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.

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.

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.

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.

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.

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.

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 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.

Sinus fungal balls caused by Syncephalastrum spp.: 2 clinical cases and literature review.

INTRODUCTION: Syncephalastrum spp. is a mucoral that rarely produces pathology. Fungal balls caused by this genus are infrequent. It requires early diagnosis and treatment to avoid associated morbidity and mortality. METHODS: We describe two clinical cases of sinus fungus balls caused by Syncephalastrum spp. and review the literature. RESULTS: Two patients were treated for sinus fungus balls. When their samples were analysed, the aetiology was determined to be Syncephalastrum spp. A case of pulmonary fungus ball due to Syncephalastrum spp. is described in the literature. All cases, including these described in the present study, had a good evolution after treatment. CONCLUSIONS: Syncephalastrum spp. is a filamentous fungus that should be considered as an aetiology of sinus fungus ball.

Exploring Prevalence Trends of Jaw Bone Pathologies: A Three-Year Institutional Study.

Background Head and neck bone pathologies cover various conditions with diverse causes. Infections like osteomyelitis and dental abscesses can spread to soft tissues and bones, causing tissue death, inflammation, and systemic effects. Benign and malignant tumors can develop from soft tissue, cartilage, or bone, posing challenges for diagnosis and treatment. Studies on their prevalence in local populations are rare, obscuring our understanding of regional health dynamics. Aim In this study, we aimed to assess the prevalence of bone pathologies documented over the last three years from 2021 to 2023. Materials and methods Histopathologically confirmed cases of bone pathologies at Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India, were gathered from the institutional database (DIAS: Dental Information Archiving Software) from January 1, 2021, to December 31, 2023. They were categorized into groups of infectious and inflammatory lesions, fibro-osseous lesions, malignancies originating from bone, malignancies invading bone, and miscellaneous conditions. The data was then compiled into a Google spreadsheet (Google, Inc., Mountain View, USA) for further analysis. Graphs were created to visualize the prevalence of bone pathologies enabling a descriptive exploration of temporal trends. Results A total of 2626 biopsy records were reviewed. Among these, 242 (9.21%) cases of bone-related pathologies were included, and the remaining 2384 (90.79%) entities without any mention of bone were excluded. Overall, considering all three years, 43.8% (100) bone-related lesions were reported in 2021, 30.3% (77) in 2022 and 25.9% (65) in the year 2023. Under each category, infectious and inflammatory lesions for 40.5% (98), fibro-osseous lesions for 14.9% (36), benign lesions for 2.9% (7), malignancies originating from bone for 1.7% (4), malignancies invading bone for 38% (93), and miscellaneous conditions for 1.65% (4) were reported. The highest number of infectious and inflammatory pathologies (53%) were reported in 2021. A steep fall was observed in 2022 and 2023 under the infectious and inflammatory category. The malignancies invading the bone showed almost similar distribution in all three years. Conclusion The observed variations highlight the unpredictability of bone pathologies, involving the jaw bones. We emphasize continuous observation and analysis to comprehend changing patterns in bone health.

Epidemiology, Clinical Manifestations, and Outcome of Mucormycosis in Solid Organ Transplant Recipients: A Systematic Review of Reported Cases.

Mucormycosis is an emerging disease primarily affecting the immunocompromised host, but scarce evidence is available for solid organ transplant recipients (SOTRs). We systematically reviewed 183 cases occurring in SOTRs, exploring epidemiology, clinical characteristics, causative pathogens, therapeutic approaches, and outcomes. Kidney transplants accounted for half of the cases, followed by heart (18.6%), liver (16.9%), and lung (10.4%). Diagnosis showed a dichotomous distribution, with 63.7% of cases reported within 100 days of transplantation and 20.6% occurring at least 1 year after transplant. The 90-day and 1-year mortality rates were 36.3% and 63.4%, respectively. Disseminated disease had the highest mortality at both time points (75% and 93%). Treatment with >3 immunosuppressive drugs showed a significant impact on 90-day mortality (odds ratio [OR], 2.33; 95% CI, 1.02-5.66; P = .0493), as did a disseminated disease manifestation (OR, 8.23; 95% CI, 2.20-36.71; P = .0027) and the presence of diabetes (OR, 2.35; 95% CI, 1.01-5.65; P = .0497). Notably, prophylaxis was administered to 12 cases with amphotericin B. Further investigations are needed to validate these findings and to evaluate the potential implementation of prophylactic regimens in SOTRs at high risk.

