RARE DISEASE
Zygomycosis
Zygomycosis
Zygomycosis
Synonyms: Mucormycosis
Synonyms: Mucormycosis
Synonyms: Mucormycosis
Drug discovery
6
drugs
With orphan designations
Overview
Zygomycosis (Mucormycosis) is a life-threatening angioinvasive fungal infection caused by Mucorales molds, primarily affecting immunocompromised individuals such as those with diabetes mellitus, hematologic malignancies, or transplant recipients. Common presentations include rhino-orbital-cerebral, pulmonary, and cutaneous forms, characterized by rapid tissue necrosis. Diagnosis relies on histopathology and imaging, with aggressive treatment combining antifungals (liposomal amphotericin B) and surgical debridement [1][5][15][17].
Population
High-risk groups: Uncontrolled diabetes (especially ketoacidosis), hematologic malignancies, solid organ/stem cell transplants, long-term corticosteroid use, and COVID-19 patients with secondary immunosuppression [1][7][12][17].
Higher prevalence in India (~0.14/1,000 population) compared to Western countries (0.7–1.2/million) [7][17].
Burden
Mortality: 44%–96% depending on site (disseminated >90%, rhinocerebral ~60%) [9][14][17].
U.S. estimates: 1,140 hospitalizations (2019), 232 deaths (2021); global COVID-19-associated surges (e.g., 45,000+ cases in India, 2021) [4][7][14][17].
Healthcare costs: Direct medical expenses exceed $129M annually in the U.S., with prolonged hospital stays [4][14].
Therapies
First-line: Liposomal amphotericin B (5–10 mg/kg/day) ± early surgical debridement [3][8][13].
Salvage/adjunctive: Posaconazole/isavuconazole, iron chelation (deferasirox), and immunomodulators (e.g., GM-CSF) [3][8][17].
Surgical intervention: Critical for localized disease to remove necrotic tissue [9][15].
Categories: rare infectious diseases
Research Papers
2,185 drug discovery papers about Zygomycosis, with 29 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,185 drug discovery papers about Zygomycosis, with 29 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-12 | "Adjunctive topical amphotericin B in post-transplant surgical-site mucormycosis in an immunocompromised diabetic patient: a case report".
Cutaneous mucormycosis is a rapidly progressive and often fatal fungal infection predominantly affecting immunocompromised hosts, with post-transplant patients being particularly vulnerable due to immunosuppressive regimens and metabolic derangements. Despite its high mortality, especially in the context of surgical-site involvement, optimal therapeutic strategies remain underexplored. We present a rare case of surgical-site mucormycosis in a renal transplant recipient with poorly controlled diabetes, successfully managed using adjunctive topical antifungal therapy, highlighting a potential treatment strategy in immunosuppressed populations. A middle-aged male with chronic kidney disease, recent renal transplantation, and persistent hyperglycemia developed a non-healing surgical-site wound. Early clinical suspicion led to a bedside potassium hydroxide mount and expedited fungal cultures, which revealed mucormycosis. The patient was promptly initiated on systemic liposomal amphotericin B and, uniquely, adjunctive topical amphotericin B applied directly to the wound bed. Despite the challenges of ongoing immunosuppression, renal dysfunction, and glycemic instability, the patient demonstrated significant local and systemic improvement without the need for disfiguring surgical debridement. This case underscores the diagnostic value of bedside fungal microscopy in resource-limited and time-sensitive settings, where conventional culture and histopathology may be delayed. The clinical decision to incorporate topical amphotericin B, an underutilized yet mechanistically sound adjunct, was based on the rationale of high local fungal burden, systemic drug toxicity concerns, and limited evidence in immunosuppressed surgical cohorts. This approach not only curtailed disease progression but also preserved graft integrity and patient quality of life. This case highlights the under-recognition of mucormycosis in post-transplant surgical wounds and the absence of standardized topical antifungal protocols, representing a critical gap in transplant infectious disease management. This case report highlights that early bedside diagnosis, combined with individualized adjunctive topical amphotericin B, may help control post-transplant surgical-site mucormycosis, reduce the need for morbid surgical interventions, and warrants further evaluation for incorporation into future treatment guidelines for high-risk immunocompromised patients.
2026-08-12 | Three consecutive cases of rhinocerebral mucormycosis in calves caused by Lichtheimia ramosa infection on a beef cattle farm.
Three Japanese Black calves died within a two-month period on a beef cattle farm. Necropsy consistently revealed liquefactive necrosis of the ventral brain (extending from the olfactory bulb to the midbrain) and thymic atrophy. Histopathologically, necrosuppurative encephalitis characterized by abundant fungal hyphae was observed in all three cases. Fungal lesions also involved the olfactory mucosa, olfactory nerves, and olfactory bulb. Fungi isolated from the cerebrum of all three calves were identified as Lichtheimia ramosa. These cases were diagnosed as rhinocerebral mucormycosis, originating in the olfactory mucosa and extending to the cerebrum. Although mucormycosis is typically sporadic, this report documents the first occurrence of consecutive cases of bovine rhinocerebral mucormycosis caused by L. ramosa.
