The mucormycosis and stroke: The learning curve during the second COVID-19 pandemic.

BACKGROUND: The Angio-invasive Rhino-orbito-cerebral mucormycosis (ROCM) producing strokes is a less explored entity. Our hospital, a stroke-ready one, had an opportunity to manage mucormycosis when it was identified as the nodal center for mucormycosis management. We are sharing our experiences and mistakes in managing the cerebrovascular manifestations of ROCM. METHODS: We conducted a prospective observational study during the second wave of the COVID-19 pandemic from 1st May 2021 to 30th September 2021, where consecutive patients aged more than 18 years with microbiologically confirmed cases of ROCM were included. Clinical details (timing of stroke onset after ROCM symptoms, GCS, NIHSS), imaging findings (ASPECTS, the territory of stroke, the pattern of infarct, hemorrhagic transformation, cavernous sinus thrombosis), angiogram findings, management details (IV thrombolysis), and outcomes (mRS at discharge and duration of hospital stay) were documented. We also compared the demographics, clinical features (NIHSS), radiological findings, treatment details, duration of hospital stay, and functional outcome at the discharge of the ROCM stroke patients with stroke patients without ROCM. RESULTS: Stroke developed in 42% of patients with ROCM, predominantly anterior circulation border zone ischemic infarcts. Strokes occurred after a median of five days from the onset of ROCM symptoms. The most common vessel involved was the ophthalmic artery, followed by the cavernous ICA. We could not thrombolyse ROCM stroke patients. ROCM patients who developed stroke compared with patients without stroke had a more infiltrative fungal infection and higher inflammatory markers. Mucormycosis associated stroke patients had higher in-hospital mortality and poor functional outcomes. T CONCLUSION: Due to delayed recognition of stroke symptoms, none received reperfusion strategies, leading to poor functional outcomes. For early stroke detection, ROCM cases need frequent monitoring and education of patients and their relatives about the ALS acronym (loss of ambulation, limb weakness, and loss of speech).

No evidence of resistance to itraconazole in a prospective real-world trial of dermatomycosis in India.

BACKGROUND: The prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India. METHODS: In this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18-60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days. RESULTS: The study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2-10). Clinical response of "healed" or "markedly improved" based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015-0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response. CONCLUSION: COVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India. TRIAL REGISTRATION: Trial registration number: Clinicaltrials.gov NCT03923010.

Risk Factors for Candidemia in Intensive Care Unit: A Matched Case Control Study from North-Western India.

Candidemia is one of the significant causes of mortality amongst critically ill patients in Intensive Care Units (ICUs). This study aimed to assess the incidence, risk factors and antifungal susceptibility pattern in candidemia cases admitted in ICU in a tertiary care hospital in Jaipur, Rajasthan from June 2021 to November 2021. Candida species isolated from blood culture of clinically suspected patients of sepsis were defined as candidemia cases. Blood culture and antifungal susceptibility testing were performed as per standard laboratory protocol. Analyses of risk factors was done between candidemia cases and matched controls in a ratio of 1 : 3. Forty-six candidemic cases and 150 matched controls were included in the study. C. tropicalis was the most prevalent species (22/46; 48%) followed by C. auris (8/46; 17%) and C. albicans (7/46; 15%). Candida species showed good sensitivity to echinocandins (97%) followed by amphotericin B (87%) and voriconazole (80%). In multivariate analysis, longer stay in ICU, presence of an indwelling device, use of immunosuppressive drugs and positive SARS-CoV-2 infection were associated with increased risk of candidemia. The constant evaluation of risk factors is required as prediction of risks associated with candidemia may help to guide targeted preventive measures with reduced morbidity and mortality.

Prevention of acquired invasive fungal infection with decontamination regimen in mechanically ventilated ICU patients: a pre/post observational study.

