Rhino-orbital-cerebral mucormycosis as a complication of coronavirus disease 2019

Coronavirus disease 2019 is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2.This disease as well as its various treatments like steroids,antivirals,and antibacterials can alter the immune state of the affected individuals and result in secondary infections such as mucormycosis.Mucormycosis is a well-known opportunistic fungal infection that affects immunocompromised subjects,particularly those with diabetes mellitus,prolonged antibiotic or steroid use,and patients with organ transplantation,neutropenia,and hematological malignancies.Rhino-orbital-cerebral mucormycosis is an aggressive disease owing to its ability to invade the blood vessels by fungal hyphae,leading to necrosis of the involved structures.Large cases were reported from India,indicating that this clinical entity shows a geographical variation.The affected patients are suffering on a clinical spectrum depending on the stage of the disease.Radiological assessment,including computerized tomography and magnetic resonance imaging,is necessary to evaluate the stage of the disease and choose the appropriate surgical treatment.A multidisciplinary approach is required to treat rhino-orbital-cerebral mucormycosis and includes local or intravenous antifungal drugs,debridement of the dead tissues,and appropriate management of any predisposing conditions.The disease has a very poor prognosis with a death rate of 50%.This review aimed to sum-marize the demographic and clinical risk factors,investigations,treatments,and outcomes of coronavirus disease 2019 patients with rhino-orbital-cerebral mucormycosis.

Prognostic factors and clinical features of rhino-orbitalmucormycosis cases:an update for patient and visual survivals

AIM:To determine the frequency of patients’vision survival and prognostic factors and evaluate clinical features in rhino-orbital mucormycosis.METHODS:Forty-three eyes of 43 patients followed up with orbital mucormycosis infections were included in the study.Demographic characteristics of the patients,symptoms at admission,ophthalmologic and non-ophthalmologic examination findings,clinical findings during follow-up,medical and surgical procedures,and complications were recorded.Patient survival was determined by assessing the incidence of mortality,and vision survival was defined as achieving a final visual acuity of at least light perception.RESULTS:Twenty-seven(62.8%)patients were male,and 16(37.2%)were female.When the underlying disease status of the patients was examined,it was observed that all patients had an underlying disease and diabetes constituted the majority(65.2%).Periorbital swelling(69.8%)and ophthalmoplegia(53.5%)were the most common symptoms and findings at the admission of patients with mucormycosis infection.The disease resulted in death in 22(51.2%)patients.The presence of fever and shorter duration of antifungal therapy were associated with lower patient survival.Exenteration surgery was not found to be associated with the survival of the patients.Frozen eye,loss of pupillary light reflex,and development of central retinal artery occlusion were associated with lower vision survival.CONCLUSION:This study presents one of the most extensive patient series in the literature on rhino-orbital mucormycosis.Knowing the patients’symptoms at the time of admission and the clinical findings during the infection process will increase awareness about the disease.

Angioinvasive mucormycosis in burn intensive care units:A case report and review of literature

BACKGROUND Mucormycosis is a rare,rapidly progressive and often fatal fungal infection.The rarity of the condition lends itself to unfamiliarity,delayed treatment,and poor outcomes.Diagnosis of fungal infections early enough to enable appropriate treatment occurs in less than half of affected patients.CASE SUMMARY An 11-year-old girl with a history of 15%total body surface area scald burns involving both lower limbs progressed to develop angioinvasive mucormycosis.This further led to a thrombosis of the right external iliac artery and vein and rapidly progressive necrosis of surrounding soft tissues.She also had dextrocardia and patent foramen ovale.A right hip disarticulation and serial aggressive debridements were performed but she went on to develop systemic sepsis with multisystem involvement and succumbed to the infection.Pathology revealed mucor species with extensive vascular invasion.CONCLUSION This case highlights the importance of maintaining vigilance for mycotic infections and acting appropriately when there are signs of fulminant wound infection.

