Chronic cutaneous mucormycosis is a rare condition distinct from the acute form, characterized by a prolonged, indolent course and varied clinical presentations. This study presents a 5-year experience from a tertiary dermato-mycology clinic, identifying six cases, the majority of whom were immunocompetent, with trauma history reported in four patients. The median duration from symptom onset to diagnosis was 60 months. The primary pathogens identified were Rhizopus arrhizus, Mucor variabilis, and Lichtheimia ramosa. Histopathological analysis demonstrated the absence of fungal angioinvasion, a hallmark of acute mucormycosis, which likely accounts for the slower progression observed in chronic cases. Systemic Amphotericin B treatment achieved favourable outcomes in most patients though significant morbidity persisted in some cases. This case series underscores the clinical and pathological distinctions of chronic cutaneous mucormycosis, highlighting the potential influence of host factors and environmental conditions on chronicity. The predominance of Rhizopus arrhizus suggests that chronicity is driven more by hostpathogen interactions than fungal species-specific factors. Increased recognition of the atypical clinical features, such as diverse cutaneous manifestation and slower progression course, as well as the utilization of diagnostic tools including histopathology, fungal culture, and advanced molecular techniques, is essential for the timely diagnosis of this rare presentation.

We analyzed mucormycosis data from the Zygomyco.net registry (2009-2022), encompassing cases from 16 countries. India, Russia and the Czech Republic provided the largest contributions. India reported the highest case number, consistent with its substantially higher incidence compared to that of high-income countries. Among the 382 patients with mucormycosis, 236 (61.8%) were male (male-to-female ratio 1.6). The median age was 48 years [interquartile range (IQR) 32-60]. There were 59 pediatric patients (median age ranging from < 1 month to 19 years). Diabetes mellitus type 2 was the most common underlying condition (39%), with significant geographic variation (> 70% of cases in India and Iran but only 6.9% in Europe). Hematologic malignancies (HM, 31.4%), the second most common underlying condition, were absent in India and Iran. The primary clinical presentations were rhino-orbito-cerebral mucormycosis (ROCM, 36.6%), pulmonary (33.2%) and cutaneous mucormycosis (17.5%). Patients with diabetes mellitus typically developed ROCM (55.9%), while pulmonary infections were more common in those with HM or hematopoietic cell transplantation (HCT) (47.5%, p < 0.001). Rhizopus was the leading fungal genus (58%), followed by Lichtheimia (13.7%) and Mucor (7%), with regional variations. Pulmonary infections in HM patients were linked to L. corymbifera and R. microsporus, while Apophysomyces spp. and Saksenaea spp. were more frequent in Indian healthcare-associated cutaneous cases. Concomitant infections were observed in 8.7% of patients with HM, complicating diagnosis and treatment. In most of them (57.1%), Aspergillus spp. was involved. Improved diagnostic practices, including direct microscopy and cultures, showed higher positivity rates, although PCR remained underutilized. Antifungal therapy, primarily with an amphotericin B formulation, combined with surgery, was the most common therapeutic approach. Overall mortality was high (47.8%), particularly in disseminated or advanced ROCM cases. Multivariable analysis identified older age, advanced ROCM, and HM/HCT as independent mortality risk factors (p < 0.05); whereas localized sinusitis and combined medical and surgical therapy were independently associated with improved outcomes (p < 0.006). This study underscores regional disparities in the mucormycosis epidemiology and species distribution. Improved early detection is needed, particularly in immunocompromised populations with HM. Enhanced surveillance and tailored public health strategies are crucial to address this ongoing global health threat.

This study is a prospective observational study conducted over two years from December 2020 to March 2023 at the Department of Plastic and Reconstructive Surgery.

To evaluate the outcomes of delayed reconstruction in patients with maxillectomy defects post-COVID-19 associated mucormycosis, focusing on safety, morbidity, and aesthetic results.

Fifty patients with post-COVID-19 mucormycosis and maxillectomy defects without skin involvement were included. These patients underwent radical debridement and were treated with Amphotericin B followed by Posaconazole therapy until clinical and radiological resolution of the disease. Reconstruction was performed after a minimum of six months post-maxillectomy. Flaps used for reconstruction included the radial forearm free flap (RAFF), anterolateral thigh flap (ALT), and free fibula osteomyocutaneous flap, planned using a 3D-printed model. Follow-up was conducted weekly for the first month and monthly for the next two months, with semiannual visits thereafter.

Of the 50 patients, 42 % were male, and 58 % were female, with a mean age of 43 ± 8.75 years. Most patients (88 %) were diabetic. Maxillectomy defects were categorized as type IIA, IIB, IIIA, IIIB, and IV based on the Cordeiro classification. Four flaps (8 %) required re-exploration, with three salvaged. Complications included marginal flap necrosis (4 %) and oro-nasal fistula (2 %). The average hospital stay was six days, extended to ten days for re-explored cases. Flap dimensions varied with the largest being 62 cm² for the free fibula flap.

Delayed reconstruction using free flaps in patients with post-COVID-19 mucormycosis maxillectomy defects without skin involvement is a safe approach with minimal morbidity. This method allows confirmation of disease resolution before major reconstructive surgery, resulting in excellent aesthetic and functional outcomes.