BACKGROUND: Invasive fungal infections acquired in the intensive care unit (AFI) are life-threating complications of critical illness. However, there is no consensus on antifungal prophylaxis in this setting. Multiple site decontamination is a well-studied prophylaxis against bacterial and fungal infections. Data on the effect of decontamination regimens on AFI are lacking. We hypothesised that multiple site decontamination could decrease the rate of AFI in mechanically ventilated patients. METHODS: We conducted a pre/post observational study in 2 ICUs, on adult patients who required mechanical ventilation for >24 h. During the study period, multiple-site decontamination was added to standard of care. It consists of amphotericin B four times daily in the oropharynx and the gastric tube along with topical antibiotics, chlorhexidine body wash and nasal mupirocin. RESULTS: In 870 patients, there were 27 AFI in 26 patients. Aspergillosis accounted for 20/143 of ventilator-associated pneumonia and candidemia for 7/75 of ICU-acquired bloodstream infections. There were 3/308 (1%) patients with AFI in the decontamination group and 23/562 (4%) in the standard-care group (p = 0.011). In a propensity-score matched analysis, there were 3/308 (1%) and 16/308 (5%) AFI in the decontamination group and the standard-care group respectively (p = 0.004) (3/308 vs 11/308 ventilator-associated pulmonary aspergillosis, respectively [p = 0.055] and 0/308 vs 6/308 candidemia, respectively [p = 0.037]). CONCLUSION: Acquired fungal infection is a rare event, but accounts for a large proportion of ICU-acquired infections. Our study showed a preventive effect of decontamination against acquired fungal infection, especially candidemia.Take home messageAcquired fungal infection (AFI) incidence is close to 4% in mechanically ventilated patients without antifungal prophylaxis (3% for pulmonary aspergillosis and 1% for candidemia).Aspergillosis accounts for 14% of ventilator-associated pneumonia and candidemia for 9% of acquired bloodstream infections.Immunocompromised patients, those infected with SARS-COV 2 or influenza virus, males and patients admitted during the fall season are at higher risk of AFI.Mechanically ventilated patients receiving multiple site decontamination (MSD) have a lower risk of AFI.

Antimicrobial Compounds from Skin Secretions of Species That Belong to the Bufonidae Family.

Skin secretions of toads are a complex mixture of molecules. The substances secreted comprise more than 80 different compounds that show diverse pharmacological activities. The compounds secreted through skin pores and parotid glands are of particular interest because they help toads to endure in habitats full of pathogenic microbes, i.e., bacteria, fungi, viruses, and protozoa, due to their content of components such as bufadienolides, alkaloids, and antimicrobial peptides. We carried out an extensive literature review of relevant articles published until November 2022 in ACS Publications, Google Scholar, PubMed, and ScienceDirect. It was centered on research addressing the biological characterization of the compounds identified in the species of genera Atelopus, Bufo, Duttaphrynus, Melanophryniscus, Peltopryne, Phrynoidis, Rhaebo, and Rhinella, with antibacterial, antifungal, antiviral, and antiparasitic activities; as well as studies performed with analogous compounds and skin secretions of toads that also showed these activities. This review shows that the compounds in the secretions of toads could be candidates for new drugs to treat infectious diseases or be used to develop new molecules with better properties from existing ones. Some compounds in this review showed activity against microorganisms of medical interest such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Coronavirus varieties, HIV, Trypanosoma cruzi, Leishmania chagasi, Plasmodium falciparum, and against different kinds of fungi that affect plants of economic interest.

Rhizopus homothallicus rhino-orbital-cerebral mucormycosis: Six cases from a tertiary care Centre, North India.

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.

Colonized patients by Candida auris: Third and largest outbreak in Brazil and impact of biofilm formation.

Objective: To describe the clinical-epidemiological features of patients colonized by Candida auris in the largest outbreak in Brazil and to show the biofilm formation capacity of yeast strains. Methods: Clinical yeasts suspected of C. auris isolated from urine and surveillance samples were seeded on chromogenic media at 30°C and Sabouraud agar at 42°C. matrix-assisted laser desorption/ionization-time of flight mass spectometry was used for reliable identification. After proteomic confirmation, the genomic approach and culture on Chromagar Candida Plus media were carried out. Biofilm formation was investigated based on metabolic activity, and the clinical-epidemiological profile of patients was described. Results: A total of 11 C. auris clinical yeasts from nine patients were identified between the end of December 2021 and March 2022. Two clinical yeasts were isolates from urine and nine clinical yeasts were isolates from axillary and inguinal surveillance swabs. No case is related to previous Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, all the yeasts showed a high ability of biofilm formation. Conclusion: C. auris requires great vigilance as its high capacity to colonize and form biofilms contributes to its dissemination. The rapid and precise identification of this species is essential for the management, control, and prevention of infections.

An Unusual Case of Severe Pneumonia Caused Due Candida Tropicalis With a Favorable Clinical Response to Antifungals in a Nonimmunocompromised Patient From the Community.