2026-08-07 | Gastrointestinal Mucormycosis Masquerading as an Abdominal Mass in an Immunocompetent Child.
We report a rare case of gastrointestinal mucormycosis (GI MM) in a 5-year-old immunocompetent child presenting as an abdominal mass. Initially misdiagnosed as an inflammatory myofibroblastic tumor, the correct diagnosis was made after a surgical resection via histopathology. Prompt antifungal therapy led to recovery. This case highlights atypical presentations of GI MM and the need for vigilance in seemingly immunocompetent patients.
2026-08-06 | Interpreting combined BALF-galactomannan and next-generation sequencing in pulmonary aspergillosis and mucormycosis: a two-center clinical decision framework.
To identify which patients with pulmonary aspergillosis or mucormycosis (PAM) derive the greatest incremental diagnostic benefit from next-generation sequencing (NGS) beyond conventional microbiology, and to derive a GM × NGS interpretive framework that identifies the patient subgroup in which NGS adds the most information, based on routinely available bedside variables. Secondary objectives were to characterize the pathogen spectrum detected by NGS, quantify pairwise concordance with BALF galactomannan and culture, and assess the relationship between quantitative Aspergillus reads and BALF-GM intensity. Two-center retrospective case-cohort study of 595 adults with NGS-tested pulmonary aspergillosis or mucormycosis (PAM; proven, probable, or possible per EORTC/MSGERC and ECMM-MSGERC criteria). Primary method-comparison analysis was restricted to the strict subset with NGS, BALF-galactomannan (GM), and culture all available (n = 434). Total Aspergillus reads were defined as the per-case sum of species-level Aspergillus reads parsed from free-text NGS reports, with Mucorales reads excluded. Multivariable logistic regression identified predictors of GM-negative status among NGS-positive cases (n = 353; complete-case n = 342). The prospective component was registered at the Chinese Clinical Trial Registry (ChiCTR2500099900). In the strict 434-case subset, NGS fungal-signal positivity was 81.3%, BALF-GM (≥0.8) 58.1%, and culture 43.1%; pairwise overlap was substantial but incomplete. The GM-negative/NGS-positive subgroup (n = 150) showed a milder phenotype than GM-positive/NGS-positive cases (severe pneumonia 28.7% (43/150) vs. 52.7% (107/203); mortality 6.7% (10/150) vs. 19.7% (40/203); both p < 0.001). Severe pneumonia was independently inversely associated with GM-negative status (adjusted OR 0.44, 95% CI 0.26-0.75, p = 0.002), while immunocompromise was independently positively associated (adjusted OR 2.01, 95% CI 1.17-3.47, p = 0.012). NGS Aspergillus positivity was essentially flat across BALF-GM intensity bands (79-82%); read counts correlated only weakly with BALF-GM titer [Spearman ρ = 0.185 (mNGS-only, n = 246)]. When BALF-GM and NGS are co-ordered on the same lavage in routine PAM workup, the four GM × NGS quadrants define distinct clinical phenotypes with concrete management implications: NGS positivity in GM-negative cases (34.6%) carries the highest incremental yield and a milder phenotype; conversely, a negative NGS in GM-positive cases must not be used to rule out severe PAM. Across quadrants, NGS adds species- and co-pathogen-level information that changes therapy.
2026-08-02 | Subcutaneous Zygomycosis Successfully Treated With Itraconazole Monotherapy: A Case Report From Central India.
Subcutaneous zygomycosis, also known as basidiobolomycosis, is a rare, chronic fungal infection that predominantly affects immunocompetent individuals in tropical and subtropical regions. The disease often presents as firm, painless, indurated subcutaneous swellings that may mimic malignancy, chronic bacterial infections, tuberculosis, or other deep fungal infections, leading to frequent misdiagnosis and unnecessary surgical interventions. We report the case of a 53-year-old immunocompetent man who presented with gradually enlarging, painless swellings over the right thigh and groin, accompanied by mild intermittent burning and pinprick pain for three months. There was no history of trauma or systemic illness. Examination revealed multiple firm, non-tender, indurated plaques with surface ulceration. Laboratory investigations were unremarkable. Histopathological examination of a wedge biopsy demonstrated dense eosinophilic granulomatous inflammation and broad, yeast-like fungal elements encased within an eosinophilic matrix (Splendore-Hoeppli phenomenon), confirming basidiobolomycosis. Fungal culture identified Basidiobolus ranarum. The patient was treated with suprabioavailable itraconazole at a dose of 65 mg twice daily. Marked clinical improvement was observed within one month, and complete resolution of the lesions occurred by five months, leaving minimal residual hyperpigmentation. No recurrence was noted during follow-up. This case highlights the importance of early biopsy and mycological evaluation in patients with chronic subcutaneous swellings to avoid misdiagnosis and unnecessary surgery. Itraconazole is an effective and well-tolerated therapy for subcutaneous zygomycosis, offering a nonsurgical treatment option. Early recognition and antifungal therapy can ensure excellent outcomes in this elusive infection.
antibodies
2026-05-25 | Cutaneous mucormycosis confirmed using a Mucorales-specific monoclonal antibody: a case study.
