Rhinocerebral Zygomycosis Research Articles

Treating patients with deep mycoses of the maxillofacial region against a COVID-19 background

BACKGROUND: Complications characterized by necrosis of the nasal mucosa and the hard palate, as well as the middle and lower nasal concha with exposure of the alveolar process, destruction of the posterior wall of the maxillary sinus and the bottom of the orbit caused by a fungal infection were noted during the COVID-19 pandemic. By January 2022, such cases had been documented in 18 countries worldwide. The main predisposing factors for this condition are diabetes mellitus and inadequate use of corticosteroids. Rhinocerebral mucormycosis or zygomycosis is a rare disease caused by filamentous fungi affecting the nose, paranasal sinuses, and brain.
 AIM: To present the treatment strategy for patients with deep mycoses of the maxillofacial region against a background of transferred COVID-19 in the State Clinical Hospital named after F.I. Inozemtsev DZM.
 MATERIAL AND METHODS: Fifteen patients with a cerebral form of mucormycosis of the maxillofacial region arose against a background of a new coronavirus infection associated with SARS-CoV-2.
 RESULTS: The study shows the importance of timely initiation of radical surgical treatment for the rhinocerebral form of mucormycosis in the maxillofacial region, which arose against the background of SARS-CoV-2, to prevent the spread of osteomyelitic foci in bone tissue.
 CONCLUSION: Early diagnosis of mucormycosis, timely treatment with antipsychotic medications and surgical intervention, control of the level of glycemia, and reasonable use of corticosteroids prevented the development of complications.

Rhinocerebral Form of Invasive Mycosis in COVID-19 Patients: Clinical Course, Diagnosis, Treatment Experience

Background. The incidence of invasive mycoses is reported to increase among patients with a history of new coronavirus infection COVID-19. Adhesion and damage of endothelial cells by zygomycetes lead to fungus angioinvasion, release of a large number of fungal proteases, lipases and mycotoxins, as well as vascular thrombosis, subsequent necrosis of tissues.Objectives. Improvement of the diagnosis and treatment for COVID-19 associated invasive mycosis.Methods. Examination and treatment of 143 patients with invasive mycosis of the maxillofacial area in the period from August 2021 to May 2022 at the Maxillofacial Unit of Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, Russia. The diagnosis was confi rmed by cytological, culture-based methods, as well as pathomorphological study of surgical specimen. Follow-up monitoring was carried out in 1, 3, 6 months, with repeated CT and MRI investigations. The group under follow-up monitoring included 91 patients. The incidence of signs was determined via descriptive statistics methods in proportion of the total number of observations and expressed as a percentage. Statistika 12.5 and Excel 2010 (Windows 10) were used in the study, the graphical representation of the material was made in the same programs.Results. Manifestation of invasive mycoses of the maxillofacial area occurred during the early convalescent period of coronavirus infection in specialized infectious hospitals or within two weeks after discharge from the hospital. A typical clinical picture includes rhinocerebral zygomycosis with the development of fungal osteomyelitis of the upper jaw, nasal bones, zygomatic bone, ethmoidal labyrinth bones, sphenoid bone, frontal bone. 17 cases (11.9%) had a lethal outcome as a result of disseminated form of fungal infection caused by Mucorales (14 patients), Aspergillus (3 patients) with damage to the brain, lungs, kidneys and fatal massive necrotic lesions of the craniofacial area. An integrated approach embraced early antifungal therapy (Amphotericin B) as well as surgical debridement of the lesions and provided a positive effect in treatment.Conclusion. Invasive fungal infections require prompt diagnosis and early prescription of antifungal therapy (prior to histological confi rmation of diagnosis) to minimize consequences and prevent fatal outcome. Due to the nonspecifi c nature of clinical symptoms and diffi culties of early diagnosis of invasive zygomycosis and aspergillosis, it is necessary to be alert to potential invasive aggressive mycoses in immunocompromised patients who have a history of a new coronavirus infection COVID-19.

Profile of Secondary Bacterial and Fungal Infections in Hospitalized COVID-19 Patients in a Tertiary Care Centre.