Isolated cerebral mucormycosis that looks like stroke and brain abscess:A case report and review of the literature

BACKGROUND Cerebral mucormycosis is an infectious disease of the brain caused by fungi of the order Mucorales.These infections are rarely encountered in clinical practice and are often misdiagnosed as cerebral infarction or brain abscess.Increased mortality due to cerebral mucormycosis is closely related to delayed diagnosis and treatment,both of which present unique challenges for clinicians.CASE SUMMARY Cerebral mucormycosis is generally secondary to sinus disease or other disseminated disease.However,in this retrospective study,we report and analyze a case of isolated cerebral mucormycosis.CONCLUSION The constellation of symptoms including headaches,fever,hemiplegia,and changes in mental status taken together with clinical findings of cerebral infarction and brain abscess should raise the possibility of a brain fungal infection.Early diagnosis and prompt initiation of antifungal therapy along with surgery can improve patient survival.

Emerging peril of post-dengue mucormycosis:A case report

Rationale:Dengue fever is a leading cause of death in tropical and subtropical countries.Although most patients have a self-limited febrile illness,the viral infection can induce virus-mediated host changes,making immunocompetent persons susceptible to deadly fungal infections.However,there are only a few reports of such an association.Here we present a case of this deadly co-infection.Patient’s Concern:A 17-year-old male patient was diagnosed with dengue fever.He presented to us with facial swelling,periorbital edema,and black discoloration over the palate during the second week of his illness.Diagnosis:Diagnostic tests confirmed the presence of fungal hyphae.A diagnosis of post-dengue mucormycosis was made.No other comorbidity or underlying immune deficit was detected.Interventions:The patient underwent surgical debridement and antifungal treatment.Outcomes:The patient recovered and showed signs of palatal healing with an advancing mucosal edge.Lessons:Dengue virus and mucor co-infection has brought to light a new pathogenic paradigm.Clinicians need to be aware of this emerging medical condition and maintain a high index of suspicion for mucor co-infections while treating dengue patients.

Mortality and Morbidity among COVID-19-Associated Mucormycosis Patients in Iran: A Prospective Cohort Study

Background: The key contribution of this paper is from investigating the mortality and morbidity rates and related factors associated with COVID-19-associated-mucormycosis among Iranian patients. The existing literature is scarce on this topic, particularly in the context of Iran. The present study investigates mortality and morbidity among 62 confirmed COVID-19-associated-mucormycosis Iranian patients in relation to their demographic characteristics, laboratory test results, predisposing factors, and COVID-related factors. Material and Methods: In this prospective cohort study, the patients were identified in the fifth wave of the disease, between 1st August and 15th October 2021, with data collected at baseline with a three-week follow-up. This was a multicenter investigation with patients admitted to two clinics in Iran. 62 participants were admitted, with the key criteria of them being COVID-19-associated-mucormycosis patients. 53 out of 60 patients underwent corticosteroid therapy and debridement surgery. Intravenous remdesivir (200 mg/ kg/day at day 1, 100 mg/kg/day in following days for up to 5 days) and corticosteroids were administered for 53 out 54 patients. Oxygen therapy was only needed for 30% (n = 19) of the patients. Results: A 40% mortality rate was observed within the three-week follow-up, with deaths concentrated among those with controlled diabetes mellitus (61%) and long-term diabetes mellitus patients (an average of eight versus four years). Higher mortality was also observed in patients with higher leucocytes and those with rhino-orbital-cerebral (59%), followed by nasal (55.6%) mucormycosis. Among survivors, 32% were reinfected, and 56% suffered from loss of vision. Conclusion: The study concludes that mucormycosis is associated with a higher mortality rate among COVID-19 patients with diabetes mellitus, particularly corticosteroid recipients. Thus, urgent attention to this coinfection is warranted in Iran.

Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult:A case report

BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients.This disease usually develops acutely and progresses rapidly,often leading to a poor clinical prognosis.Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.CASE SUMMARY A 43-year-old man,who was a house improvement worker with a long history of occupational dust exposure,presented with an irritating cough that had lasted for two months.The patient was previously in good health,without dysglycemia or any known immunodeficiencies.Chest computed tomography revealed a mass in the left lower lobe,measuring approximately 6 cm in diameter,which was suspected to be primary lung carcinoma complicated with obstructive pneumonia.Thoracoscopic-assisted left lower lobectomy was performed,and metagenomic next-generation sequencing detection,along with special pathological staining of surgical specimens,suggested Rhizopus microsporus infection.Postoperatively,the patient’s respiratory symptoms were relieved,and no signs of recurrence were found during the six-month follow-up.CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency.The patient’s surgical outcome was excellent,reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.

