Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

Mucormycosis during COVID-19 era: A retrospective assessment.

In a retrospective view, this review examines the impact of mucormycosis on health workers and researchers during the COVID era. The diagnostic and treatment challenges arising from unestablished underlying pathology and limited case studies add strain to healthcare systems. Mucormycosis, caused by environmental molds, poses a significant threat to COVID-19 patients, particularly those with comorbidities and compromised immune systems. Due to a variety of infectious Mucorales causes and regionally related risk factors, the disease's incidence is rising globally. Data on mucormycosis remains scarce in many countries, highlighting the urgent need for more extensive research on its epidemiology and prevalence. This review explores the associations between COVID-19 disease and mucormycosis pathology, shedding light on potential future diagnostic techniques based on the fungal agent's biochemical components. Medications used in ICUs and for life support in ventilated patients have been reported, revealing the challenge of managing this dual onslaught. To develop more effective treatment strategies, it is crucial to identify novel pharmacological targets through "pragmatic" multicenter trials and registries. In the absence of positive mycology culture data, early clinical detection, prompt treatment, and tissue biopsy are essential to confirm the specific morphologic features of the fungal agent. This review delves into the history, pathogens, and pathogenesis of mucormycosis, its opportunistic nature in COVID or immunocompromised individuals, and the latest advancements in therapeutics. Additionally, it offers a forward-looking perspective on potential pharmacological targets for future drug development.

Diagnosis of mucormycosis from nasal swabs using commercial PCR platforms; a feasible alternative?

Rhino-orbital-cerebral mucormycosis (ROCM) is linked to uncontrolled diabetes, diabetic ketoacidosis, iron overload, corticosteroid therapy, and neutropenia. This study evaluated a commercial real-time PCR system's effectiveness in detecting Mucorales from nasal swabs in 50 high-risk patients. Nasal swab PCR showed 30% positivity, compared to 8% with KOH microscopy. Despite its improved sensitivity, nasal swab PCR has limitations, highlighting the importance of established sampling methods in mucormycosis diagnosis. Participants were predominantly male (64%), with diabetes (78%) and amphotericin B use (96%). Prior COVID-19 was 42%, with 30% positive for Mucorales by PCR, compared to 8% with KOH microscopy.

Resurgence of orbital mucormycosis during COVID-19 pandemic: Study from a tertiary care center in Eastern India.

PURPOSE: A sudden surge of Mucormycosis cases during the second wave of Covid 19 was observed in certain parts of India. The reasons for this upsurge remain unknown. However its impact on the overall healthcare system was quite overwhelming. In this context this study was decided to estimate and assess the spectrum of orbital involvement in patients with Mucormycosis, to find its association with coexisting disease entities if any, and at the same time evaluate the therapeutic response to established treatment regimens. MATERIALS AND METHODS: This descriptive longitudinal study was conducted over a period of six months. Patients presenting with symptoms of Mucormycosis were jointly evaluated by a multi speciality team. After confirmation of diagnosis, patients were treated with intravenous Amphotericin B, surgical debridement of affected sinuses and orbital exenteration when indicated. They were followed up for three months after discharge. RESULTS: Forty-three patients were enrolled in this study. Thirty-seven (86.04%) were COVID positive. All of them had history of steroid exposure during COVID treatment. Ninety five percent of study participants had diabetes mellitus. Twenty-seven (62.79%) patients had orbital involvement. Most common clinical presentation was peri-orbital or facial pain and edema. Besides medical treatment, thirty-nine patients (90.69%) required sinus debridement and nine patients (20.9%) required orbital exenteration. Thirteen patients (30.23%) expired during the follow up period. With treatment disease regressed in twenty patients (46.51%). CONCLUSION: Diabetes and use of steroids to prevent anticipated cytokine storm may be the inciting factors for Orbital Mucormycosis in COVID patients. Early diagnosis, treatment and control of risk factors are keys for recovery and survival..

Rehabilitation of the Surgical Defect Secondary to Mucormycosis With a Definitive Obturator: A Case Report.