Coexisting Chronic Rhino-Cerebral Mucormycosis and Actinomyces Infection: A Case Report and Review of the Literature.

Fungal rhino-orbital-cerebral infections present significant treatment challenges, especially in immunocompromised individuals, such as those with diabetes. These infections seldom occur with bacterial co-infections, which complicate their management. This report presents the case of a 74-year-old diabetic male with a long-standing history of left malar pain who experienced rhinorrhea, nasal congestion, and confusion. Diagnostic imaging revealed angioinvasive fungal sinusitis, ultimately attributed to chronic mucormycosis (CM) with concurrent Actinomyces infection, a rarely reported occurrence. We employed a comprehensive treatment strategy, which resulted in a successful recovery after 24 days. Although CM is rare, accounting for approximately 5.6% of cases with mucormycosis, it requires thorough diagnostic evaluation and prolonged treatment. The rarity of co-infections like the one we describe underscores the need for an integrated management approach. Histopathological analysis serves as the gold standard for diagnosis, with treatment typically involving surgical and extensive antifungal interventions.

Magnetic Resonance Imaging in COVID-19 Associated Rhino-Sinusal Mucormycosis.

Rhino-sinusal mucormycosis is an acute invasive fungal infection rarely encountered in the clinical setting, occurring in severe immunosuppressed patients. However, in patients suffering from COVID-19 disease a dramatic increase in the incidence of mucormycosis has been recorded. The aim of the study is to discuss the MRI findings of patients with COVID-19 associated mucormycosis. This is a retrospective review of 10 hospitalized and operated patients in three Otolaryngologic Departments between the 1st of February 2021 and the 30th of October 2021. All patients presented nasal mucormycosis, histologically verified along with documented SARS-CoV-2 positive RT-PCR test. The sinus involvement, extra sinus spread and peri-sinus invasion were documented in all patients. The correlation between MRI and intra-operative findings was also assessed. The black turbinate sign and peri-antral soft tissue infiltration are early MRI signs characteristic of mucormycosis. Moreoever, MRI has a significantly high positive predictive value for intra-operative findings in COVID-19 associated mucormycosis.

Disseminated Cutaneous Mucormycosis Developing in Peristomal Pyoderma Gangrenosum.

A patient on long-term glucocorticoid therapy for peristomal pyoderma gangrenosum (PPG) who developed mucormycosis (MM) of the wound with dissemination was presented. The importance of skin biopsy, together with clinical evaluation in patients with PPG who are resistant to conventional therapy or who develop new symptoms related to their PPG is stressed. The risk and pathogenesis of invasive fungal infections with long-term corticosteroid therapy were explored. The epidemiology and detection of mucormycosis is discussed in this article.

An interesting report of COVID-19 associated mucormycosis (CAM) cases by two different species of Mucorales.

During surge of COVID-19-associated mucormycosis (CAM), we identified five cases of CAM where two different species of Mucorales were isolated. All had history of diabetes mellitus and presented with clinical features suggesting rhino-orbital mucormycosis. The patients grew different species from their nasal scraping/biopsy samples, Rhizopus arrhizus, R. homothallicus (n = 2); R. homothallicus, Lictheimia corymbifera (n = 1); R. arrhizus, Mucor spp (n = 1); and L. corymbifera, Apophysomyces variabilis (n = 1). All patients underwent surgical and medical (liposomal amphotericin B) treatment. All, except one growing A. variabilis and L. corymbifera survived. Mixed infection by more than one Mucorales in CAM is unique and warrants epidemiological investigation.

Utility of Itraconazole in Combination with Liposomal Amphotericin B in Rhizopus oryzae Associated Mucormycosis-An Exploratory Study.