IntroductionSARS CoV-2, a novel corona virus, has emerged in December 2019. The COVID-19 associated mortality is documented in elderly with co morbidities. To have better insight on this issue, the secondary bacterial infections with multi-drug-resistant bacteria in COVID-19 patients need to be studied to evaluate the impact of these infections on the outcome.Aim and objectivesTo determine the proportion of secondary infections in COVID-19 patients. To study the spectrum of pathogens and antibiogram of the bacteria isolated from secondary infections in such patients. To evaluate the co-existing co-morbidities, treatment and outcome in these patients.MethodologyThe retrospective study was conducted in Departments of Medicine and Microbiology, KMC hospitals Attavara and Ambedkar circle, Mangaluru, including all the hospitalized microbiologically confirmed cases of SARS CoV-2 infection. Details pertaining to the study population were collected using a structured proforma. Descriptive data were entered in the form of mean, median and proportions. The categorical values were analyzed using Chi square test. Values of p < 0.05 were considered as statistically significant.ResultsTwo hundred COVID-19 hospitalized patients were included.28 out of 200 patients (14%) studied developed secondary infections. The types of secondary infections were Respiratory infections (50%), blood stream infections (17%), UTI (14%), Rhinocerebral Zygomycosis (17%). The predominant organisms were Klebsiella pneumoniae (44%), Zygomycetes (17%). The rates of antibiotic resistance in Gram negative bacilli were 33% to Cefuroxime,25% to aminoglycosides and fluoroquinolones and 16% to carbapenems. The mortality of 42.8% was observed in patients with secondary infections.ConclusionClose monitoring and follow up especially in high-risk group of severe COVID 19 patients is crucial for better management and outcome.

Mucormycosis and Role of COVID-19 in its Pathogenicity in India: A Review

Mucormycosis is a rising cause of invasive fungal infection but difficulty in diagnosis is the biggest detriment to early diagnosis. Rhinocerebral zygomycosis is most prevalent leading to vascular invasion, tissue necrosis, or even death. Rhizopus arrhizus is the most common causative agent of the disease, found on decaying organic matter but disease from Cunninghamella and Rhizomucor species should not be overlooked. The recent outbreak of COVID-19 pandemic has given rise to increasing patients of diabetes mellitus whose post-COVID immunocompromised state coupled with steroid use has led to rising numbers of mucormycosis patients in India. The establishment of a standard for permissible levels of microbial load in indoor environments has been suggested.

Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease

BackgroundThe role of culture-independent techniques (galactomannan, (1-3)-β-d-glucan) in the early diagnosis of invasive fungal diseases (IFD) is well assessed in hematological patients, but there are no clear conclusions in patients with chronic obstructive pulmonary disease (COPD). AimsTo study the usefulness of nonculture-based techniques in the diagnosis of IFD in COPD-patients at risk for IFD. MethodsA prospective observational study based on monitoring COPD patients at risk for IFD during 2007–2010 was carried out. The presence of galactomannan, (1-3)-β-d-glucan and an indirect immunofluorescence of Candida albicans germ tube specific antibodies (CAGTA) were performed. ResultsAmong 43 COPD patients, 16 (37.2%) were diagnosed with IFD: seven cases were proven IFD (five invasive candidemia – IC, one invasive aspergillosis – IA and a rhinocerebral zygomycosis) and nine probable IFD (seven IA and two IC). In the diagnosis of IC and IA, the negative predictive value (NPV) of (1-3)-β-d-glucan was 100%. Regarding CAGTA in IC, NPV was 96.2%. Finally, NPV of galactomannan in IA was 91.2%. The area under the ROC curve for (1-3)-β-d-glucan in IC and for the rest of the IFD cases was 0.86 (95% CI, 0.79–0.93) and 0.60 (95% CI, 0.43–0.77), for CAGTA in IC was 0.83 (95% CI, 0.74–0.91) and for galactomannan in IA was 0.71 (95% CI, 0.56–0.85). Positive (1-3)-β-d-glucan preceded the growth of Candida (average of 1.7 days) in blood culture. ConclusionsIn COPD patients at risk for IFD the assayed techniques are especially useful to rule out the presence of IFD.