Invasive rhinocerebral mucormycosis:Imaging the temporal evolution of disease in post COVID-19 case with diabetes:A case report

BACKGROUND Rhinocerebral mucormycosis(RCM)is a rare,fatal,invasive fungal infection infecting mainly patients with immunocompromised conditions,such as diabetes mellitus,hematologic malignancies,and organ transplantations.Coronavirus disease 2019(COVID-19)disease in these patients further weakens the immune system due to several factors,including hypoxia,corticosteroid usage(further increasing hyperglycemic status),mechanical ventilation,increased serum ferritin levels,endothelitis due to free radicals,and glucose receptor protein upregulation.Timely diagnosis,judicious treatment decisions,and diabetes control with proper treatment guidelines in patients with coexisting COVID-19 disease can reduce complication rates and improve survival.CASE SUMMARY A 75-year-old male patient with diabetes and hypertension diagnosed with COVID-19 presented to the emergency department.Laboratory examinations revealed elevated blood glucose levels,as well as ketone bodies in the urine.He was treated with oxygen and steroids,as well as insulin to correct blood glucose levels.He complained of a headache 10 d later,and imaging demonstrated mucosal thickening in bilateral sphenoidal,ethmoidal,and maxillary sinuses with hyperdense foci in the right maxillary sinus but without central nervous system involvement.Surgical debridement was performed,and a histopathological study revealed fungi hyphae.Systemic antifungals(amphotericin b and posaconazole)were administered.Subsequently,on 15th day he developed right lower limb weakness and left lateral rectus palsy.There was slow but steady progress,and he was discharged.However,he presented to emergency department 1mo later with altered sensorium and poor control of diabetes resulted in an intracranial spread of mucormycosis,which ultimately led to the patient’s poor prognosis and slow recovery.CONCLUSION Prompt early diagnosis,judicious treatment decisions,and diabetes control with proper treatment guidelines are necessary in patients with COVID-19 associated invasive RCM to reduce complication rates and improve patient survival.

Hepatic mucormycosis mimicking hilar cholangiocarcinoma:A case report and literature review

Mucormycosis is a rare but invasive opportunistic fungal infection associated with a high mortality rate,and normally occurs in immunocompromised patients. In this report,we describe an immunocompetent patient suffering from hepatic mucormycosis secondary to adrenal mucormycosis,which masquerades as hilar cholangiocarcinoma. After surgical procedure and treatment with amphotericin B and itraconazole,the patient recovered well and had a 2-year infection-free survival. To our knowledge,this special clinical manifestation of hepatic infection as well as adrenal mucormycosis has not been reported to date. Mean-while,this is the first case of an immunocompetent patient with both adrenal and hepatic mucormycosis who has been treated successfully.

Mucormycosis in a diabetic ketoacidosis patient

Oral cavity is considered to be a kaleidoscope for body's general health.Many systemic conditions do present with diverse oral manifestations.Mucormycosis involving the oral cavity is one such entity that presents as necrosis of bone in immunocompromised patients.Mucormycosis is an opportunistic fungal infection that mainly affects the patients with uncontrolled diabetes mellitus.Hereby,we report a case of mucormycosis involving the palate in a patient with diabetic ketoacidosis.

Ileocolonic mucormycosis in adult immunocompromised patients:A surgeon's perspective

We report three cases of ileocolic mucormycosis in adult immunocompromised patients presenting as acute abdomen.All patients underwent laparotomy but two of them died from multiorgan failure before the diagnoses were confirmed.The diagnosis of gastrointestinal mucormycosis is rarely suspected,and antemortem diagnosis is made in only 25%-50% of cases.These cases illustrate the difficulty encountered by surgeons in managing acute abdomen in neutropenic patients with hematological malignancy.The management of colonic mucormycosis in the published literature is also reviewed.