Invasive fungal diseases are associated with significant morbidity and mortality, especially among immunocompromised patients, and often prompt for rapid and aggressive treatment aiming cure. Due to the expanding magnitude of patients burdened by chronic immunosuppression and affected by fungal diseases, the diversity of clinical settings has risen. This often results in prolonged therapy (induction, consolidation and maintenance) associated with potentially severe side effects, and clinicians face the challenging decisions of when and how to stop anti-fungal therapy. Adequate duration of therapy is poorly defined, hampered by the lack of dedicated trials to the question, the heterogeneity of cases (type of fungal pathogen, localization of infection, underlying host conditions) and various confounding factors that may influence the clinical response (e.g. persistence vs recovery of immunosuppression, impact of surgery). In this review, we aim to evaluate the existing data underlying the guidelines and recommendations of treatment duration for the most frequent invasive fungal diseases (cryptococcal meningitis, Pneumocystis pneumonia, invasive aspergillosis, invasive candidiasis and mucormycosis), as well as specific localizations of deep-seated diseases (osteo-articular or central nervous system diseases and endocarditis) and emerging considerations and strategies.

To document the treatment outcomes of orbital cellulitis in COVID-19-associated mucormycosis cases after timely transcutaneous retrobulbar amphotericin B (TRAMB) injections and sinus debridement by functional endoscopic sinus surgery (FESS), with or without medial orbital wall decompression and lateral canthotomy.

This retrospective observational study was conducted in the mucormycosis ward of a tertiary referral centre in Andhra Pradesh from May 2021 to September 2021. All patients with a history of COVID-19 infection and biopsy-proven, radiologically confirmed mucormycosis were included in the study and treated using a multidisciplinary approach with systemic and local antifungals and sinus debridement by FESS, with or without medial orbitotomy and lateral canthotomy.

Forty-six patients met the inclusion criteria. The identified risk factors were diabetes mellitus (80%), a history of steroid usage (59%) and raised serum ferritin levels (87%). The most common clinical presentation was diminution of vision with proptosis (65.2%), followed by ophthalmoplegia (54.34%). All patients received systemic antifungals and underwent FESS. TRAMB injections (three to six doses) were given to 44 patients. Of the 46 patients, 30 with mild to severe proptosis underwent medial orbital wall decompression, and 10 patients also lateral canthotomy. Clinical and radiological improvement was observed within 10 days postoperatively in 36 patients.

In patients with orbital cellulitis secondary to mucormycosis, early surgical intervention under antifungal coverage may allow complete resolution of orbital mucormycosis, preventing vision loss, morbidity and mortality.

Patients with hematopoietic malignancies (HM) are often immunocompromised and, therefore, susceptible to developing invasive fungal infections, including pulmonary mycosis. Surgical resection is indicated for localized pulmonary mycosis refractory to antifungal agents. This study investigated the feasibility and outcomes of minimally invasive surgery for pulmonary mycosis patients complicated with HM.

We retrospectively reviewed 56 cases of surgically treated pulmonary mycosis among the 3994 lung resections performed in our department between 2011 and 2020, focusing on the 19 cases under treatment for HM.

All patients underwent 3-port video-assisted thoracoscopic surgery, including one patient converted to open surgery. The 30 day mortality rate was zero. The overall survival rate 1 year after surgery was 63.2%. No relapse of mycosis was observed, and the majority of the cause of death was the progression of HM. The rate of major postoperative complications was comparable between the patients with HM (3/19) and without HM (5/37), despite the patients with HM having a higher frequency of immunocompromised status than those without HM. Most patients who underwent surgery before hematopoietic stem cell transplantation (HSCT) had leukocytopenia, while all patients who underwent surgery after HSCT received immunosuppressants. Mucormycosis was observed in 13 out of 19 patients (68%) with HM, and it was significantly associated with preoperative pancytopenia and usage of immunosuppressants.

Minimally invasive surgery was feasible for pulmonary mycosis complicated with HM despite the high frequency of immunosuppression. These findings will deepen our understanding of pulmonary mycosis associated with HM and may improve perioperative patient care.

Pulmonary mucormycosis is a rare and often fatal fungal infection. Identifying high-risk factors for pulmonary mucormycosis holds the potential to improve patient outcomes. This study aimed to identify the clinical characteristics and risk factors associated with pulmonary mucormycosis outcomes in a Chinese cohort.

A retrospective analysis was conducted on 37 patients diagnosed with pulmonary mucormycosis, focusing on clinical records, laboratory findings, and computed tomography (CT) imaging. Diagnosis was primarily based on histopathology or next-generation sequencing.

The median age of the patients was 55 years, and the most common underlying conditions were hematological malignancies, diabetes, and organ transplantation. Imaging frequently revealed bilateral lung involvement with ground-glass opacities and nodular lesions. The overall mortality rate was 29.7%, with significant risk factors for 90-day mortality including hypertension (Hazard Ratio [HR] = 3.36, 95% Confidence Interval [CI] = 1.01-11.12, P = 0.048), organ transplantation (HR = 4.93, 95% CI = 1.48-16.4, P = 0.009), and immunosuppression (HR = 8.83, 95% CI = 1.13-69.14, P = 0.038).

Early suspicion and timely diagnostic measures, such as biopsy or metagenomic sequencing, are crucial for improving patient outcomes. These findings underscore the importance of recognizing and managing pulmonary mucormycosis in high-risk populations.

Mucormycosis is a highly invasive and rare opportunistic infection caused by mucor fungi, characterized by challenging diagnosis and rapid disease progression. It predominantly affects patients with compromised immune systems due to various reasons, such as kidney failure, long-term use of antibiotics or corticosteroids. We recently successfully treated a pediatric patient with rapidly progressive glomerulonephritis accompanied by severe cutaneous mucormycosis. To our knowledge, this is the first reported case of rapidly progressive glomerulonephritis nephritis accompanied by dermatophytosis in a pediatric patient. In this case, we share our management experience, including special nursing experience. Cutaneous mucormycosis progresses quickly and is difficult to diagnose and treat, especially in children with compromised immune function, warranting high vigilance from clinicians and nursing staff. Early diagnosis and targeted treatment are crucial for improving the prognosis of patients. Therefore, once there is a suspicion of a mucormycosis infection, we recommend the early application of various testing methods such as fungal culture, skin biopsy and genetic testing in order to to promptly confirm the diagnosis.