Neglect initially starts as an infection, evolving into a disease. During the COVID-19 pandemic, lifestyle changes and disturbed food intake have weakened immune systems, making individuals more susceptible to secondary infections. Mucormycosis poses a significant threat, especially during the COVID-19 pandemic when immune systems may be compromised. The impact of the disease extends beyond physical health, affecting psychological and social well-being due to the challenges, such as difficulties in mastication, speech, and swallowing post-surgery. The mention of maxillectomy highlights the severe nature of some cases, necessitating surgical intervention to remove the affected tissue. Anatomical and functional losses following surgical excision of the maxilla and surrounding tissues need to be recovered as soon as possible. After surgery, prostheses can and should be used to restore speech, mastication, and deglutition - three essential physiological activities. Thus, a patient's treatment approach should include prosthetic planning before surgical intervention and rehabilitation after the surgery. If they are carefully handled at the moment of surgery, the overall continuity created by maxilla resection includes at least the oral, nasal, and maxillary sinus cavities, which may prove to be a useful future location for prosthesis retention. As a result, the prosthodontist's role becomes crucial in assisting the surgeon in taking all necessary precautions that are beneficial to the patient.

Idiopathic aplastic anemia with concurrent complications of colonic perforation and mucormycosis: Case report.

We report a case of a 72-year-old female who presented with fever, abdominal pain, and diarrhea accompanied by leukopenia, anemia, and thrombocytopenia. The diagnosis of acute aplastic anemia was confirmed through bone marrow aspiration. Treatment included glucocorticoids, immunoglobulin therapy, and plasma exchange. Subsequently, the patient developed gastrointestinal bleeding and abdominal Computed Tomography (CT) revealed perforation of the transverse colon. Pathological examination of surgically removed diseased tissue confirmed mucor infection. Despite receiving antifungal therapy with amphotericin B, the patient's condition deteriorated due to the sepsis progression. Mucor infection in immunocompromised patients should be vigilant, and early diagnosis may help improve prognosis.

Exploring the feasibility of utilizing universal primers in detecting mucormycosis pathogens: An in-silico analysis.

This study aimed to design and evaluate a universal primer for Polymerase Chain Reaction (PCR)- based detection of mucormycosis-causing fungi by targeting their Internal Transcribed Spacer (ITS) sequences. In-silico analysis was conducted to assess primer suitability. Using Clustal Omega and Primer-BLAST, ITS sequences of 32 fungi species causing mucormycosis were aligned and subjected to primer design. Generated primers were sorted and in silico PCR simulations were performed to identify primers capable of amplifying all fungal species. Instead of identifying one pair of universal primer, in silico PCR analysis identified a panel of 14 primer pairs designed from full-length ITS sequences, and a panel of 12 primer pairs designed from conserved regions, that could detect 31 species. The study recommends a panel of 12 primers for multiplex-PCR to detect mucormycosis-causing fungi instead of a long list of PCR analyses for each fungus in diagnosing mucormycosis.

Number of sinus procedures reduces inpatient mortality for invasive fungal rhinosinusitis.

OBJECTIVES: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. RESULTS: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. CONCLUSION: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.

The Comprehensive Management of Patients with Rhino-Orbito-Cerebral Mucormycosis; A Perspective from Antifungal Treatment to Prosthetic Rehabilitation: A Descriptive Cohort Study.

Surgical intervention is a key element in the management of patients diagnosed with mucormycosis. A retrospective cohort study was carried out, in which patients with a proven diagnosis of mucormycosis were evaluated over a period of 10 years, according to the MSGERC criteria. A descriptive analysis of the clinical characteristics, comorbidities, imaging, and microbiology studies, as well as medical and surgical treatment and the type of prosthesis was carried out. A total of 22 cases were identified, of which 54.5% (n = 12) of the population were men. Furthermore, 77.2% (n = 17) of the population had diabetes mellitus. The main antifungal treatment implemented was liposomal amphotericin B (77.2%, n = 17). The most affected structures in our patients were the paranasal sinuses (n = 18; 81%), followed by the maxilla and orbit (n = 15; 68%), nose (n = 12; 54%), central nervous system (n = 11; 50%), and skin and soft tissues (n = 2; <1%). Of the total population, 59.09% (n = 13) of patients underwent maxillofacial surgery, of which 61.53% (n = 8) required some type of prosthetic rehabilitation. Orbital exenteration and maxillectomy were the most frequent surgeries, accounting for 69.23% (n = 9), while skull base drainage was performed in four patients (30.76%). Of the total number of patients (n = 22), eight died (36.36%). Appropriate surgical management according to the affected structures, considering not only increasing the patient's survival, but also considering the aesthetic and functional consequences, will require subsequent rehabilitation.