COVID-19-associated mucormycosis and treatments

In the current pandemic,COVID-19 patients with predisposing factors are at an increased risk of mucormycosis,an uncommon angioinvasive infection that is caused by fungi with Mucor genus which is mainly found in plants and soil.Mucormycosis development in COVID-19 patient is related to various factors,such as diabetes,immunocompromise and neutropenia.Excessive use of glucocorticoids for the treatment of critically ill COVID-19 patients also leads to opportunistic infections,such as pulmonary aspergillosis.COVID-19 patients with mucormycosis have a very high mortality rate.This review describes the pathogenesis and various treatment approaches for mucormycosis in COVID-19 patients,including medicinal plants,conventional therapies,adjunct and combination therapies.

Gastric mucormycosis: A case report

Mucormycosis is a rare fungal infection which is largely diagnosed in immune-compromised patients. The infection can cause pulmonary, rhinocerebral, skin and soft tissue, central nervous system and gastrointestinal system. The gastrointestinal involvement is the rarest presentation, especially the stomach. We present a 38 years old HIV positive female seen in Steve Biko Academic Hospital with 2 wk history of cough, shortness of breath and lethargy. She was clinically found to be pale, pyrexial, dyspnoea and had severe oral thrush. Blood tests revealed hemoglobin of 6 g/dL CD4 count of 63 cells/uL. Chest X-ray showed multi-lobe pneumonia and gastroscopy confirmed esophageal candidiasis and nodular gastritis. She continued to deteriorate despite antibiotics, antifungal and antituberculous treatment. She developed upper gastrointestinal bleed on day 34, and gastroscopy showed a plaque like lesion in the stomach, histology of which confirmed mucormycosis. She improved on Amphotericin B but subsequently deteriorated and demised a few days later. These cases illustrate the occurrence of a rare fungal infection of the stomach and the poor mortality when diagnosis is delayed. Mucormycosis can co-exist with candidiasis and clinicians should have a high index of suspicion especially in patients not responding to appropriate treatment.

Rhino-orbito-cerebral mucormycosis complicated with an ophthalmic artery occlusion followed by subarachnoid hemorrhage

A 70-year-old female with poorly controlled diabetes developed sudden visual loss, ptosis and complete ophthalmoplegia of the right eye. Funduscopic examination showed the pale retina and the cherry red spot in the right eye. Fluorescein angiography and indocyanine green angiography demonstrated the absence of retinal arterial filling and choroidal perfusion in the right eye even 20 minutes after injecting the dye. The patient was diagnosed with right ophthalmic artery occlusion. Computed tomography (CT) showed diffuse mucosal thickening in the right ethmoidal sinus. Based on the clinical findings and endoscopic biopsy result, mucormycosis was confirmed. Amphotericin B (40 mg/day) and ceftriaxone (2 g/day) were intravenously administered. Despite the improvement of the right ethmoidal sinusitis and the right proptosis, the patient deteriorated into a comatose state after 19 days of systemic amphotericin B therapy. Although the previous CT showed no cerebral aneurysm, a repeated CT showed newly developed posterior communicating artery aneurysm and the subarachnoid hemorrhage. Despite the amphotericin B treatment and the improvement of the sinusitis, mucormycosis could cause sudden cerebral aneurysm rupture and subarachnoid hemorrhage resulting in coma.

Clinical outcome of orbital apex syndrome in COVID associated mucormycosis patients in a tertiary care hospital

AIM: To share clinical pattern of presentation, the modalities of surgical intervention and the one month postsurgical outcome of rhino-orbito-mucormycosis(ROCM) cases.METHODS: All COVID associated mucormycosis(CAM) patients underwent comprehensive multidisciplinar y examination by ophthalmologist, otorhinolaryngologist and physician. Patients with clinical and radiological evidence of orbital apex involvement were included in the study. Appropriate medical and surgical intervention were done to each patient. Patients were followed up one-month post intervention. RESULTS: Out of 89 CAM patients, 31(34.8%) had orbital apex syndrome. Sixty-six(74.2%) of such patients had pre-existing diabetes mellitus, 18(58%) patients had prior documented use of steroid use, and 55(61.8%) had no light perception(LP) presenting vision. Blepharoptosis, proptosis, complete ophthalmoplegia were common clinical findings. Seventeen(19.1%) of such patients had variable amount of cavernous sinus involvement. Endoscopic debridement of paranasal sinuses and orbit with or without eyelid sparing limited orbital exenteration was done in most cases, 34(38.2%) patients could retain vision in the affected eye. CONCLUSION: Orbital apex involvement in CAM patients occur very fast. It not only leads to loss of vision but also sacrifice of the eyeball, orbital contents and eyelids. Early diagnosis and prompt intervention can preserve life, vision and spare mutilating surgeries.