Mucormycosis is a rare, life-threatening opportunistic infection primarily affecting immunocompromised patients. The available literature on Rhizomucor pusillus (R pusillus) infections of the central nervous system (CNS) in children is very limited. We present the case of an immunocompromised adolescent with intracranial mucormycosis due to R pusillus manifesting with stroke-like symptoms. This case highlights this rare condition's diagnostic complexity and management challenges. We include a review of the available literature on pediatric R pusillus CNS infections to increase awareness among health care providers.

This study represents 2 cases of kidney transplant recipients (KTRs) with invasive pulmonary Rhizopus infection, successfully treated with oral isavuconazole monotherapy without lobectomy. The rapid detection via mNGS of bronchoalveolar lavage fluid enabled early diagnosis and timely intervention, resulting in complete recovery and stable graft function. The literature review revealed a 16.7% mortality rate among 13 cases, with a higher mortality rate of 66.7% among patients receiving antifungal treatment without surgical intervention. Our findings underscore the efficacy of isavuconazole as a first-line monotherapy, characterized by lower nephrotoxicity and fewer interactions with immunosuppressants, and emphasize the crucial role of metagenome next-generation sequencing (mNGS) in early diagnosis of invasive mucormycosis in high-risk population.

Mucormycosis is a life-threatening infection associated with high morbidity and mortality. Rapid and accurate diagnosis is essential for improving patient outcomes. Conventional diagnostic methods, such as histopathology and culture, are limited by low sensitivity and prolonged turnaround times, while commercial polymerase chain reaction (PCR) assays are costly and may lack specific genus or species targets. Here, we present a novel molecular diagnostic workflow to facilitate the rapid detection of Mucorales directly from clinical specimens. This workflow integrates two in-house in vitro diagnostic PCR assays: a real-time, qualitative Pan-Mucorales PCR, followed by a real-time multiplex genus/species-specific PCR targeting Rhizopus arrhizus, Rhizopus microsporus, and Mucor spp. Specificity of the assays was validated using cultured isolates of Mucorales, as well as non-Mucorales fungi and bacteria. The diagnostic performance was assessed across 166 clinical specimens (70 Mucorales-positive and 96 negative), confirmed by an in-house panfungal PCR and DNA sequencing protocol. Specimens studied included fresh and formalin-fixed paraffin-embedded tissues, fluid, bronchoalveolar lavage/washing fluid, fine needle aspirate, cerebrospinal fluid, and bone. The Pan-Mucorales PCR demonstrated 98.6% sensitivity and 100% specificity, while the multiplex genus/species-specific PCR assay yielded sensitivities of 93.8% for R. arrhizus, 70.8% for R. microsporus, and 75% for Mucor spp., each with 100% specificity. Concordance with the panfungal PCR (>99% for Pan-Mucorales PCR and >89% for multiplex PCR) was high, supporting the robustness of the workflow. This diagnostic approach has the potential to significantly reduce turnaround times, labor and costs, while streamlining the diagnostic process through timely, precise diagnostics.

Mucorales fungi, identified collectively as a high-priority pathogen on the World Health Organization fungal priority pathogens list, are the causative agents of mucormycosis. Mortality is high (up to 80%), and early, accurate diagnosis is critical to enable timely initiation of targeted antifungal therapy and surgical debridement for source control to optimize patient outcomes. In our laboratory, as in many others, the current standard for the diagnosis of mucormycosis is histopathology and culture-based methods supplemented by panfungal PCR assay/DNA sequencing; however, this process may take 7 days, with considerable labor and cost implications. Here, we present two Mucorales-specific real-time PCR assays, which when used sequentially, reduce diagnostic turnaround time and costs to detect three common agents of mucormycosis-Rhizopus microsporus, Rhizopus arrhizus, and Mucor species. This approach not only improves diagnostic efficiency and integration into workflow but can facilitate surveillance through accurate genus- and species-level identification.

The discovery of N6-methyladenine (6mA) in eukaryotic genomes, typically found in prokaryotic DNA, has revolutionized epigenetics. Here, we show that symmetric 6mA is essential in the early diverging fungus Rhizopus microsporus, as the absence of the MT-A70 complex (MTA1c) responsible for this modification results in a lethal phenotype. 6mA is present in 70% of the genes, correlating with the presence of H3K4me3 and H2A.Z in open euchromatic regions. This modification is found predominantly in nucleosome linker regions, influencing the nucleosome positioning around the transcription start sites of highly expressed genes. Controlled downregulation of MTA1c reduces symmetric 6mA sites affecting nucleosome positioning and histone modifications, leading to altered gene expression, which is likely the cause of the severe phenotypic changes observed. Our study highlights the indispensable role of the DNA 6mA in a multicellular organism and delineates the mechanisms through which this epigenetic mark regulates gene expression in a eukaryotic genome.