Mukormykoza nosowo-mózgowa: obraz kliniczny, diagnostyka, leczenie – przegląd piśmiennictwa

Many pathogens present in the human environment, in immunocompromised patients, can cause extremely severe opportunistic infections. Most patients suffering from immunological disorders are rarely treated at maxillo-facial departments. In some special cases they require a direct clinical approach. Fungal infections in the cranio-facial area do not occur often, as opposed to infections from bacterial flora which are most frequently found. Some special conditions and requirements are needed to be present for the occurrence of fungal infections. If found, many of them are treated locally by antifungal medicaments, while a few of them require additional radical surgical excisional approach. Mucor sp. is one of these infections and it is related with mucormycosis (zygomycosis). Rhinocerebral zygomycosis is particularly dangerous. This rare cranio-facial infection is a great challenge for all clinicians and surgeons. It seems that only an accurate and proper diagnosis has an impact on the patient’s survival and post-treatment quality of life. In this paper we focus on recent clinical findings and treatment methods of this disease.

Survival Without Neurological Impairment of a Patient With Rhino‐Orbito‐Cerebral Zygomycosis

Rhinocerebral zygomycosis is a rare condition characterized by infection initially in the nose and paranasal sinuses with atypical symptoms consistent with sinusitis. Once established in the nasal sinuses, the infection can easily spread to the orbital region and brain. In the localized form of the infection, the mortality rate is approximately 10%, which increases in the occurrence of orbital involvement and survival in patients of cerebral dissemination is extremely rare. The present paper reports a patient of nasal zygomycosis with orbital and cerebral dissemination in an otherwise healthy patient who survived after 14 months of hospitalization with no neurological impairment. A review of the literature addressing aspects related to diagnosis, treatment, and complications of this fungal infection is also presented.

Rhinocerebral zygomycosis: an unusual dramatic presentation in a paediatric cardiac patient without risk factors.

Mucormycosis is an angioinvasive infection caused by ubiquitous filamentous fungi of the order Mucorales. We describe a case of rhinocerebral mucormycosis presented in a paediatric patient after cardiac surgery correction of a complete atrioventricular canal defect. The rhinocerebral form of mucormycosis in our patient presented as an important epistaxis that needed immediate intubation due to blood inhalation. Furthermore, due to the worsening of pulmonary function, the patient also needed mechanical support with veno-arterial extracorporeal membrane oxygenation. The patient died as a consequence of a disseminated form of fungal infection. We describe our experience of this rare opportunistic infection and we think that early recognition of the disease could help in proper management.

Epidemiological aspects and clinical outcome of patients with Rhinocerebral zygomycosis: a survey in a referral hospital in Iran.

IntroductionNo comprehensive reports have been published on epidemiological status of Rhinocerebral zygomycosis infections and its outcome in our population, Hence, the current study came to address epidemiological characteristics as well as clinical outcome of patients with Rhinocerebral zygomycosis infection referred to a referral hospital in Iran.MethodsThis retrospective study was performed at the Rasoul-e-Akram hospital, an 800-bed tertiary care teaching hospital in Tehran, Iran. The pathology recorded charts were reviewed to identify all cases of Rhinocerebral zygomycosis from patients admitted between April 2007 and March 2014. A diagnosis of Rhinocerebral zygomycosis was based on histopathological assessments.ResultsSixty four patients with Rhinocerebral zygomycosis were assessed. The mean age of the patients was 46.07 ± 22.59 years and 51.6% were female. Among those, 67.2% were diabetic, 26.6% were hypertensive and 29.7% had history of cancer. Different sinuses were infected in 73.4% of the patients. Out of all the patients 26.6% underwent surgical procedures and 17.2% were controlled medically. Extensive debridement was carried out in 40.6%. Neutropenia (<1500 cell/ µl) was revealed in 12.5%. In-hospital mortality rate was 35.9% and prolonged hospital stay (> 14 days) was found in 60.9%. According to the Multivariable logistic regression analysis, the main predictors of in-hospital mortality included female gender, advanced age, the presence of sinus infection, and neutropenia, while higher dosages of amphotericin administered had a protective role in preventing early mortality. In a similar Multivariate model, history of cancer could predict prolonged hospital stay, whereas using higher dose of amphotericin could lead to shortening length of hospital stay.ConclusionThere is no difference in demographic characteristics between our patients with Rhinocerebral zygomycosis and other nations. The presence of diabetes mellitus is closely associated with the presence of this infection. Sinus involvement is very common in those with Rhinocerebral zygomycosis leading to high mortality and morbidity. Besides female gender, advanced age, and presence of neutropenia was a major risk factor for increasing early mortality. The use of higher doses of antifungal treatment such as amphotericin can prevent both mortality and prolonged hospital stay. The cancer patients may need longer hospital stay because of needing comprehensive in-hospital treatment.