Severe pneumonia due to Candida tropicalis infection mainly occurs in immunosuppressed patients or those currently receiving broad-spectrum antibiotics. Herein, we report a case of severe pneumonia caused due to C tropicalis in an elderly patient. A 72-year-old man with a previous history of hypertension, ischemic stroke, and facial paralysis sequelae treated with the botulinic toxin, was admitted to the hospital for dyspnea. Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection was negative. Computed tomography of the chest revealed bilateral consolidation with left predominance. A bronchoalveolar lavage sample was sent to molecular biology, but no microorganisms were detected using a FilmArray respiratory panel. However, mamanocandidas test for candida was 166 pg/mL (positive), and fungal structures were identified by the MALDI-TOF Biotyper mass spectrometry and attributed to C tropicalis. Antifungal therapy was started using caspofungin 75 mg as the initial dose followed by 50 mg daily. After 10 days of treatment, ventilatory weaning was achieved. By day 14, the patient was decannulated from the tracheostomy. Oral antifungal treatment with voriconazole was continued, and he was discharged from intensive care in good clinical condition. Severe pneumonia due to C tropicalis might occur in specific cases, especially in those patients with risk factors, and must thus be considered when approaching such cases.

Long-term outcomes of transcutaneous retrobulbar amphotericin B in COVID-19-associated mucormycosis.

Purpose: To describe the long-term outcomes of transcutaneous retrobulbar amphotericin B (TRAMB) in COVID-19-associated mucormycosis. Methods: In total, 18 cases of COVID-19-associated mucormycosis were reviewed. In addition to the recommended treatment protocol, all patients were to be given 3.5 mg/ml/day of TRAMB for five days. Results: Of the 18 patients, 2 presented with stage 3a disease, 13 had stage 3c disease, and 3 patients had central nervous system (CNS) involvement (stage 4a and 4c). In addition to planned retrobulbar doses, five patients were given more while two patients received fewer injections (i.e., <5). At the last mean follow-up of 34.67 (±8.88) weeks, 11 patients were in radiological regression and 4 had stable disease while 2 patients had to undergo exenteration; one mortality was observed because of disease progression. Clinical regression in terms of visual and ptosis improvement was seen in seven and nine patients, respectively. Conclusion: Rhino-orbito-cerebral mucormycosis is a serious condition which warrants an aggressive treatment strategy. In unprecedented situations witnessed recently, TRAMB turned out to be an effective and economical alternative. Though large randomized studies are needed to establish its efficacy, TRAMB still manages to halt progression and salvage the globe in significant number of patients, and hence its use should be encouraged on a case-to-case basis especially in developing countries with limited resources.

Serine/Threonine Phosphatase Calcineurin Orchestrates the Intrinsic Resistance to Micafungin in the Human-Pathogenic Fungus Mucor circinelloides.

Procedures such as solid-organ transplants and cancer treatments can leave many patients in an immunocompromised state. This leads to their increased susceptibility to opportunistic diseases such as fungal infections. Mucormycosis infections are continually emerging and pose a serious threat to immunocompromised patients. Recently there has been a sharp increase in mucormycosis cases as a secondary infection in patients battling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Mucorales fungi are notorious for presenting resistance to most antifungal drugs. The absence of effective means to treat these infections results in mortality rates approaching 100% in cases of disseminated infection. One of the most effective antifungal drug classes currently available is the echinocandins. Echinocandins seem to be efficacious in the treatment of many other fungal infections. Unfortunately, susceptibility testing has found that echinocandins have little to no effect on Mucorales fungi. In this study, we found that the model Mucorales Mucor circinelloides genome carries three copies of the genes encoding the echinocandin target protein ß-(1,3)-d-glucan synthase (fksA, fksB, and fksC). Interestingly, we found that exposing M. circinelloides to micafungin significantly increased the expression of the fksA and fksB genes, resulting in an increased accumulation of ß-(1,3)-d-glucan on the cell walls. However, this overexpression of the fks genes is not directly connected to the intrinsic resistance. Subsequent investigation discovered that the serine/threonine phosphatase calcineurin regulates the expression of fksA and fksB, and the deletion of calcineurin results in a decrease in expression of all three fks genes. Deletion of calcineurin also results in a lower minimum effective concentration (MEC) of micafungin. In addition, we found that duplication of the fks gene is also responsible for the intrinsic resistance, in which lack of either fksA or fksB led a lower MEC of micafungin. Together, these findings demonstrate that calcineurin and fks gene duplication contribute to the intrinsic resistance to micafungin we observe in M. circinelloides.

Rhizopus microsporus as Causative Agent of Mucormycosis in COVID-19 Patient.

BACKGROUND: The pandemic of coronavirus disease (COVID-19) emerged as a fatal infection, especially in immunocompromised patients. Currently, this infection is managed with systemic corticosteroids. Co-infection of CO-VID-19 with opportunistic fungi is increasingly recognized. METHODS: We describe a case of rhino-cerebral mucormycosis 12 days following severe COVID-19 in a diabetic patient. RESULTS: He received 50 mg amphotericin B and surgical debridement. The patient's symptoms improved following medical and surgical intervention. CONCLUSIONS: Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis.