A Rare Case of Maxillary Mucormycosis in a Child With Juvenile Diabetes Mellitus.

Mucor and Rhizopus species are recognized as the primary culprits responsible for mucormycosis, a severe fungal infection known for its opportunistic nature. This infection primarily targets individuals with compromised immune systems, including those with diabetes mellitus and patients undergoing glucocorticoid therapy, where the immune response is weakened. This article aims to underscore the pivotal role of prompt diagnosis and intensive treatment in managing mucormycosis, particularly in pediatric patients, as it can avert death and mitigate serious morbidity. This case report emphasizes the urgency of identifying fungal infections in patients with diabetes early on and subsequently treating them aggressively to prevent adverse outcomes. It highlights the potential for excellent treatment outcomes when mucormycosis is promptly diagnosed and managed with intensive therapy. By doing so, significant morbidity and mortality associated with this condition can be effectively prevented, underscoring the importance of vigilance and proactive management in patients with predisposing factors for fungal infections.

Mucormycosis, the Black Fungus in the Post-COVID-19 Pandemic: A Case Report with Review of Literature.

Mucormycosis, a concerning and often fatal fungal infection, has shown a significant rise in cases following the COVID-19 pandemic in India, particularly affecting patients with uncontrolled comorbidities such as diabetes mellitus and other immunocompromised individuals. Our case series examines five instances of mucormycosis, supported by appropriate radiographic and histopathological evidence correlating with clinical observations. Our review indicated that patients were experiencing ailments or undergoing treatments that compromised their immune systems. We analyzed additional epidemiological data, including common infection sites, gender predispositions, and mortality rates. Treatments were tailored based on symptom severity, encompassing both surgical and medical approaches. The primary reason for the rise in cases was linked to elevated glycaemic levels and weakened immunity among post-COVID-19 patients. The report provides a detailed explanation of the factors contributing to this correlation. Our findings underscore the critical importance of timely surgical intervention and advocate for further investigation into treatment efficacy and symptom monitoring specific to mucormycosis in post-COVID-19 patients in India.

Mucor germinans, a novel dimorphic species resembling Paracoccidioides in a clinical sample: questions on ecological strategy.

Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous Mucorales. Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as Mucor germinans sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains Mucor circinelloides and Mucor kunryangriensis as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells in vitro. Multilateral yeast cells emerge in all three Mucor species at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of Paracoccidioides. The ecological role of yeast forms in Mucorales is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for Candida or Paracoccidioides. We demonstrate that the dimorphic transition is common in Mucor species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.

A rare case of pulmonary mucormycosis and broncho-esophageal fistula in a patient with poorly controlled diabetes.

Key Clinical Message: In patients with poorly controlled diabetes, early recognition of rare fungal infections like pulmonary mucormycosis, especially when presenting with unusual complications such as broncho-esophageal fistula, is critical. Prompt intervention with antifungal therapy and consideration for surgical debridement significantly impact outcomes. Multidisciplinary management is paramount for such complex cases. Abstract: Mucormycosis is a rare fungal infection caused by the Mucorales. This infection is mostly observed among those with poorly controlled diabetes or immunodeficiency. The most common presentation of the infection among those with poorly controlled diabetes is rhino-orbit-cerebral involvement. In this case report, we provide the history and outcome of a rare case of pulmonary mucormycosis in a patient with poorly controlled diabetes who was simultaneously diagnosed with broncho-esophageal fistula. Our patient was a 32-year-old male with a history of poorly controlled diabetes. Over the months, he had complained of productive coughs and dyspnea, which had lately been joined by dysphagia. He also claimed to have lost considerable weight (10 kg) during the previous 3 months. Barium swallow showed an abnormal flow of contrast between the bronchus and esophagus, suggesting a broncho-esophageal fistula. Computed tomography of the thorax revealed a broncho-esophageal fistula between the left main bronchus (LMB) and esophagus. He had a bronchoscopy the next day, which revealed necrosis and a broncho-esophageal fistula in the LMB. A bronchial biopsy showed typical hyphae with necrotic tissue, indicating mucormycosis. The patient's antimycotic medication (liposomal amphotericin) was started and a prompt surgery consult was ordered. The patient, however, passed away from massive hemoptysis. We described a rare case of pulmonary mucormycosis with broncho-esophageal fistula in a patient with poorly controlled diabetes. The rarity of this combination highlights the associated diagnostic and treatment hurdles. Early detection, antifungal medication, as soon as possible surgical debridement of involved tissues, and a multidisciplinary approach could improve patient outcomes.