Intra-abdominal and gastrointestinal mucormycosis are less frequent than rhino-orbito-cerebral and pulmonary mucormycosis, but highly lethal. Their diagnosis remains challenging due to the non-specific clinical presentation. We collected English-language cases of intra-abdominal and gastrointestinal mucormycosis in non-haematological and non-neonatal patients published up to October 2024. This review analysed the epidemiological, clinical, and therapeutic charts of 290 cases. A proportion of 53.4% were reported from India and the USA. The main predisposing conditions were diabetes, solid organ transplant, ICU, and corticosteroid treatment. The most common site was the stomach (53.8%). Gastrointestinal perforation, skin breakdown, and abdominal wall infection were sources of intra-abdominal localisation. The most common symptoms were abdominal pain, vomiting, and gastrointestinal bleeding. The diagnosis relied on histology (93.8%), mycology with microscopy and culture (38.8%), and molecular methods (9.9%). Mortality (52.9%) was lower when treatment was intravenous amphotericin B, combined or not with surgery. Prompt treatment, essential for a favourable outcome, relies on early suspicion and diagnosis. Gastrointestinal and intra-abdominal mucormycosis should also be suspected in patients admitted in ICU with ventilation/nasogastric tube and corticosteroids and those with abdominal trauma or surgery, presenting abdominal distension, pain, and GI bleeding. Mycological diagnosis including direct examination, culture and Mucorales qPCR on tissue should assist with rapid diagnosis and thus treatment.

Mucormycosis is a life-threatening complication that occurs in haematopoietic stem cell transplantation (HSCT) recipients. Among mucormycosis patients, those infected with Cunninghamella bertholletiae have the poorest prognosis because of the high virulence and angioinvasive nature of this organism. Despite its high vascular invasiveness, pseudoaneurysm caused by C. bertholletiae in HSCT recipients has rarely been reported.

An 8-year-old HSCT recipient experienced recurrent fever, cough and pain after HSCT. Teicoplanin, acyclovir, posaconazole and caspofungin were used for infection prophylaxis. The sputum, stool, urine, peripheral blood and central venous catheter (CVC) blood culture results were negative. Next-generation sequencing (NGS) of the peripheral blood, pleural effusion and bronchoalveolar lavage fluid revealed the presence of C. bertholletiae, and amphotericin B combined with posaconazole was administered; however, the infection progressed. Fibreoptic bronchoscopies revealed that C. bertholletiae had invaded the bronchial wall, and enhanced computerized tomography (CT) revealed a pseudoaneurysm of the descending aorta resulting from C. bertholletiae. Debridement and vessel replacement were considered but not performed because of the severity of the infection and the patient's poor physical condition. Unfortunately, the patient died from pseudoaneurysm rupture with no presymptoms 56 d after HSCT.

For the first time, we report pseudoaneurysm secondary to C. bertholletiae infection in a HSCT recipient, highlighting the importance of clinical awareness of vessel lesions resulting from C. bertholletiae and emphasizing the value of enhanced CT for the early detection of vessel lesions in this rare infection.

Mucormycosis is a severe mold infection primarily affecting immunocompromised patients. Neutropenia, steroid use, hyperglycemia, and diabetes are recognized as significant risk factors. Cunninghamella species are rare pathogenic fungi associated with high mortality rates and multidrug resistance. However, there have been no reports of C. phaeospora being identified as the causative agent of clinical infection. We report a case of a 71-year-old man who developed right middle lobe pneumonia during salvage induction therapy for relapsed acute myeloid leukemia. Based on the clinical course, mucormycosis was suspected, and antifungal therapy was initiated with isavuconazole (200 mg every 8 hours for six doses, followed by 200 mg daily) and later switched to liposomal amphotericin B (5 mg/kg/day). Despite these interventions, the patient's respiratory failure progressed, culminating in a fatal hemorrhagic infarction of the right lung. An autopsy revealed invasive fungal involvement in multiple organs, including the lungs and liver. Genetic identification of the isolated fungi demonstrated C. phaeospora, confirming disseminated C. phaeospora infection. Susceptibility testing showed high Minimum Inhibition Concentrations/Minimum Effective Concentrations to all tested antifungal agents. This is the first reported case of disseminated infection caused by C. phaeospora with multidrug resistance. This case highlights the diagnostic and therapeutic challenges associated with rare pathogenic fungi. It underscores the importance of early identification of Mucorales, including susceptibility testing, to optimize antifungal therapy and consider appropriate surgical interventions. Further research is required to elucidate the mechanisms of antifungal resistance and clinical characteristics of C. phaeospora.

Illicit drug use in the United States continues to rise, alongside an increasing number of severe infections associated with drug use. Surveillance studies report that 28%-34% of candidemia cases are linked to intravenous drug use, with Candida albicans being the most commonly isolated species, followed by Candida parapsilosis and Candida glabrata. Marijuana use is associated with lung infections caused by Aspergillus and the Mucorales, showing a 3.5-fold increased risk of mold infections and a 2.2-fold increased risk for other fungal infections. Intravenous drug use also presents a recognized risk factor for Aspergillus and Mucorales infections. Additionally, substances like cannabis, methamphetamines, and opioids share metabolic pathways with triazoles, a class of antifungal, and terbinafine through the CYP enzyme system. These antifungal drugs strongly inhibit CYP3A4 and CYP2D6, leading to potential drug interactions, adverse effects, overdose risks, and even death.

This case report describes a rare occurrence of palatal mucormycosis in a 45-year-old immunocompetent female patient who developed black discoloration of the palate following a tooth extraction. Initial diagnostic investigations and superficial biopsy revealed aspergillosis; however, further postoperative histopathological examination confirmed mucormycosis. Aggressive surgical intervention, including maxillectomy, alveolectomy, and functional endoscopic sinus surgery, combined with targeted antifungal therapy, facilitated successful treatment. The importance of timely diagnosis and comprehensive management in mucormycosis cases, even among immunocompetent patients, is highlighted.