BACKGROUND: During the COVID-19 pandemic-associated mucor epidemic, acute antifungal drug shortage necessitated the exploration of other antifungals based on culture sensitivity. Itraconazole is a cheap, safe, and effective antifungal in sensitive cases. METHODOLOGY: We enrolled itraconazole-sensitive COVID-19-associated mucormycosis during the mucormycosis pandemic. After the intensive phase course of liposomal amphotericin B, Itraconazole was offered in susceptible cases during the maintenance phase along with standard of care. These patients were clinically and radiologically followed for 6 months. RESULTS: We enrolled 14 patients (Male: Female-11:3) of Rhino-orbito-cerebral mucormycosis (ROCM) which included 12 diabetics. All patients had facial swelling, orbital swelling, visual impairment, and headache. MRI showed involvement of bilateral sinus (10/14), orbital extension (13/14), cavernous sinus (5/14), cerebral part of the internal carotid artery (3/14), and brain infarcts (4/14). All 14 patients showed sensitivity to Itraconazole with 12 having minimum inhibitory concentration (MIC) ≤ 1 µg/ml and 2 having MIC ≤ 2 µg/ml. Follow-up at 6 months showed clinical improvement in the majority (11/14) and radiological improvement in six out of seven scanned patients. CONCLUSION: Our study shows the potential therapeutic role of oral Itraconazole in ROCM.

Mucormycosis Superinfection of a Chemical Burn.

Mucormycosis is an uncommon infection but is increasing in prevalence. Cutaneous disease is associated with burns and traumatic injuries. Cutaneous mucormycosis is the least deadly form but mortality is still approximately 36%. Burn superinfection with mucormycosis is increasingly common and can be an insidious process which may not present until disease disseminates. We present the case of a 30-year-old male who presented to the Emergency Department for rash. A rash with yellow crusting was noted to involve his scalp, face, ear, R shoulder, and parts of both feet. He had been placed on antibiotics by an urgent care a few days prior to presenting. He denied systemic symptoms, chemical exposure, change in detergent, auto-immune diseases, or travel. Patient has a history of intravenous opioid and dissociative abuse and had multiple episodes of syncope- including at his work in a factory where there were hot metals, refrigerants, and numerous corrosive chemicals. Surgical debridement revealed mucormycosis on pathology. Patient was treated with isavuconazole, surgical debridement and skin grafting. He experienced complete recovery.

Agreement between two real-time commercial PCR kits and an in-house real-time PCR for diagnosis of mucormycosis.

Mucormycosis is a severe and emerging invasive fungal infection associated with high mortality rates. Early diagnosis is crucial for initiating specific antifungal treatment, with molecular tools currently representing the most efficient diagnostic approach. Presently, a standardized in-house real-time PCR method is widely employed for diagnosing mucormycosis. Our study aimed to evaluate the agreement for the Mucorales DNA detection between two commercial real-time PCR assays-the Fungiplex Mucorales Real-Time PCR Kit and the MycoGENIE Aspergillus-Mucorales spp. Real-Time PCR Kit-in comparison with the in-house PCR. We retrospectively analyzed 58 samples previously identified as positive for Mucorales using the in-house PCR. These samples, obtained from 22 patients with proven or probable mucormycosis, were tested with both commercial kits. Additionally, samples from 40 patients without mucormycosis served as negative controls. Our findings revealed that the MycoGENIE Kit demonstrated superior performance in detecting Mucorales DNA in samples identified as positive by the in-house PCR. Notably, we observed minimal variability in cycle threshold (CT) values when comparing the results of the MycoGENIE Kit with those of the in-house PCR, with an average difference of 1.8 cycles. In contrast, the Fungiplex Kit exhibited a larger discrepancy in CT values compared to the in-house PCR, with an average difference of 4.1 cycles. The MycoGENIE Kit exhibited very good agreement (kappa of 0.82) with the in-house PCR for detecting Mucorales DNA across various sample types. These findings are important for the choice of kits that could be used to diagnose mucormycosis in clinical microbiology laboratories. IMPORTANCE: Early diagnosis of mucormycosis is crucial for initiating effective treatment. The detection of Mucorales DNA by PCR in serum has revolutionized the diagnosis of this infection. However, the use of in-house methods can be time consuming. The availability of a commercial kit eliminates the need for in-house assay development, reducing laboratory workload and ensuring consistent performance across different healthcare settings. Currently, there are several commercial assays available, but many have limited evaluation. In this study, we compared two commercial kits and found that the MycoGENIE Kit offers a promising alternative to the in-house method.