Manifestations and risk factors of COVID-19 and mucormycosis:A mini-review

Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 has become a pandemic disease.It also increases the risk of co-infections.Mucormycosis is a severe fungal infectious disease and its causative agent,mucormycetes,belongs to an opportunist fungus Mucoraceae family.Mucormycosis in COVID-19 patients with mucormycosis presents an additional challenge worldwide.Mucormycosis shares certain risk factors and signs and symptoms with COVID-19.In this review,we summarize manifestations and risk factors of mucormycosis and COVID-19.

Colonic mucormycosis presented with ischemic colitis in a liver transplant recipient

Mucormycosis is an uncommon opportunistic fungal infection with high mortality in liver transplant recipients. Mucormycosis of the gastrointestinal tract can manifest with features similar to ischemic colitis. Typically signs and symptoms of non-gangrenous ischemic colitis resolve spontaneously within 24-48 h. On the other hand, the clinical course of the mucormycosis is commonly fulminant. We encountered a case of invasive fungal colitis presenting with abdominal pain and hematochezia in a liver transplant recipient. Endoscopic examination showed multiple shallow ulcerations and edema with mucosal friabilities on the sigmoid and distal descending colon, which was consistent with ischemic colitis. However, the histological examination obtained from endoscopic biopsies showed fungal hyphae withsurrounding inflammatory cells and mucosal necrosis. The patient was successfully managed with antifungal agent without surgical treatment. Thus, early diagnosis and treatment is essential for improving the prognosis of invasive fungal infection after liver transplantation.

F-18 fluorodeoxyglucose positron emission tomography/computed tomography image of gastric mucormycosis mimicking advanced gastric cancer: A case report

BACKGROUND Mucormycosis is a very rare fungal infection,and its prognosis is poor.Most common sites of infection are the sinuses,lung,or skin,and gastric involvement is uncommon.The standard antifungal therapy is the treatment of choice for gastric mucormycosis.However,the symptoms of gastric mucormycosis are varied and the early diagnosis is not easy.CASE SUMMARY I report a 53-year-old alcoholic man,who was admitted due to epigastric pain.The upper gastrointestinal endoscopy revealed a huge ulcer lesion in the stomach,which was suspected to be gastric cancer.F-18 fluorodeoxyglucose positron emission tomography/computed tomography(F-18 FDG PET/CT)showed diffusely intense FDG uptake at the ulcer lesion of the stomach,and several enlarged hypermetabolic lymph nodes were noted at the left gastric chain.Although,endoscopy and F-18 FDG PET/CT findings suggested advanced gastric cancer with regional lymph node metastases,there was no cancer cells in the biopsy results and multiple fungal hyphae were noted in the periodic acid-Schiff stained image.CONCLUSION He was diagnosed with gastric mucormycosis and successfully underwent amphotericin B and posaconazole treatment.

Pharmacokinetic/Pharmacodynamic Analysis the Probability of Target Attainment of Posaconazole against <i>Mucorales</i>Species in Patients with Mucormycosis

The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.

Mucormycosis: A Review on Environmental Fungal Spores and Seasonal Variation of Human Disease

Mucormycosis is on the rise especially among patients with immunosuppressive conditions. There seems to be more cases seen at the end of summer and towards early autumn. Several studies have attempted to look at the seasonal variations of fungal pathogens in variou indoor and outdoor settings. Only two reports, both from the Middle East, have addressed the relationship of mucormycosis in human disease with climate conditions. In this paper we review, the relationship of indoor and outdoor fungal particulates to the weather conditions and the reported seasonal variation of human cases.