The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy partnered with its Transplant Infectious Disease Special Interest Group to create a guideline focusing on non-Aspergillus invasive molds, which are uncommon yet lethal invasive fungal diseases in the peri-hematopoietic cell transplant (HCT) period. We used a compendium-style approach by dissecting this broad, heterogeneous, and highly complex topic into a series of standalone frequently asked questions (FAQs) and tables. Adult and pediatric infectious diseases and HCT content experts developed, then answered FAQs, and finalized topics with harmonized recommendations. All the evidence for non-Aspergillus invasive mold infection is non-RCT and mostly level III, therefore there are no recommendation grades, and instead key references are provided. Through this format, this "8th" topic in the series focuses on the relevant risk factors, diagnostic considerations, prophylaxis, and treatment approaches relevant to rare mold infections in the pre- and post-transplant periods.

Mucormycosis is a rare subcutaneous fungal disease caused by mucormycoides, which can affect the skin, nose, brain, lung, gastrointestinal tract and other system. Cutaneous mucormycosis accounts for 10-19% of mucormycosis and is one of the most common types only second to the lung and naso-brain mucormycosis. Here we report a case of periorbital primary cutaneous mucormycosis in a latent immunocompromised male with a suspected history of herpes zoster on the right head and face. He was successfully treated with local injection and oral antifungal drugs combined with debridement, and without recurrence after more than one-year follow-up.

Isavuconazole, a triazole-class antifungal, is effective and safe for both primary treatment and salvage therapy in a variety of fungal infections. This article reviews recent knowledge on the role of this antifungal in the treatment of mucormycosis and breakthrough invasive fungal infections (bIFI) during antifungal therapy. Isavuconazole has demonstrated favorable clinical outcomes and a good safety profile in various patient populations with mucormycosis, including those with comorbidities such as diabetes mellitus or severe immunosuppression. Particularly noteworthy is the fact that drug interactions in patients with mucormycosis, where a solid organ transplant was a predisposing factor, have been effectively managed. In the treatment of bIFIs, the use of isavuconazole requires a thoughtful reflection about the fungal species involved and their susceptibility profiles. This is highly dependent on the antifungal agent administered before the onset of bIFI. Early diagnosis and appropriate antifungal therapy are essential to improve outcomes in patients with mucormycosis and bIFIs. Isavuconazole represents a valuable option for managing these complex infections.

Rhino-orbital-cerebral mucormycosis (ROCM) is the most common (45%-74%) mucormycosis in India. With contemporary medical care, ROCM has a mortality rate of 40%-50% and 70% of survivors are left with residual defects. Recently, several cases of mucormycosis in people with COVID-19 have been increasingly reported worldwide, from India, due to immune dysregulation caused by SARS-CoV-2. To reduce the high mortality rate and residual defect in most survivors under the guidelines of the Ministry of AYUSH, the Government of India recommended homoeopathy as an add-on therapy to maximize the effectiveness of standard treatment in conventional therapy.

This study aimed to evaluate the role of existing homoeopathic treatment as an adjuvant therapy in patients with COVID-19-related ROCM and enhancing the survival of the patients hospitalized due to COVID-19 infection and to access the initial treatment response and duration required for significant or complete recovery in patients receiving adjuvant treatment.

This superiority, randomized controlled clinical trial would include two parallel comparator groups A and B. Group A would be the experimental group and would receive homoeopathic treatment along with the standard line of treatment as per investigational medicinal product (IMP) and group B would be the control arm and would receive standard line of treatment as per IMP along with identical placebo. Allocation would be 1:1 through randomization. Based on the inclusion and exclusion criteria, 36 participants per arm would be screened. Participants would be assessed clinically twice a day and magnetic resonance imagery or endoscopy cum-biopsy would be assessed on days 1, 14, and 28. Laboratory investigations may vary as per demand of disease conditions.

In India, the COVID-19 pandemic, particularly during the second wave, resulted in a surge of mucormycosis cases among patients with COVID-19. At the time this protocol was being developed, there was a significant spike in mucormycosis cases in India, particularly in Mumbai (June 2021). However, by the time the Central Council for Research in Homoeopathy obtained the necessary approvals and ethical clearance for the study, the incidence of mucormycosis had drastically declined (September 2021). As a result, the study was not initiated and registered. The authors feel it is their ethical responsibility to share the reviewed protocol with the medical community as a reference for future work.

This study aims to evaluate the role of existing homoeopathic medicines as an adjuvant therapy in managing COVID-19-related ROCM, potentially contributing to the use of homoeopathy as an evidence-based medical approach. The protocol can also serve as a valuable resource for clinicians and researchers addressing mucormycosis cases unrelated to COVID-19, particularly in immunocompromised patients. It would help ensure preparedness, whether or not sufficient evidence is available, in the event of a future health emergency.

PRR1-10.2196/57905.

Mucor lusitanicus has emerged as a model organism for studying RNAi in early-diverging fungi. This fungus exhibits intricate RNAi pathways that play crucial roles in regulating gene expression, destroying invasive exogenous genetic material, and controlling the movement of transposable elements (TEs) to ensure genome stability. One of the most fascinating RNAi pathways of this fungus is the non-canonical RNAi pathway (NCRIP), which is independent of Dicer and Argonaute proteins and uses the atypical RNase III R3B2 to degrade specific target messenger RNAs (mRNAs), playing an essential role in genome stability and virulence. Despite accumulating data suggesting that this pathway is a degradation mechanism, there has been no conclusive evidence. Here, we conducted a comparative transcriptomic analysis of mRNA and small RNAs regulated by r3b2, identifying 35 direct NCRIP targets. Most of these direct NCRIP targets correspond to TEs, highlighting the significant role of this RNAi pathway in TE control. Detailed functional analysis of the NCRIP targets confirmed the crucial role of r3b2 in regulating gene expression of protein-coding genes and controlling TEs other than centromeric GremLINE1 transposons, emphasizing the important role of r3b2 in genome stability. Interestingly, the RNAs of the NCRIP targets harbor a unique motif consisting of CAG repeats which are known to form hairpin structures which are targeted by RNA interference. Additionally, the generation of transformants expressing mRNAs containing the luciferase reporter gene along direct NCRIP targets reveals that this RNAi pathway is a true degradation mechanism for specific mRNAs. These results are expected to contribute to the understanding of the regulation of the NCRIP pathway through the analysis of its direct targets identified here.