Clinico-Epidemiologic Characteristics of Patients Reported in the Mycotic Infections in COVID-19 Registry.

We update results from the Mycotic Infections in COVID-19 (MUNCO) Registry, May-September 2021. Data collection from May to September 2021 yielded 728 cases from India, Nepal, Bangladesh, Thailand, and the United States. The cases consisted of mostly mucormycosis (97.6%), primarily rhinocerebral, and were analyzed to investigate clinical characteristics associated with negative outcomes. Patients were mostly diabetic (85%) and male (76%), with significant mortality (11.7%). All patients received treatment of coronavirus disease 2019 (COVID-19) as well as antifungal treatment. The crude mortality rate was 11.3% for mucormycosis and 22.7% formixed infections. This study demonstrates the utility of online databases in the collection of high-caliber data.

Microbiology Profile of COVID-19-Associated Rhino-Orbital Mucormycosis Pathogens in South India.

This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye Institute between May and August 2021. Diagnosed clinically and radiologically, 24 patients with ROM were included in the study. Deep nasal swabs or endoscopically collected nasal swabs or orbital tissues were submitted for microbiological evaluation and in vitro susceptibility testing by microbroth dilution for natamycin, amphotericin B, caspofungin, posaconazole, ketoconazole, and voriconazole. Cultures were processed by 28S ribosomal DNA polymerase chain reaction and molecular sequencing. A portion of orbital tissues was also sent for histopathological evaluation. The age of the patients ranged from 27 to 75 (mean 48.58 ± 14.09) years and the majority (79%) were male. Nineteen patients were known to be diabetic prior to developing ROM and 18 patients had recovered from active COVID-19 infection. Thirteen patients had a history of hospitalization during COVID-19 infection and eight received steroids. Of the 24 samples, microbiological evaluation identified Rhizopus arrhizus in 12, Rhizopus microsporus in 9, Lichtheimia ramosa in 2, and Rhizopus delemar in 1. Twelve isolates were tested for antifungal susceptibility and all were susceptible to natamycin and amphotericin B. The susceptibility to posaconazole was high, with minimum inhibitory concentration (MIC) < 2 µg/mL for 10/12 (84%) isolates, whereas the MIC of other drugs varied. Histopathological examination of tissues showed acute fulminant disease, granuloma formation, and vascular invasion by the fungal pathogens in these specimens. Rhizopus arrhizus was predominantly associated with ROM and most isolates were susceptible to amphotericin B and posaconazole. Further studies are needed to corroborate the findings and explain possible underlying links.

Corneal manifestations and treatment among patients with COVID-19-associated rhino-orbito-cerebral mucormycosis.

Purpose: TO report the corneal manifestations in patients with COVID-19-associated rhino-orbito-cerebral mucormycosis (ROCM). Methods: This study was a retrospective, observational, and record-based analysis of patients of ROCM with corneal involvement. Results: A total of 220 patients were diagnosed with ROCM over a period of 3 months. Thirty-two patients had developed corneal manifestations. The mean age at diagnosis was 52.84 ± 12.8 years. The associated risk factors were systemic mucormycosis, uncontrolled diabetes, recent COVID-19 infection, and injudicious use of systemic steroids. Twenty-nine patients were known diabetics, 32 had recent COVID-19 infection, and 13 gave a history of injudicious use of steroids. The right eye (RE) was affected in nine patients, the left eye (LE) in 20 patients, and both eyes in three patients. Nine patients had a round-oval corneal ulcer. One patient each had a perforated corneal ulcer with uveal prolapse, sealed perforated corneal ulcer, spontaneously healed limbal perforation, diffuse corneal haze with hyphemia, panophthalmitis, diffuse corneal stromal abscess, limbal ischemia, anterior uveitis with posterior synechiae, inferior corneal facet, and filamentary keratitis. Three patients each had a corneal melt and inferior conjunctival xerosis with chemosis. Orbital exenteration was performed in six patients. Five patients with corneal ulcers healed. Topical eye drops of amphotericin (0.5 mg/ml) cycloplegic, antiglaucoma medications, and lubricant eye drops were started along with systemic antifungals. Conclusion: Central corneal ulcer was the most common manifestation of mucormycosis. A concentration as low as 0.5 mg/ml of amphotericin eye drops was effective in the treatment.

Impact of COVID-19 pandemic on antifungal consumption: a multicenter retrospective analysis.

