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Purpose: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). Methods: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. Results: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. Conclusion: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome. [ABSTRACT FROM AUTHOR]

Invasive mucormycosis is a refractory fungal infection. Central nervous system (CNS) mucormycosis is a rare complication caused by infiltration from the paranasal sinuses or hematogenous dissemination. Here, we present a case of a brain abscess, due to mucormycosis, diagnosed using burr craniotomy. A 25-year-old Japanese woman with relapsed-refractory acute lymphoblastic leukemia underwent cord blood transplantation (CBT). The patient experienced prolonged and profound neutropenia, and oral voriconazole was administered as primary antifungal prophylaxis. The patient received a conditioning regimen on day −11 and complained of aphasia and right hemiparesis on day −6. Magnetic resonance imaging (MRI) revealed a T2-weighted high-intensity area in the left frontal cortex. A brain abscess was suspected, and liposomal amphotericin B (L-AMB) administration was started. The patient underwent CBT as scheduled and underwent neutrophil engraftment on day 14. Although the patient achieved complete remission on day 28, her consciousness level gradually deteriorated. MRI revealed an enlarged brain lesion with a midline shift sign, suggesting brain herniation. Craniotomy was performed to relieve intracranial pressure and drain the abscess on day 38, and a diagnosis of cerebral mucormycosis was confirmed. The L-AMB dose was increased to 10 mg/kg on day 43. Although the patient's consciousness level improved, she died of hemorrhagic cystitis and aspiration pneumonia. Cerebral mucormycosis should be suspected if neurological symptoms are observed in stem cell transplant recipients. Prompt commencement of antifungal therapy and debridement are crucial because mucormycosis has a poor prognosis. [ABSTRACT FROM AUTHOR]

Mucormycosis is an opportunistic infection seen in immunocompromised patients or in surgical and trauma settings with Mucorales wound contamination. In immunocompetent people, disseminated mucormycosis is uncommon. To ensure survival, patients with mucormycosis require early diagnosis and aggressive treatment using a multi-modality approach. We present a case of disseminated mucormycosis in an immunocompetent patient who also had pulmonary embolism and gastrointestinal bleeding. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified retrospectively by a positive IgM against SARS-CoV-2, was the only risk factor present. This report emphasizes the increased risk of mucormycosis and thromboembolic complications following a recent SARS-CoV-2 infection, as well as its successful treatment with medical therapy alone.

Invasive fungal diseases (IFD) still cause substantial morbidity and mortality, and new therapeutic approaches are urgently needed. Recent data suggest a benefit of checkpoint inhibitors (ICI). We report the case of a diabetic patient with refractory IFD following a SARSCoV-2 infection treated by ICI and interferon-gamma associated with antifungal treatment. [ABSTRACT FROM AUTHOR]

Context: During the challenging second wave of the COVID-19 pandemic, we encountered a most dreadful fungal infection in the form of COVID-associated mucormycosis (CAM), with a varied pattern of presentation from previous experience. Patients presented with simple fungal sinusitis or more complicated brain abscesses, and newer manifestations such as skull osteomyelitis. We report our findings and innovative treatment strategies used to manage this morbid condition.Objectives: To study the various presentations and surgical strategies in treating post-COVID rhino-orbito-cerebral mucormycosis (ROCM).Settings and Design: Observational cross-sectional study.Methods and Materials: From May to October 2021, 270 patients with CAM were admitted to Andhra Medical College Department of Neurosurgery, King George Hospital, Visakhapatnam, India. A cohort of 61 cases with intracranial involvement was studied in detail. The varied presentations and different or innovative treatment modalities were analyzed.Results: The death rate was 30/270 in the whole cohort, and three deaths (4.9%) occurred in 61 cases with cranial involvement. Thirty-three (54.1%) of the 61 cases were treated surgically: 17 patients required bone excision (for focal osteomyelitis) and 16 cases required abscess drainage/excision.Conclusions: Post-COVID mucormycosis (especially with intracranial involvement) is a highly challenging entity. A multidisciplinary approach with early and aggressive anti-fungal medication combined with timely surgical interventions offers some hope of overcoming this complex infection in CAM patients. We identified some novel techniques during regular follow-up that have proven helpful in combatting this devastating condition. [ABSTRACT FROM AUTHOR]

Invasive fungal diseases (IFD) still cause substantial morbidity and mortality, and new therapeutic approaches are urgently needed. Recent data suggest a benefit of checkpoint inhibitors (ICI). We report the case of a diabetic patient with refractory IFD following a SARSCoV-2 infection treated by ICI and interferon-gamma associated with antifungal treatment.