Secondary bacterial infections in post-COVID-19 mucormycosis cases: a retrospective study at Imam Khomeini Hospital Complex, March 2020-April 2021.

Background and Objectives: To explore the prevalence and characteristics of secondary bacterial infections among patients suffering from mucormycosis following COVID-19 infection. Materials and Methods: We conducted a cross-sectional, retrospective analysis from March 2020 to April 2022 at Imam Khomeini Hospital Complex in Tehran. The study included patients with histopathologically confirmed mucormycosis and documented secondary bacterial infections. We extracted and analyzed data from hospital records using SPSS software, version 26. Results: The study comprised 27 patients, with a predominance of females (70.4%) and an average age of 56 years. The majority of these patients (63%) had pre-existing diabetes mellitus. The severity of their COVID-19 infections varied. Treatment regimens included immunosuppressive drugs and antibiotics. Rhinocerebral mucormycosis was the most common form observed. The predominant secondary infections involved the urinary tract, respiratory system, bloodstream (bacteremia), and soft tissues, with resistant strains of Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae being the most frequently identified microorganisms. Notably, cases of bacteremia and pneumonia exhibited a higher mortality rate. Ultimately, 55.6% of patients were discharged, while 44.4% succumbed to their infections. Conclusion: Patients recovering from COVID-19 with mucormycosis are significantly susceptible to secondary bacterial infections, particularly those with diabetes mellitus or those undergoing immunosuppressive therapy. Such infections compound the morbidity and mortality risks in this vulnerable patient cohort.

Cerebritis, optic ischemia, and cavernous sinus thrombosis arising from sinonasal mucormycosis.

Brain and ocular infections can be the worst and fatal consequences of sinonasal infections in immunomodulated or immunocompromised patients. We report a case of a 35-year-old female who received an allogenic hematopoietic stem cell transplantation for acute myeloid leukemia, suffering from maxillo-spheno-ethmoidal rhinosinusitis which was complicated by cavernous sinus thrombosis, orbital cellulitis, optic ischemia and cerebritis.

Case report: Disseminated mucormycosis misdiagnosed as malignancy developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus following SARS-CoV-2 infection in a woman.

Mucormycosis has become more prevalent during the COVID-19 pandemic and is associated with a high mortality rate. However, concurrent host allergic reactions, invasive pulmonary mucormycosis, and disseminated mucormycosis are rarely reported. Herein, we describe a case of disseminated mucormycosis initially misdiagnosed as a malignancy that developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus in a woman with post-SARS-CoV-2 infection. The previously healthy patient presented with a sizeable mass in the right middle lobe and multiple lesions across the lungs, brain, spleen, kidneys, pancreas, and subcutaneous tissue 6 months after SARS-CoV-2 infection, mimicking an extensive metastatic malignancy. Eosinophilia, elevated total plasma immunoglobulin E, and significant eosinophilic lung tissue infiltration were observed. Rhizopus microsporus was isolated from subcutaneous tissue, and hyphae were detected in the lung tissue. Sequential amphotericin B liposomes followed by isavuconazole antifungal therapy combined with systemic corticosteroids improved symptoms, significantly reduced the sizes of pulmonary lesions, and reduced eosinophil count. However, it failed to halt the overall progression of the disease, and the patient died. The absence of asthma-like symptoms and delayed recognition of invasive fungal infection signs contributed to poorer outcomes, highlighting the need for a thorough post-COVID-19 follow-up.