BACKGROUND: In the context of COVID-19 pandemic, antifungal overuse may have occurred in our hospitals as it has been previously reported for antibacterials. METHODS: To investigate the impact of COVID-19 on antifungal consumption, a multicenter retrospective study including four medical sites and 14 intensive care units (ICU) was performed. Antifungal consumption and incidences of invasive fungal diseases before and during COVID-19 pandemic, for non-COVID-19 patients and COVID-19 patients, were described. RESULTS: An increase in voriconazole consumption was observed in 2020 compared with 2019 for both the whole hospital and the ICU (+ 40.3% and + 63.7%, respectively), whereas the incidence of invasive aspergillosis significantly increased in slightly lower proportions in the ICU (+ 46%). Caspofungin consumption also increased in 2020 compared to 2019 for both the whole hospital and the ICU (+ 34.9% and + 17.0%, respectively) with an increased incidence of invasive candidiasis in the whole hospital and the ICU but in lower proportions (+ 20.0% and + 10.9%, respectively). CONCLUSIONS: We observed an increased consumption of antifungals including voriconazole and caspofungin in our hospital during the COVID-19 pandemic and explained in part by an increased incidence of invasive fungal diseases in COVID-19 patients. These results are of utmost importance as it raises concern about the urgent need for appropriate antifungal stewardship activities to control antifungal consumption.

Liposomal amphotericin B-the future.

Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.

Coumarin-based combined computational study to design novel drugs against Candida albicans.

Candida species cause the most prevalent fungal illness, candidiasis. Candida albicans is known to cause bloodstream infections. This species is a commensal bacterium, but it can cause hospital-acquired diseases, particularly in COVID-19 patients with impaired immune systems. Candida infections have increased in patients with acute respiratory distress syndrome. Coumarins are both naturally occurring and synthetically produced. In this study, the biological activity of 40 coumarin derivatives was used to create a three-dimensional quantitative structure activity relationship (3D-QSAR) model. The training and test minimum inhibitory concentration values of C. albicans active compounds were split, and a regression model based on statistical data was established. This model served as a foundation for the creation of coumarin derivative QSARs. This is a unique way to create new therapeutic compounds for various ailments. We constructed novel structural coumarin derivatives using the derived QSAR model, and the models were confirmed using molecular docking and molecular dynamics simulation.

Diabetic ketoacidosis and coronavirus disease 2019-associated mucormycosis: a case report.

BACKGROUND: Mucormycosis is a rare, life-threatening fungal infection that affects immunocompromised hosts. Diabetes mellitus is a common predisposing condition and most often presents with rhino-orbital-cerebral infection. Association with coronavirus disease 2019 infection was revealed following a resurgence in cases of mucormycosis during the second wave of the pandemic wherein poorly controlled diabetes mellitus was the most significant risk factor in the affected population. Rhino-orbital-cerebral mucormycosis has a high mortality rate, and cerebral involvement is a poor prognostic factor. Herein, we report a case of newly diagnosed diabetes mellitus with concurrent coronavirus disease 2019 infection complicated by diabetic ketoacidosis and rhinocerebral mucormycosis at presentation, describe the diagnostic and therapeutic challenges, and discuss the interventions that ultimately resulted in a favorable clinical response. CASE PRESENTATION: We describe the case of a previously healthy 13-year-old African American female patient with newly diagnosed diabetes mellitus and concurrent severe acute respiratory syndrome coronavirus 2 infection whose disease course was complicated by rhinocerebral mucormycosis. She presented with fever, altered mental status, and Kussmaul respirations and was diagnosed with diabetic ketoacidosis with concern for cerebral edema. Concern for infectious cerebritis arose due to recurring fevers and persistently altered mental status despite correction of her metabolic derangements. This raised concern for infectious cerebritis and prompted evaluation with serial head imaging, lumbar puncture, and initiation of broad empiric antimicrobial regimen. Head imaging revealed an evolving cerebral abscess, and fungal deoxyribonucleic acid was identified on blood metagenomics testing, which ultimately confirmed the diagnosis of rhinocerebral mucormycosis. Treatment was challenging as she required surgical debridement of the frontal lobe and aggressive antifungal therapy complicated by electrolyte derangements and electrocardiogram changes that necessitated modification of the antimicrobial regimen. Despite these challenges and high mortality rate, the patient was discharged from the hospital in stable condition to inpatient rehabilitation service for reconditioning after prolonged hospitalization. CONCLUSION: Rhinocerebral mucormycosis mortality is associated with delays in therapeutic interventions, thus a high index of suspicion and early recognition were essential for timely initiation of antifungal therapy and surgical debridement.

Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases.

BACKGROUND: The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5-30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. METHODS: The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. RESULTS: Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. CONCLUSIONS: The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.