Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Cost-Effectiveness Analysis of Liposomal Amphotericin B Versus Isavuconazole for Treating Mucormycosis in the Consolidation Phase from the Perspective of the Brazilian Unified Health System

Objectives: Mucormycosis is a rare invasive fungal infection with high lethality, affecting mainly patients with hematological neoplasia, decompensated diabetes, and covid-19 infection. The aim was to perform a cost-effectiveness analysis of liposomal Amphotericin B (standard treatment) versus isavuconazole for treating mucormycosis in the consolidation phase from the perspective of the Brazilian Unified Health System. Method(s): A decision tree model was built. The analysis considered the costs of the treatment over a six-month time horizon. This included hospitalization during the entire course of treatment and the expenditures related to dialysis, complication occurring in 5% (3%-6%) of cases treated with the Amphotericin B. Appointments with specialists were included in the isavuconazole arm, and amphotericin B was used if the patient failed to respond to isavuconazole. The utility of the patient with mucormycosis, cured and with renal failure was estimated. Uncertainties were assessed through probabilistic and deterministic sensitivity analyses. Result(s): The average cost of amphotericin B and isavuconazole arm was R$1.054.874,39 and R$522.344,05, respectively. The utility was 0.479 with amphotericin B and 0.480 with isavuconazole. The ICER was R$ -684,494,237 (dominant). In deterministic sensitivity analysis, the probability of dialysis was the variable with the greatest impact. In probabilistic analysis, the ICER is distributed in the right and left lower quadrant, the acceptability curve for all the scenarios analyzed is favorable for isavuconazole. The budget impact suggests a potential savings of between R$ 350 million and R$ 415 million over five years. Conclusion(s): The treatment of mucormycosis during the consolidation phase with isavuconazole represents a lower cost, besides the convenience of oral treatment and reduced incidence of severe adverse events, with mortality similar to the Amphotericin B arm. In Brazil, the formulation of posaconazole approved is inadequate for treating mucormycosis during the consolidation phase, therefore isavuconazole is the single oral drug available.Copyright © 2023

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

Case Reports on Black Fungus of the Gastrointestinal Tract: A New Complication in COVID-19 Patients.

Gastrointestinal mucormycosis is a rare disease with a significant mortality rate, even when promptly diagnosed and treated. An unusual complication was observed in India during the second wave of coronavirus disease 2019 (COVID-19). Two incidences of gastric mucormycosis were found. A 53-year-old male patient with a history of COVID-19 one month earlier came into the intensive care unit. After admission, the patient developed hematemesis, which was initially treated with blood transfusions and digital subtraction angiography embolization. Esophagogastroduodenoscopy (EGD) revealed a large ulcer with a clot in the stomach. During an exploratory laparotomy, the proximal stomach was necrotic. Histopathological examination confirmed mucormycosis. The patient was started on antifungals, but despite rigorous therapy, the patient died on the tenth postoperative day. Another patient, an 82-year-old male with a history of COVID-19, arrived with hematemesis two weeks earlier and was treated conservatively. EGD revealed a large white-based ulcer with abundant slough along the larger curvature of the body. Mucormycosis was verified by biopsy. He was treated with amphotericin B and isavuconazole. He was discharged after two weeks in a stable condition. Despite quick detection and aggressive treatment, the prognosis is poor. In the second case, prompt diagnosis and treatment saved the patient's life.

The challenges of the genome-based identification of antifungal resistance in the clinical routine.