Evaluation of patients with zygomycosis.

Zygomycosis is a severe angioinvasive infection caused by Zygomycetes. We retrospectively investigated 16 cases of zygomycosis. The data of patients, who had been followed between 2004 and 2010 in 8 tertiary-care teaching hospitals, were reviewed. Demographic characteristics, underlying diseases, and clinical signs and symptoms of the patients, as well as diagnostic methods, data obtained by radiological imaging methods, and the therapies, were recorded. Therapeutic approaches, antifungal agents and duration of use, and the characteristics of the cases were identified. The study included 11 female and 5 male subjects. The most common symptoms and clinical signs were fever (n = 9) and retro- orbital pain (n = 7). Rhinocerebral zygomycosis was the most common form. The mean time elapsed for diagnosis was 14.26 + 13.96 (range: 2-52) days. Antifungal therapy was given to 15 patients (94%). In addition to antifungal therapy, 12 patients underwent surgical intervention 1 to 4 times. The mean duration of receiving antifungal therapy was 61.4 + 58.02 (range: 1-180) days. The median duration of treatment was 62.5 (range: 42-180) days in survivors. Zygomycosis is an infectious disease with high mortality despite antifungal therapy and surgical interventions.

Rhinocerebral zygomycosis with pansinusitis in a 14-year-old girl with type 1 diabetes: a case report and review of the literature

BackgroundZygomycosis is a rare life-threatening fungal infection affecting mostly patients with predisposing conditions such as diabetes mellitus, immunodeficiency, haemochromatosis or major trauma.MethodsWe describe a case of rhinocerebral zygomycosis in a girl with type 1 diabetes and review previous published cases and treatment options.ResultsA 14-year-old girl with type 1 diabetes mellitus occurred with dental pain, facial swelling, ecchymosis and left eye decreased visual acuity, unresponsive to antibiotic therapy. The coltures of the sinusal mucosa were positive for fungal species belonging to the Zygomycetes. She performed antifungal therapy with posaconazole (POS) with a very slow improvement and a poor glycemic control, leading to blindness of the left eye.ConclusionOur report adds further awareness on rhinocerebral zygomycosis and emphasizes on urgent diagnosis and timely management of this potentially fatal fungal infection through an adequate treatment.

Intracranial hypertension: An unusual presentation of mucormycosis in a kidney transplant recipient

Idiopathic intracranial hypertension (IIH), once called pseudotumor cerebri, presents with nonspecific signs and symptoms of increased intracranial pressure and papilledema, and is associated with high risk of loss of vision. Zygomycosis is a rare but serious fungal infection seen occasionally among renal transplant recipients in the late transplant period with high mortality risk. Early diagnosis coupled with multidisciplinary care can salvage the patient from the risk of death. We present an unusual case of adult renal transplant recipient with IIH followed by rhinocerebral zygomycosis secondary to amplified immunosuppression that was managed successfully.