Invasive fungal infection (IFI) due to moulds other than Aspergillus are a significant cause of morbidity and mortality. Non-Aspergillus mould (NAM) infections appear to be on the increase due to an ever-expanding population of immunocompromised hosts. In this review, Mucorales, Scedosporium species, Lomentospora prolificans and Fusarium species are examined in detail, and the microbiology, risk factors, diagnosis and treatment of emerging NAMs such as Paecilomyces variotti, Purpureocillium lilacinum and Rasamsonia are summarized. The challenges in diagnosis are emphasized and the emerging importance of molecular methods is discussed. Treatment of IFI due to NAMs is a multi-pronged and multi-disciplinary approach. Surgery, correction of underlying risk factors, and augmentation of the host immune response are as important as antifungal therapy. Many of these NAMs are intrinsically resistant to the currently licensed antifungal agents, so selection of therapy needs to be guided by susceptibility testing. There are new antifungal agents in development, and these have the potential to improve the efficacy and safety of antifungal treatment in the future. Ongoing research is required to fully delineate the epidemiology of NAM infections, and to develop better diagnostic tools and treatments so that outcomes from these infections can continue to improve.

Correct, rapid, and reliable filamentous fungi identification is crucial for timely diagnosis and therapy. We compared the performance of the FFLv4.0 MALDI Biotyper and MSI-2 to identify filamentous fungi from clinical isolates. We analyzed 307 clinical isolates of Aspergillus spp., Fusarium spp., and Mucorales and compared them to sequencing as the reference standard. The overall identification rates to genus (Mucorales), section (Aspergillus), and species complex (Fusarium) level were 96% (296/307) for FFLv4.0 and 78.5% (241/307) for MSI-2. By each genus, correct species identification was achieved by FFLv4.0 and MSI-2 as follows: 72.4% (165/228) and 55.3% (126/228) for Aspergillus species, 17.6% (6/34) and 38.2% (13/34) for Fusarium species, and 88.9% (40/45) and 55.5% (25/45) for the Mucorales. The rates of non-identification by FFLv4.0 and MSI-2, respectively, were 4% (9/228) and 18% (41/228) for Aspergillus spp., 0% and 17.6% (6/34) for Fusarium spp. and 4.4% (2/45) and 42.2% (19/45%) for the Mucorales. Misidentification rates by FFLv4.0 and MSI-2, respectively, were 16.2% (37/228) and 6.1% (14/228) for Aspergillus species, 67.6% (23/34) and 14.7% (5/34) for Fusarium spp., and 0% and 2.2% (1/45) for the Mucorales. The FFLv4.0 MALDI Biotyper outperformed MSI-2 in identifying filamentous fungi from liquid culture spectra.

Various species of fungi can be detected in the environment and within the human body, many of which may become pathogenic under specific conditions, leading to various forms of fungal infections. Antimicrobial peptides (AMPs) are evolutionarily ancient components of the immune response that are quickly induced in response to infections with many pathogens in almost all tissues. There is a wide range of AMP classes in humans, many of which exhibit broad-spectrum antimicrobial function. This review provides a comprehensive overview of the mechanisms of action of AMPs, their distribution in the human body, and their antifungal activity against a range of both common and rare clinical fungal pathogens. It also discusses the current research status of promising novel antifungal strategies, highlighting the challenges that must be overcome in the development of these therapies. The hope is that antimicrobial peptides, as a class of antimicrobial agents, will soon progress through large-scale clinical trials and be implemented in clinical practice, offering new treatment options for patients suffering from infections.

Rhinocerebral mucormycosis, an invasive fungal infection caused by Mucorales species, typically involves the paranasal sinuses, orbits, and central nervous system. Known for its aggressive nature, the infection often leads to severe complications and a high risk of mortality. Common risk factors include uncontrolled diabetes mellitus, immunosuppression, prolonged use of glucocorticoids, and hematologic malignancies. Patients with hematologic malignancies are particularly susceptible to this infection due to compromised immune function. This case report details an instance of acute lymphoblastic leukemia complicated by naso-ocular encephalomycosis, providing a comprehensive overview of its clinical presentation, diagnostic approach, therapeutic management, and prognosis. Additionally, preventive measures and early diagnosis are important in patients with hematologic malignancies.