COVID-19-associated rhino-orbito-cerebral mucormycosis: a single center prospective study of 264 patients.

PURPOSE: Outbreaks of mucormycosis were reported worldwide throughout the COVID-19 pandemic. We report clinical outcomes of a treatment protocol for COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM). METHODS: Patients with biopsy-proven mucormycosis and COVID-19 were included. All received intravenous amphotericin B deoxycholate 1 mg/kg and surgical endoscopic sinus debridement (FESS). Those with rhino-orbital or cerebral disease limited to the cavernous sinus were eligible for transcutaneous retrobulbar amphotericin B (TRAMB). Patients were followed with weekly imaging, endoscopic examinations, and serial debridement as necessary. Patients were discharged on oral posaconazole for 6 months. RESULTS: In total, 264 patients were followed for a mean of 2.5 months. On presentation, 163 patients (174 eyes) had eye involvement. Of these, 141 eyes (81.0%) had light perception or worse vision. By the last follow-up, 163 patients (176 eyes) were affected, and of these, 96 eyes (54.5%) had no light perception. Twenty-one patients (8%) died and 3 orbits (0.5%) were exenterated. There was no change in mortality (p = 0.38) or exenteration (p = 0.38) in the 55 patients who received TRAMB compared to patients with rhino-orbital or cerebral disease limited to the cavernous sinus who did not. Asymptomatic COVID-19 was associated with higher mortality than symptomatic COVID-19 (p = 0.025). Uncontrolled diabetes was a risk factor for death (p = 0.022). New diabetes was associated with increased mortality versus pre-existing diabetes (p = 0.005). CONCLUSION: A multidisciplinary approach is crucial to manage COVID-19-ROCM. In our cohort, TRAMB therapy did not increase mortality or exenteration rates. While poor vision on presentation was profound, some vision recovery was noted with treatment. COVID-19 immune dysregulation may predispose patients to ROCM, particularly those with asymptomatic disease.

Maxillary Mucormycotic Osteonecrosis as a Manifestation of Post-COVID-19 Infection in Non-diabetic Patients: Report of Two Cases.

Mucormycosis is a rare, opportunistic fungal infection prevalent in the elderly, especially in patients with uncontrolled diabetes or a compromised immune system. However, the outbreak of the pandemic declared by the World Health Organization in late 2019 increased the incidence of mucormycosis cases in COVID-19 patients due to increased steroid usage that resulted in an immunocompromised state. The current report presents two cases of oral mucormycotic osteomyelitis in patients who developed diabetes post-COVID infection, along with a review and relevant literature.

Successful Treatment of Sternal Osteomyelitis and Mediastinitis Caused by Rhizopus Following Cardiac Surgery.

Sternal osteomyelitis and mediastinitis are rare yet severe complications post-cardiac surgery, often associated with significant morbidity and mortality. Fungal etiologies, particularly those caused by Rhizopus spp., are infrequent but can lead to aggressive infections. Here, we present the case of a 68-year-old male who developed sternal osteomyelitis and mediastinitis caused by Rhizopus spp. two weeks following coronary artery bypass grafting surgery. Debridement and pectoralis flap reconstruction were performed following clinical identification and confirmation with microbiological examinations and a CT scan. Prompt recognition, aggressive surgical intervention, and targeted antifungal therapy were crucial for successful management. This case underscores the importance of considering fungal pathogens, such as Rhizopus, in the differential diagnosis of post-cardiac surgery infections, as well as aggressive treatment to improve outcomes for affected patients.

Primary renal mucormycosis in a type 2 diabetic patient: A case report from Syria.

Mucormycosis is an opportunistic fungal infection that primarily affects immunocompromised individuals and rarely presents as renal mucormycosis (RM). Diagnosis can be challenging for many physicians. We report a rare case of primary, unilateral RM which triggered diabetic ketoacidosis in a type 2 diabetic patient. The case was later complicated by a bronchopleural fistula and a meropenem-resistant Klebsiella infection. The patient was ultimately treated with surgical intervention, liposomal amphotericin B, and polymyxine E. Early diagnosis and timely treatment of this life-threatening disease and its complications are significant in reducing mortality.