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31st 2018. Data sources included PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients. [ABSTRACT FROM AUTHOR]

Introduction: Mucormycosis are infections caused by molds of the order Mucorales. These opportunistic infections are rare, difficult to diagnose, and have a poor prognosis. We aimed to describe common radiographic patterns that may help to diagnose cerebral mucormycosis and search for histopathological correlations with imaging data. Methods: We studied the radiological findings (CT and MRI) of 18 patients with cerebral mucormycosis and four patients' histopathological findings. Results: All patients were immunocompromised and/or diabetic. The type of lesions depended on the infection's dissemination pathway. Hematogenous dissemination lesions were most frequently abscesses (59 lesions), cortical, cortical–subcortical, or in the basal ganglia, with a halo aspect on DWI for lesions larger than 1.6 cm. Only seven lesions were enhanced after contrast injection, with different presentations depending on patients' immune status. Ischemia and hemorrhagic areas were also seen. Vascular lesions were represented by stenosis and thrombosis. Direct posterior extension lesions were bi-fronto basal hypodensities on CT and restricted diffusion without enhancement on MRI. A particular extension, perineural spread, was seen along the trigeminal nerve. Histopathological analysis found endovascular lesions with destruction of vessel walls by Mucorales, microbleeds around vessels, as well as acute and chronic inflammation. Conclusions: MRI is the critical exam for cerebral mucormycosis. Weak ring enhancement and reduced halo diffusion suggest the diagnosis of fungal infections. Involvement of the frontal lobes should raise suspicion of mucormycosis (along with aspergillosis). The perineural spread can be considered a more specific extension pathway of mucormycosis. [ABSTRACT FROM AUTHOR]

Introduction: Invasive fungal infections are a primary cause of morbidity and mortality in patients with haematological malignancies., Case Presentation: We describe an unusual clinical and radiological presentation of invasive mucormycosis (IM) in a 69-year-old patient with relapsed acute myeloid leukaemia. The patient was diagnosed with disseminated IM with involvement of the central nervous system in an atypical location, lung, spleen, muscle, bone, and heart, after having completed induction and bridging chemotherapy to allogeneic haematopoietic stem cell transplant (HSCT). Her clinical presentation was atypical with mild neurological symptoms slowly progressing over 2 months and without appropriate signs of systemic inflammation. Mucorales was eventually confirmed from bronchoalveolar lavage and subdural collection., Conclusion: This report highlights the difficult challenges of managing disseminated IM in an immunocompromised patient, where close multidisciplinary specialist care enabled successful treatment, followed by T-cell-depleted allogeneic HSCT for a high-risk haematological malignancy., (© 2024 S. Karger AG, Basel.)

Patients with diabetes are considered a high‐risk group involved with cerebral mucormycosis (CM). Due to the potential of Mucorales to invade sinuses and its rapid progression into orbit and retro‐orbital areas and even brain, in most cases, CM is fatal in patients with diabetes. In the last few decades, mucormycosis and background conditions responsible for the development of its infections have received a great deal of attention. Dysfunction of innate and adaptive immune system, the increased amount of available nutrition, expression of host factors, and free iron level in plasma in diabetic ketoacidosis are among the topics that have been mostly taken into account so far. Therefore, it is important to clarify the molecular mechanisms that let the Mucorales to involve the patients with diabetes, which even at early stages of diagnosis and treatment, there is minimum chance to control the disease. [ABSTRACT FROM AUTHOR]