Mucormycosis is a severe, opportunistic infection caused by Mucorales, a taxonomical group of thermotolerant fungi primarily affecting the immunocompromised. Intra-abdominal involvement in mucormycosis is a rare entity, particularly in immunocompetent individuals. We present a fatal case of gallbladder and renal mucormycosis in an immunocompetent female, leading to septic shock and death. The diagnosis was confirmed via histopathology following cholecystectomy for suspected gangrenous cholecystitis and open right nephrectomy due to kidney infarction. Quantitative polymerase chain reaction of the tissue identified the presence of Apophysomyces ossiformis. The clinical picture was confounded by ongoing sepsis due to a Klebsiella pneumoniae-infected retroperitoneal hematoma, non-specific imaging findings, and the absence of traditional risk factors for mucormycosis, leading to a delayed diagnosis. Despite surgical debridement, initiation of liposomal amphotericin B with posaconazole, and aggressive treatment in the intensive care unit, the patient succumbed to complications of mucormycosis. Despite adequate antibiotic coverage, this case underscores the importance of considering Mucorales infection in otherwise immunocompetent patients with a deteriorating clinical condition. Early diagnosis and appropriate intervention are essential in enhancing mucormycosis survivability, though mortality rates remain high in severe cases.

Mucormycosis is an aggressive and frequently lethal disease. Most patients with mucormycosis have poorly controlled diabetes mellitus and rhino-orbito-cerebral disease. Patients with hematologic malignancy and transplant recipients mostly present with rhino-orbito-cerebral or pulmonary disease. Prompt recognition of clinical symptoms and radiographic features of mucormycosis is required to establish timely diagnosis and initiate targeted therapy. Diagnosis is, historically, made by direct microscopy, culture, and pathology of biopsy tissue, but molecular methods are increasingly playing a role in establishing an earlier diagnosis. Treatment is multidisciplinary, involving early surgical intervention, antifungal therapy, and correction of underlying immune compromising risk factors when possible.

Invasive mould infections (IMI) cause substantial morbidity and mortality in populations at risk. Novel treatment approaches are urgently needed. Targeting immune checkpoints may reverse hyporesponsiveness of the innate and adaptive immune systems.

In this prospective, observational study, we investigated immune checkpoint expression levels on immune cells in patients with invasive aspergillosis (IA; n = 25) and mucormycosis (MU; n = 7). Healthy controls (HC; n = 5) and patients with matched haematological diseases but without IMI served as control populations (CP; n = 10). Multicolour flow cytometry analysis was used to compare immune cell subsets and the expression of immune-regulatory molecules in peripheral blood mononuclear cells (PBMCs).

Lymphocyte subsets and immune phenotypes in PBMCs were similar between patients with IMI and haematological CP, except for regulatory T cells, which were increased in PBMCs of patients with IA and MU compared to HCs. In IA and MU, PBMCs showed increased expression of immune checkpoint molecules compared to healthy controls and matched haematological CP, with this effect being more pronounced in IA than in MU. We found heterogeneous, disease-, molecule-, and patient-specific expression patterns of immune checkpoint molecules. For example, PD-1 expression was highest in MU PBMCs, followed by IA PBMCs, while HC PBMCs showed lower expression levels. Overall mortality in our patient population was 44.0% (IPA) and 80.0% (MU).

We report an immune phenotype consistent with T-cell exhaustion in IMI, indicating potential contributions from haematological treatment, underlying disease, and infection. However, the primary underlying cause remains unclear and requires further investigation. A marker that was notably higher in IMI patients was PD-1, and treatment approaches specifically targeting this molecule may be promising.

The objective of this study was to study the various outcomes among coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) in terms of morbidity and mortality.

A prospective study was done on 107 patients (60 male, 47 female) in the Department of Otolaryngology and Head and Neck Surgery, Government Medical College, Patiala, India, diagnosed with CAM from April 2021 to August 2021. The patients were managed both medically and surgically. The follow-up was done up to 2 years to assess the various outcomes.

Out of 107 patients, short-term (3 months) survival was 68.22%, and long-term (2 years) survival was 52.34%. Overall mortality was 47.66%, with short-term mortality of 31.77% and long-term mortality of 15.89%. Eye loss was seen in 17 patients, residual ophthalmoplegia in 12, palatal loss in 15, depression in 56, cerebrospinal fluid rhinorrhea in two, and recurrence in two patients.

In conclusion, despite early management and successful initial outcome, the patients are still haunted by the after-effects of CAM like residual morbidity in terms of eye and palate loss, ophthalmoplegia, and depression. Delayed mortality has also been noticed over 2 years of follow-up.

Mucormycosis is an invasive infection caused by fungi of the order Mucorales, typically affecting immunocompromised individuals, and rarely involving the gastrointestinal tract. We report two cases of gastrointestinal mucormycosis by Mucor indicus: a 77-year-old woman with a gastric ulcer and a 25-year-old man with liver lesions. Both were treated with surgery and liposomal amphotericin B; only one survived. Recognizing gastrointestinal mucormycosis in the correct clinical context is essential and requires timely surgical and antifungal treatment. 2012 Elsevier Ltd. All rights reserved.

Mucormycosis is a life-threatening fungal infection with high mortality in critically ill patients. Clinical manifestations and outcomes of mucormycosis in intensive care units (ICUs) remain poorly investigated.

We conducted a multicenter retrospective study including 43 adult patients with confirmed mucormycosis admitted to 14 tertiary ICUs between January 2014 and May 2022. Clinical characteristics, diagnostic approaches, treatment strategies, and outcomes were analysed.

The mean age was 56.8 ± 16.2 years, with 16/43 (37.2%) female patients. The 28-day survival rate was 46.5% (20/43). Lung involvement was predominant (29/43, 67.4%), and 29/43 (67.4%) patients received amphotericin B therapy. Survivors showed significantly better treatment response compared to non-survivors (16/20, 80% vs. 4/23, 17.4%, p < 0.001). Non-survivors demonstrated significantly higher levels of aspartate aminotransferase, C-reactive protein, and white blood cells, along with lower albumin levels. Metagenomic next-generation sequencing (mNGS) was associated with a shorter time to diagnosis. Multivariate analysis identified age, respiratory failure, time from symptom onset to diagnosis, and antifungal treatment response as independent predictors of 28-day mortality (AUC = 0.852).

