of fluconazole inhibitory activities in orthologs of CYP51 present in humans (Hs), and in Mycobacterium tuberculosis (Mt), Candida albicans (Ca) and Candida glabrata (Cg). The conformational diversity of the BC loop in the CYP51-Hs and CYP51-Mt structures alter the catalytic site of these enzymes when compared to the fungal CYPs, resulting in greater conformational variability of the inhibitor. Overall interaction energies are consistent with the observed affinities, but are the result of the competitive interactions of the ligand with the protein residues, the HEME group and water molecules. Specifically, protein–fluconazole interactions are more effective in CYP51-Mt due to polar interactions with the Arg96 residue. These interactions are, however, substituted in fungal enzymes by ligand–HEME interactions, which compensate for the loss of the polar bond and result in a more energetically favored binding. Therefore, the development of ligand with increased specificity to fungal enzymes should focus on the strengthening polar ligand–HEME interactions, while larger hydrophobic ligands are probably best suited to target mycobacterial and human enzymes. These differences and other ligand-binding site-specific interactions are presented and can inspire the design of new inhibitors with greater ortholog specificity.