As cerebral mucormycosis is devastating in nature, here we discuss possible use of the intranasal route, in comparison to or in addition to intravenous administration, as a therapeutic approach to manage cases of mucormycosis with central nervous system involvement. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with diabetes are known as an important high‐risk group for cerebral mucormycosis (CM). Method: We conducted a structured search using PubMed/MEDLINE to collect both case reports and case series case (ie including at least two patients) onto CM in diabetic patient published between 2000 and March 2020. Results: Forty‐five reports of individual cases and eighteen case series articles were included. India accounted for the largest share of reports with 37.7% and 38.8% of individual cases and case series, respectively. Mortality ranged from 0% to 100% in the case series. The overall mortality in the individual cases was 46.3%, and 64.2% of deaths were reported in patients with ketoacidosis diabetes. Facial swelling (53.3%), headache (44.4%), loss of vision (35.5%) and ophthalmoplegia (35.5%) were the most frequently reported clinical symptoms. In all patients except 4 (91.1%), CM was treated surgically; however, in many cases (42%), despite the use of surgery, death occurred. Amphotericin B deoxycholate (AMB) and lipid‐based AMB (LAMB) were used as the first lines of treatment for all patients; however, posaconazole, echinocandins, hyperbaric oxygen therapy (HBOT) and deferasirox were used in combination for a number of patients. Posaconazole has been shown to have positive therapeutic effect; however, posaconazole, LAMB and HBOT are not commonly used in low‐income and health‐challenged countries. Conclusion: Cerebral mucormycosis is a rapidly progressive infection in diabetic patients and carries immense morbidity despite early diagnosis and treatment. Low‐income countries have had the highest number of reports of the disease in recent years, indicating the need to control diabetes in these countries. [ABSTRACT FROM AUTHOR]

Isolated cerebral mucormycosis can be life-threatening in immunocompromised patients. Sinus and lung were the most involved organs, while cerebral infection by mucormycosis is more fetal. This infection needs proper debridement and antifungal therapy. We report a 12-year-old diabetic girl with manifestations of fever, headache, and weakness in the right upper and lower extremities without any involvement of sinuses and lung. The patient had approximately normal routine laboratory data, and its CSF was not diagnostic. Because of its features in brain CT and MRI that suggested a necrotic lesion in the left parietal lobe, she was undergone craniotomy and received broad-spectrum antibiotics along with anti-fungal and anti-tuberculosis drugs. Histopathological findings of the mass, which was excised in craniotomy, confirmed the diagnosis of mucormycosis. Unfortunately, the patient died because of this invasive infection. The fatality of fungal infections, especially cerebral types, warn us to be aware of them in immunocompromised patients and perform the proper treatment to reduce its mortality.

Abstract We report on an elderly male patient with headache and right-side weakness. Imaging studies revealed multiple space-occupying lesions in the parietal and occipital cerebral regions. Biopsy revealed broad aseptate ribbon-like structures branching at right angles, suggestive of mucormycosis. Improvement was observed after medical therapy with 20 weeks of liposomal amphotericin B (5 mg/kg/day) combined with posaconazole, followed by posaconazole (400 mg twice a day) alone for 1 month. The patient recovered without neurological deficits; however, multidrug-resistant bacteraemia and hospital-acquired pneumonia occurred, resulting in death. Nevertheless, our report shows that this lethal fungal infection can sometimes show favourable progress with drug therapy alone. [ABSTRACT FROM AUTHOR]

Isolated Infection of central nervous system by the family Mucoraceae is a rare but life-threatening infection. We present a case of isolated cerebral mucormycosis in a 53-year-old immunocompetent woman without any rhinoorbital focus. She underwent excision biopsy followed by treatment with amphotericin B, resulting in resolution of symptoms clinically and the lesion radiologically. [ABSTRACT FROM AUTHOR]