The increasing number of chronic and life-threatening infections caused by antimicrobial resistant fungal isolates is of critical concern. Low DNA sequencing cost may facilitate the identification of the genomic profile leading to resistance, the resistome, to rationally optimize the design of antifungal therapies. However, compared to bacteria, initiatives for resistome detection in eukaryotic pathogens are underdeveloped. Firstly, reported mutations in antifungal targets leading to reduced susceptibility must be extensively collected from the literature to generate comprehensive databases. This information should be complemented with specific laboratory screenings to detect the highest number possible of relevant genetic changes in primary targets and associations between resistance and other genomic markers. Strikingly, some drug resistant strains experience high-level genetic changes such as ploidy variation as much as duplications and reorganizations of specific chromosomes. Such variations involve allelic dominance, gene dosage increments and target expression regime effects that should be explicitly parameterized in antifungal resistome prediction algorithms. Clinical data indicate that predictors need to consider the precise pathogen species and drug levels of detail, instead of just genus and drug class. The concomitant needs for mutation accuracy and assembly quality assurance suggest hybrid sequencing approaches involving third-generation methods will be utilized. Moreover, fatal fast infections, like fungemia and meningitis, will further require both sequencing and analysis facilities are available in-house. Altogether, the complex nature of antifungal resistance demands extensive sequencing, data acquisition and processing, bioinformatic analysis pipelines, and standard protocols to be accomplished prior to genome-based protocols are applied in the clinical setting.

A Case Series of Kodamaea Ohmeri Infection: The Hidden Threat Unleashed

Intro: Kodamaea ohmeri, previously known as Pichia ohmeri, is an ascomycetous yeast that has emerged as an important cause of fungemia in immunocompromised patients. During the anamorphic stage this organism is also known as Candida guillermondii var. membranaefaciens. Method(s): We report five cases of Kodamaea ohmeri encountered from multicenter in Malaysia. Antifungal agent of choice will be discussed based on literature review. Finding(s): The cases were: (1) a contaminated peritoneal fluid in an adult patient on peritoneal dialysis;(2) a 60-year-old man with infected diabetic foot isolated K. ohmeri from a bone sample. Both cases discharged well without active antifungal fungal therapy. We observed fatality cases involving (3) an old man with underlying gastric adenocarcinoma who complicated with catheter- related bloodstream infection caused by K. ohmeri;(4) a patient with ventilator- associated pneumonia and septicaemic shock secondary to perforated terminal ileum;(5) and a severely ill COVID-19 stage 5b patient who passed away due to systemic fungaemia caused by K. ohmeri. Discussion(s): All three fatal cases received either amphotericin B or caspofungin as active antifungal agent. Literature evidence has shown that 40% of patient met demise despite on active antifungal agent, suggesting that currently no definitive antifungal agent proven to be a superior treatment option for K. ohmeri infection. Removal of indwelling medical device combined with antifungal therapy has favorable clinical outcome. Conclusion(s): Therefore, K. ohmeri infection in severely ill patients should be considered as a critical condition. Potential of alternative antifungal combinations need to be explored for an effective treatment option.Copyright © 2023

COVID-19 and Mucormycosis

In early December 2019, several cases of pneumonia of unknown etiology were reported from Wuhan, Hubei province, China. The disease resembles severe acute respiratory syndrome coronavirus (SARS CoV) of 2012 and was subsequently named SARS CoV-2 causing the 2019-novel coronavirus disease (COVID-19) by the World Health Organization (WHO). The first case of COVID-19 in India was reported on January 30, 2020. In the first wave, daily cases peaked in mid-September 2020 and began to drop by January 2021. However, a second wave beginning in March 2021 was experienced which was much larger than the first, with extreme shortages of hospital beds, oxygen cylinders, and other medicines including vaccines in parts of the country. In the second wave, an association of COVID-19 patients with mucormycosis further complicated the situation. COVID-19 associated mucormycosis (CAM) has been increasingly reported particularly among patients with uncontrolled diabetes. An increase in CAM cases could be probably due to immunosuppression caused by the use of steroids, other immunomodulators like tocilizumab. Rhino-orbitalcerebral mucormycosis is the most common presentation. The most common causative agent isolated is Rhizopus arrhizus. Simple KOH examination with broad, ribbon-like, aseptate hyphae that branch at right angles is diagnostic of mucormycosis. This can be further confirmed by culture examination. However, newer tests like MALDI-TOF for species identification are also being explored. The main treatment modality is surgical debridement, removing all the infected, dead, and necrotic tissue followed by simultaneous administration of antifungal antibiotics in the form of Amphotericin B. Liposomal amphotericin B is the drug of choice, however, if not available, amphotericin B deoxycholate, posaconazole, and isavuconazole can be given for the treatment of CAM. Prognosis and clinical improvement depend upon the stage of disease, the surgical management as well as the availability and administration of antifungal drugs. In media, mucormycosis is being projected as black fungus throughout this pandemic, though it is a misnomer and should not be used in the medical literature. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Novel role of 18F- FDG PET/CT in rhinosinonasal mucormycosis in the era of covid-19 infection