In critically ill patients with mucormycosis, early diagnosis and prompt targeted therapy are crucial determinants of survival, with our newly developed prediction model providing a practical tool for risk stratification, while mNGS shows promise in expediting diagnosis.

Invasive pulmonary infections are a significant cause of morbidity and mortality in patients with hematological malignancies and hematopoietic stem cell transplantation (HCT) recipients. A delay in identifying a causative agent may result in late initiation of appropriate treatment and adverse clinical outcomes. We examine the diagnostic utility of PCR-based assays in evaluating invasive pulmonary infections from bronchoalveolar lavage (BAL). Patients with hematological malignancies and HCT recipients who underwent bronchoscopy with BAL from January 2020 to January 2024 for unexplained pulmonary infiltrates and had ≥1 PCR targeting Aspergillus, Mucorales, or Nocardia (Eurofins-Viracor, KS) were reviewed. Testing for microbiology and pathology except BAL PCRs to identify the etiology of pulmonary infiltrate was defined as standard-of-care. Invasive fungal diseases were defined as per European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) 2020 guidelines. Pulmonary nocardiosis was defined by a combination of clinical, radiographic, and microbiologic criteria. Of 134 patients, 77 were HCT recipients, and 70% were on antifungal agents. Thirty-two were diagnosed with infection with one of the three target pathogens, including 20 with probable or proven invasive pulmonary aspergillosis (IPA), seven with mucormycosis, and three with nocardiosis. For IPA, 19 were diagnosed by standard-of-care, and one (5%) was solely diagnosed by Aspergillus PCR. Mucorales PCR was positive in three of seven cases of proven mucormycosis, but the cultures were negative in all. All three nocardiosis cases were detected by PCR and culture. In our cohort, PCR targeting Mucorales and Nocardia can improve the early detection of invasive pulmonary infection, whereas Aspergillus PCR has a low added value when done in conjunction with standard-of-care, including BAL galactomannan.IMPORTANCEInvasive pulmonary infections are a significant cause of morbidity and mortality in immunocompromised patients. Timely diagnosis of invasive pulmonary infection reduces the time to targeted treatment initiation and improves clinical outcomes. The recent European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) update included the addition of serum or bronchoalveolar lavage (BAL) PCR as a method to determine probable Aspergillus disease. This reflects an increased utilization of PCR-based assays in the diagnosis of fungal diseases. Although PCR assays for Aspergillus diagnosis have been well characterized in the literature, their additive clinical utility in conjunction with BAL galactomannan index measurements remains unclear. Moreover, only a few reports characterize the analytic and clinical performance of Mucorales and Nocardia PCR.

Zygomycosis, also termed mucormycosis, is a rare yet highly fatal fungal infection caused by Mucorales species, notably Rhizopus spp.

This case study details a 72-year-old man with diabetes, pulmonary tuberculosis, and nephrotic syndrome who developed acute necrotizing fasciitis attributable to R. oryzae. Despite initial empirical antibiotic therapy, the infection progressed rapidly. Metagenomic next-generation sequencing (mNGS) facilitated a swift diagnosis, identifying R. oryzae in blood and drainage samples. The treatment included amphotericin B and isavuconazole, along with aggressive surgical debridement. The patient exhibited substantial improvement, and he was discharged after stabilization.

This case highlights the critical role of early diagnosis through mNGS and the need for a multidisciplinary approach to manage severe mucormycosis in immunocompromised patients.

Mucormycosis is an aggressive invasive fungal infection caused by molds in the order Mucorales. Early diagnosis is key to improving patient prognosis, yet it relies on insensitive culture or nonspecific histopathology. A pan-Mucorales-specific monoclonal antibody (mAb), TG11, was recently developed. Here, we investigate the spatiotemporal localization of the antigen and specificity of the mAb for immunohistochemistry.

We used immunofluorescence microscopy to assess antigen localization in 11 Mucorales species of clinical importance and live imaging of Rhizopus arrhizus germination. Immunogold transmission electron microscopy revealed the subcellular location of mAb TG11 binding. Finally, we performed immunohistochemistry of R arrhizus in an ex vivo murine lung infection model alongside lung infection by Aspergillus fumigatus.

Immunofluorescence revealed TG11 antigen production at the emerging hyphal tip and along the length of growing hyphae in all Mucorales except Saksenaea. Time-lapse imaging revealed early antigen exposure during spore germination and along the growing hypha. Immunogold transmission electron microscopy confirmed mAb TG11 binding to the hyphal cell wall only. The TG11 mAb stained Mucorales but not Aspergillus hyphae in infected murine lung tissue.

TG11 detects early hyphal growth and has valuable potential for diagnosing mucormycosis by enhancing discriminatory detection of Mucorales in tissue.

Mucormycosis is an infrequent fungal infection commonly seen in immunocompromised individuals. However, it can also occur in immunocompetent patients, especially following trauma. We present a case of a 15-month-old girl with increasing swelling and redness in her left eye after a minor traumatic injury. Imaging showed sinusitis with orbital involvement. Histopathology validated the diagnosis of mucormycosis caused by Rhizopus species. The patient had emergency surgery, followed by antifungal and antibiotic therapy. Despite febrile reactions to the treatment, the infection was managed, and the patient was discharged after 2 months. This case highlights the importance of considering mucormycosis in immunocompetent patients with unexplained ocular symptoms after trauma. Early diagnosis and aggressive treatment are essential for improving outcomes, especially in pediatric patients.