This review focuses on sinus, sino-orbital, and rhinocerebral infection caused by the Mucorales. As the traditional term of 'rhinocerebral' mucormycosis omits the critical involvement of the eye, the more comprehensive term as rhino-orbital-cerebral mucormycosis (ROCM) is used. The most common underlying illnesses of ROCM are diabetes mellitus, hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. Sporangiospores are deposited in the nasal turbinates and paranasal sinuses in immunocompromised patients. Qualitative and quantitative abnormalities of neutrophils, monocytes and macrophages increase the risk for development of mucormycosis. Altered iron metabolism also is a critical factor in the pathogenesis of patients with diabetes mellitus who are at risk for ROCM. Angioinvasion with thrombosis and tissue necrosis is a key pathophysiological feature of human Mucorales infection. The ethmoid sinus is a critical site from which sinus mucormycosis may extend through the lamina papyracea into the orbit, extraocular muscles, and optic nerve. The brain may be seeded by invasion of the ethmoidal and orbital veins, which drain into the cavernous sinuses. Diplopia and ophthalmoplegia may be the earliest manifestations of cavernous sinus syndrome before changes are apparent on diagnostic imaging modalities. Negative diagnostic imaging does not exclude cavernous sinus mucormycosis. Mucormycosis of the maxillary sinus has a constellation of clinical features that are different from that of ethmoid sinus mucormycosis. A painful black necrotic ulceration may develop on the hard palate, indicating extension from the maxillary sinus into the oral cavity. Orbital apex syndrome is an ominous complication of mucormycosis of the orbit. Once within the orbital compartment, organisms may extend posteriorly to the optic foramen, where the ophthalmic artery, ophthalmic nerve and optic nerve are threatened by invasion, edema, inflammation and necrosis. Early diagnosis of sinus mucormycosis is critical for prevention of extension to orbital and cerebral tissues. Optimal therapy requires a multidisciplinary approach that relies on prompt institution of appropriate antifungal therapy with amphotericin B, reversal of underlying predisposing conditions, and, where possible, surgical debridement of devitalized tissue. Outcomes are highly dependent upon the degree of immunosuppression, site and extent of infection, timeliness of therapy, and type of treatment provided. New modalities for early diagnosis and therapeutic intervention are critically needed for improved outcome of patients with ROCM. [ABSTRACT FROM AUTHOR]

Abstract: Rhinocerebral mucormycosis is an acute, fulminating form of invasive fungal sinusitis occurring principally in individuals who are immunologically or metabolically compromised. The incidence of pituitary apoplexy ranges from 6% to 17%, presenting as a capsule rupture in up to 1.7–2.0%. Isolated cases of mucormycosis are associated with solid tumors and Cushing’s syndrome. A 42-year-old, diabetic woman, with Cushing’s syndrome of 5 years duration presented with hemiplexy, hemiparesis and altered speech following a syncopal episode and fall. Brain CT scan showed a left temporal lobe infarction. The patient deteriorated rapidly and she died 4 days later. Autopsy findings included: plurihormonal pituitary adenoma with extension to the sphenoid bone and sellar erosion; many thick, septated, mucormycosis hyphae; and recent fronto-temporal brain infarction. Also, a solitary adrenal corticotropic hormone (ACTH)-producing neuroendocrine tumor, 3 cm in diameter, was found in the left lung. This patient illustrates the correlation between ACTH-producing ectopic pulmonary tumor, pituitary apoplexy and mucormycosis. [Copyright &y& Elsevier]

Background Isolated cerebral mucormycosis is a rare and serious infection associated with intravenous drug abuse. Methods We performed a comprehensive meta-analysis of cases reported in studies and have included an unreported case from our institution. We searched PubMed/Medline, EMBASE, Scopus, Cochrane Databases, and our institution's electronic medical health records from inception through March 31, 2018. The cases were considered isolated (only affecting the cerebrum, cerebellum, or brainstem) if the absence of other primary sources of infection had been documented. Continuous variables were summarized using the median and interquartile range and categorical variables using frequencies and proportions. The relationships between variables were tested using the Wilcoxon rank sum and Pearson χ2 tests. Results A total of 130 studies (141 patients) met the eligibility requirements and were screened; 68 patients were included. The median age was 28 years (interquartile range, 24–38); 57% were men. Most patients had a history of intravenous drug abuse (82%), and 20% had positive human immunodeficiency virus findings. The lesion location was mostly supratentorial (91%), especially in the basal ganglia (71.2%). The cultures were positive in 38%, with Rhizopus the most common organism (59%). The mortality rate was 65%. The survivors were significantly more likely to have received amphotericin B (92% vs. 43%; P < 0.001) or to have undergone stereotactic aspiration (58% vs. 25%; P < 0.01). Conclusions Isolated cerebral mucormycosis has a pooled mortality rate of 65%. The presence of lesions in the basal ganglia, rapidly progressive symptoms, and a history of intravenous drug abuse should raise suspicion for the early initiation of amphotericin B and stereotactic aspiration. [ABSTRACT FROM AUTHOR]