Objectives: In the Covid-19 era, there was a surge in the cases of a life-threatening infection of rhinosinonasal mucormycosis. Mucormycosis, popularly known as black fungus, is an infection caused by mycetes mucorales, an aseptate hyphae. Presently, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used imaging modalities for the management of patients with rhinosinonasal mucormycosis. The present study was aimed to evaluate the role of 18F- FDG PET/CT in the detection of recurrent or residual disease in post-surgical or post antifungal therapy in these patients for further management. Method(s): A total of 10 patients were included in this pilot study of Covid-19 positive patients and histologically proven mucormycosis (by KOH mount). 18F- FDG PET/CT was performed to assess the disease status in 6 postoperative/ post debridement patients and response to antifungal therapy in 4 patients, at an interval of 40 (range = 27-66) days post intervention. Result(s): The mean age of the patients was 45.0 +/- 11.65 years. The male: female ratio was 9:1. The common clinical presentation was ipsilateral facial or orbital pain and swelling. Covid-19 infection was positive in all the patients except one who had CT finding with HRCT score of 10/25 and hence was considered as post Covid-19 infection. Six out of 10 patients were diabetic on oral hypoglycaemic agents or insulin. All patients had a baseline CT/MRI for staging the initial extent of the disease. Surgical debridement was done in 6 out of the 10 patients followed by antifungal therapy (Liposomal Amphotericin B and Pozaconazole). Remaining four patients were treated with antifungal therapy. PET/CTwas performed after an average of 40 days of surgical/medical intervention, in whom clinical symptoms persisted or worsened even on antifungal therapy. 18F-FDG PET/CT showed metabolically active residual disease in all the patients with a mean SUVmax of 9.78 +/- 4.03. Conclusion(s): In the era of ongoing Covid-19 infection, black fungus has been a debilitating disease with high mortality and morbidity. Present study demonstrated that 18F-FDG PET/CT can be an efficient imaging tool for an early surgical/ medical treatment response assessment and restaging.

Outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) as an adjuvant therapy for rhino-orbital-cerebral mucormycosis (ROCM) following COVID-19.

PURPOSE: To assess the outcomes of transcutaneous retrobulbar Amphotericin B (TRAMB) for rhino-orbital-cerebral-mucormycosis (ROCM) post-COVID-19, as an adjuvant to standard systemic antifungal therapy. METHODS: In this prospective cohort study involving ROCM patients with clinical/radiological orbital involvement, 44 eyes with ROCM stage ≥ 3B received TRAMB for 7 consecutive days with liposomal Amphotericin-B (3.5 mg/ml) with a minimum clinical and radiological follow-up of 3 months. All patients received standard systemic antifungal therapy also as per institutional protocol. Data pertaining to demography, systemic status, clinical involvement, imaging, surgical/medical management were also recorded. Potential eyes for exenteration were excluded. Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 12 Given name: [Mahendra Kumar ] Last name [Garg]. Also, kindly confirm the details in the metadata are correct.All author names are presented accurately. Details in the metadata are correct. Thank you. RESULTS: Forty-four eyes of 42 patients were included, out of which 30 had diabetes mellitus & 22 had received steroid/oxygen treatment during COVID-19 infection. Forty eyes showed improvement or stable disease on follow-up on radiology. Four eyes which showed progression of the disease in orbit were reaugmented with TRAMB. No patient required exenteration. Subconjunctival haemorrhage occurred in six eyes and temporary blurring of vision in four eyes after TRAMB which resolved spontaneously. CONCLUSION: TRAMB, as an adjuvant to standard systemic antifungal therapy, is associated with a significant reduction or stabilisation of orbital involvement. TRAMB should be considered as an adjuvant therapy for ROCM to reduce disease progression as well as to preserve globe or sight. It has a promising role in preventing potential orbital exenterations.