A rare pulmonary zygomycosis manifested as chronic mediastinitis and bronchial perforation

To the Editors: Zygomycosis is an emerging infection caused by fungi of class Zygomycetes, order Mucorales. It occurs mostly in diabetic and immunocompromised patients, but occasionally occurs in immunocompetent individuals [1]. After rhinocerebral zygomycosis, pulmonary zygomycosis, which carries a high mortality rate, is the second most common presentation [1]. Common manifestations of pulmonary zygomycosis mainly include different types of pulmonary infiltrates [2], and other rare manifestations such as endobronchial mass lesions or mediastinitis. However, in the literature, bronchial perforation caused by zygomycetes has not been previously documented. This report presents the case of a diabetic patient infected with Rhizopus sp., which resulted in chronic mediastinitis and bronchial perforation. A 76-yr-old, Chinese, never-smoking female with uncontrolled type 2 diabetes experienced a productive cough for 6 months prior to admission. This patient denied having fever, breathlessness, night sweating or body weight loss. Physical examination revealed a moderately nourished female without respiratory distress or fever. Upon admission, laboratory studies revealed a haemoglobin level of 10.5 g·dL−1, white blood cell count 5.4×103 cells per μL (53.3% neutrophils, 28.3% lymphocytes, 6% monocytes and 12% eosinophils), platelet count 355×103 cells per μL, creatinine 0.9 mg·dL−1, C-reactive protein 1.7 mg·dL−1, fasting glucose level 311 mg·dL−1 and glycated haemoglobin 14.7%. The chest radiograph on admission revealed partial atelectasis of the …

Perineural trigeminal nerve abscess secondary to Mucor sinusitis: Serial diffusion-weighted MRI and literature review

Perineural extension of rhinocerebral zygomycosis is rare. The role of diffusion-weighted imaging (DWI) in perineural extension and abscess formation within the nerve has not yet been reported in the literature. This is the first case report highlighting the role of DWI in the perineural extension of zygomycosis. We discuss the differential diagnosis and review the literature.

Rhinocerebral zygomycosis in a diabetic patient

Rhinocerebral zygomycosis is the most frequent form of fungal infection caused by members of the Zygomycetes class. A fatal case of rhinocerebral zygomycosis caused by Rhizopus (oryzae) arrhizus with histopathological and mycological diagnosis is reported in a diabetic patient.

Case of a diabetic man cured from rhinocerebral zygomycosis

Zygomycosis (mucormycosis) is a rare, highly aggressive opportunistic fungal disease caused by saprophytic fungi, belonging to the division Zygomycota, class Zygomycetes. Patients with immunodeficiency, neutropenia, iron overload, hematological malignancies, as well as diabetics with ketoacidosis are typically affected. Authors describe the case of an eighteen-year old man with poor compliance suffering from diabetes since the age of nine. He was admitted with ketoacidotic somnolence in severe general condition with unilateral periorbital erythematous edema. Though from nasal exudates gained by the fibero-endoscopic sinus surgery Methicillin-resistant Staphylococcus aureus and Pseudomas aeruginosa was cultured, amphotericin-B was administered as the medical history, clinical picture suggested presence of zygomycosis. An invasive infection caused by Rhizopus oryzae was confirmed by histology and microbiology. The combination of antifungal therapy, repeated surgical interventions and granulocyte colony-stimulating factor resulted in good clinical response. Four month after discharge he is alive and doing well.

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.

Mucormycosis complications in systemic lupus erythematosus

This case involved a 75-year-old woman with systemic lupus erythematosus. Two months previously, she had a flare that was treated successfully by increasing the dosages of prednisone and azathioprine. A sudden onset of ocular pain, diplopia, and loss of vision suggestive of optical neuritis or vascular involvement confused the issue, and rhinocerebral zygomycosis was demonstrated later. We review the presentations of this fungal infection in patients with systemic lupus erythematosus with emphasis on its initial features.

Outbreak of Intestinal Infection Due to Rhizopus microsporus

Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 x 10(3) CFU/g of tablet (range, 3.07 x 10(3) to 5.48 x 10(3)) and 3.24 x 10(3) CFU/g of tablet (range, 2.68 x 10(3) to 3.72 x 10(3)), respectively, which were much higher than the mean count of 2 x 10(2) CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50 degrees C. The long holding time of the intermediates during the manufacturing process of allopurinol amplified the fungal load. Microbiological monitoring of drugs manufactured for highly immunosuppressed patients should be considered.

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.