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Post-Covid mucormycosis presenting as retropharyngeal abscess: a rare case report

Background: Post-Covid retropharyngeal mucormycosis is a rare presentation, and no case has been reported in literature until date. Case presentation: A-32-year-old female post Covid presented to our OPD with history of dysphagia and with a history of steroid intake. Radiology confirmed it as retropharyngeal abscess. Endoscopic-guided aspiration was done. HPE (histopathological examination) revealed classic broad aseptate hyphae of mucormycosis. Patient was managed conservatively with broad-spectrum antifungal. Conclusion(s): Retropharyngeal mucormycosis is a rare entity in Covid era. Rapid diagnosis and management are needed to save life of an individual, or results could be fatal.Copyright © 2022, The Author(s).

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Renal safety of liposomal amphotericin B in critically ill mechanically ventilated patients with SARS-CoV-2 pneumonia

Introduction: Liposomal amphotericin B (L-AmB) represent a good treatment strategy for critically ill patients according to its unique pharmacological characteristics and a relatively broad spectrum of action. The aim of the present study is to asses the impact on renal function of L-AmB during the first days of ICU admission in critically ill patients. Method(s): Retrospective, single-center case series of patients with SARS-CoV-2 pneumonia admitted in ICU. Setting(s): 19-bed medical-surgical ICU of a community hospital. Time of study: 2 years. Study variables: APACHE II and SOFA at admission, clinical characteristics, oliguria and creatinine level at admission and 72 h after L-AmB treatment were recorded. Oliguria was defined as urinary output less than 400 ml per day or less than 20 ml per hour. Two groups of patients were selected according to whether or not they received anticipated antifungal treatment pending microbiologic confirmation or discarding of aspergillosis;dosage of L-AmB was 3 mg/kg/d. Statistical analysis: Data were analyzed by SPSS 18 and quantitative variables were expressed as a mean +/- standard deviation. Result(s): 160 patients were included, 102 who received 3 days of anticipated treatment with L-AmB at ICU admission or at the beginning of mechanical ventilation were compared with patients without this treatment. There were not differences in age, median 65 [57-71] years, gender with 28% female and BMI (kg/m2), 30,4 [26,6-33,2]. APACHE II at admission was higher in the treated group of patients 17 [12-23] vs 12 [9-14]. SOFA was 7 [4-8] in the treated group of patients vs 6 [3-8]. There were not differences in urinary output between groups during the three first days of ICU stay. Table 1 shows creatinine levels. Conclusion(s): According to our retrospective analysis, L-AmB is safe in the first days of treatment in critically ill patients admitted in ICU requiring mechanical ventilation.

COVID-19-related acute invasive fungal rhinosinusitis: risk factors associated with mortality

Background: Acute invasive fungal rhinosinusitis (AIFRS) is a rare aggressive life-threatening infection that affects immunocompromised individuals. Recently, an increase in the incidence of this infection has been reported in patients who have SARS-CoV-2 infection or recently recovered. This study was to assess the outcome and define risk factors that might affect the outcome in SARS-CoV-2-related AIFRS. A prospective observational study included 54 patients diagnosed with SARS-CoV-2-related AIFRS. Controlling the predisposing factors, systemic antifungal, and early surgical debridement was performed. The mortality rate was calculated. Age, sex, underlying risk factors, the extent of the disease, debridement technique, and other biochemical variables were evaluated regarding their impact on survival. Patients were followed up for 3 months. Result(s): Fifty-four patients with a mean age of 48.1 years. Diabetes mellitus was the most common comorbidity affecting 52 patients (96.3%). Intracranial and intraorbital extension had a predictive value for mortality (P value 0.050 and 0.049 respectively). However, only intracranial extension was the independent predictor of mortality. Biochemical variables were higher than the normal range, but only serum ferritin level above 165 ng/ml was an independent predictor of mortality in patients with AIFR. The mortality rate was 38.9%. Conclusion(s): The extent of the disease has a major impact on survival, so early diagnosis of AIFRS within patients infected with SARS-CoV-2 or recently recovered is essential to reduce mortality.Copyright © 2022, The Author(s).

Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study.

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.

Tracing, Tracking and Treating COVID-19 Associated Rhino-Orbito Cerebral Mucormycosis (ROCM).

Surge in the number of mucormycosis cases following second wave of coronavirus disease-19 (COVID-19) infection posed several diagnostic and prognostic challenges. This study was aimed to describe clinical, diagnostic features and survival outcomes among patients of mucormycosis in post COVID-19 context. Retrospective chart review. This study included 44 COVID-19 positive screened cases who presented with clinical features suggestive of mucormycosis. Demography, clinical profile, diagnostic findings, and the treatment outcome are studied. Medical and surgical outcomes are summarised as frequencies and percentages. The reliability of microbiological, and radiological findings against the pathological findings was analyzed using Kappa statistics (k). Based on constellation of microbiological, pathological and radiological findings 28 cases (63%) confirmed with mucormycosis infection. The mean (SD) age was 54.9 (12.9) years and two-third were males. The majority (90%) of cases presented with the feature of facial swelling, headache nasal blockade. Inpatient care for treatment of COVID-19 was recorded in 33 (75%). Diabetes mellitus was the commonest comorbidity in 27 (61.4%), 38 (86.4%) cases were treated by steroids and 30 (68.2%) were given oxygen therapy. There is a strong agreement (k = 0.83) between pathological and microbiological investigations. In thirty-eight cases (86.3%) remission was achieved when assessed after 8 weeks. Of the 44 cases, four patients died. The results of the current study suggest that the disease residues and/or recurrences in critical areas are frequent in mucormycosis. However, using the strategy of screening at risk patients, diagnosing, treating them with combination of antifungals, surgical debridement, and timely follow up may help in improving outcomes as compared to pre COVID-19 era.

Wave of Invasive Fungal Disease on the Shores of COVID-19: A Case Series of COVID-19 Associated Rhino-Orbital Fungal Rhinosinusitis and Literature Review.

Coronavirus disease 2019 (COVID-19) may be associated with a wide range of bacterial and fungal co-infections. Acute invasive fungal sinusitis is an aggressive infection affecting immunocompromised patients and high mortality rate. Here, in this case series, we have reviewed three cases of COVID-19 associated rhino-orbital invasive fungal disease. Patients with COVID-19 associated pneumonia with diabetes mellitus are at an increased risk of developing invasive pulmonary fungal infections probably due to their reduced immunological competence. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. Physicians should be aware of and should have high index of suspicion of possible fungal infection in post COVID-19 patients. Aggressive management both medical and surgical, is required to improve outcomes of secondary invasive fungal infections in patients with COVID-19 infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03213-y.

Mucormycosis of Paranasal Sinuses of Odontogenic Origin Post COVID19 Infection: A Case Series.

The Severe acute respiratory syndrome and the Middle East respiratory syndromes emerged in 2002 and 2012 respectively. Currently the world is witnessing a global pandemic caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS CoV- 2) causing the Coronavirus 2019 (COVID-19). Mucormycosis is a fungal infection primarily affecting individuals with an immunocompromised state like diabetes mellitus, malignancies etc. Patients who have or have had COVID-19 infection with pre-existing uncontrolled Type 2 Diabetes mellitus are presumably more vulnerable for emergence of fungal infections cases. This article presents a report of 6 cases with histopathological proven mucormycosis associated with COVID-19 and uncontrolled Diabetes mellitus.