Mucormycosis is a highly aggressive and destructive angio-invasive infection caused by fungi of the order Mucorales. Diagnosis currently relies on lengthy and insensitive culture of biopsy specimens, as well as time-consuming histopathological examination of tissue samples, which lacks specificity. This case study describes an unusual presentation of cutaneous mucormycosis in an immunocompetent 49-year-old man following a traumatic farming injury to the hand. Despite appearing clinically well and having wounds that looked macroscopically clean after repeated debridement, the patient had a persistent infection caused by the Mucorales fungus, Lichtheimia ramosa. Diagnosis was delayed due to low clinical suspicion and routine homogenisation of biopsy samples, which reduced the sensitivity of conventional fungal culture and microscopy. Early surgical debridement combined with antifungal therapy was essential; however, treatment was complicated by amphotericin B-associated nephrotoxicity, necessitating a switch to posaconazole. The patient ultimately achieved wound healing with preserved hand function. The case demonstrates key challenges in diagnosing cutaneous mucormycosis, particularly in immunocompetent patients with environmentally contaminated wounds. The study highlights the need for improved awareness, optimal tissue handling, and more specific diagnostics for mucormycosis. We demonstrate the successful clinical use of a Mucorales-specific monoclonal antibody (mAb TG11), both as an immunohistochemistry stain and within a rapid lateral-flow device (LFD), to detect signature molecules of Mucorales infection in homogenised tissue samples, thereby improving the accuracy and speed of detection.
2026-05-25 | Dynamic Reprogramming of Fungal Cell Walls Underlies Germination and Immune Exposure in Zygomycetous Fungal Pathogens.
Fungal germination is a critical developmental transition that underlies environmental adaptation and pathogenicity, yet how the cell wall is molecularly reprogrammed during this process remains poorly understood. Here we show that germination of Rhizopus delemar involves a developmentally programmed transition from a β-1,3-glucan-rich dormant scaffold to a chitin-chitosan-dominated polarized wall. Using solid-state nuclear magnetic resonance spectroscopy and cytochemistry approaches, we show that resting conidia contains a rigid β-1,3-glucan- and chitosan-rich core beneath a persistent melanin layer. During swelling, this architecture is largely maintained, but germ tube emergence triggers complete shutdown of β-1,3-glucan synthesis and extensive chitin-chitosan enrichment. Distinct chitosan polymorphs are selectively enriched, while mobile polysaccharides are progressively incorporated into the rigid scaffold. This remodeling enhances neutrophil recognition of swollen and germinating conidia. Our study reveals a molecular mechanism linking fungal morphogenesis, cell wall remodeling, and morphotype-specific immune exposure during mucormycosis.
2026-05-22 | Emerging evidence for anti-PD-1 and IFN-γ as adjunctive immunotherapy in invasive mold infections.
Invasive mold diseases (IMDs) such as mucormycosis and aspergillosis carry high mortality despite optimal antifungal therapy. Adjunctive immunomodulation, including anti-PD-1 antibodies and interferon-γ, may help restore antifungal immunity in severely ill patients. We implemented multidisciplinary team meetings in France to assess and validate the use of adjunctive anti-PD-1 monoclonal antibodies and interferon-γ in combination with antifungal therapy for patients with life-threatening IMDs. Here, we report the characteristics and outcomes of the treated patients. Twelve cases were reviewed, and eight patients ultimately received adjunctive therapy. All presented with particularly severe IMDs, including seven mucormycosis (three cerebral, three intra-abdominal, and one extensive fasciitis) and one pulmonary aspergillosis. PD-1 expression on T cells was elevated in all patients. Following adjunctive treatment, six of the eight patients survived. Therapy was generally well tolerated; serious adverse events included one episode of cutaneous toxicity and two cases of acute respiratory distress syndrome, possibly related to immunotherapy. All resolved after treatment discontinuation. In our experience, adjunctive immunotherapy combined with antifungals was mostly associated with favorable outcomes in severe, refractory IMDs. These findings support further investigation of host-directed strategies as potential adjuncts in managing life-threatening fungal diseases. This study provides preliminary evidence supporting the clinical relevance of host-directed immunotherapy as an adjunct to antifungal treatment in severe invasive mold diseases (IMDs), which remain associated with high mortality despite optimized antifungal regimens. By targeting immune dysfunction, particularly T-cell exhaustion mediated through the PD-1 pathway, the combined use of anti-PD-1 monoclonal antibodies and interferon-γ aims to restore effective antifungal immune responses. The observed survival benefit in this small cohort supports the biological rationale that reversing immune paralysis can enhance pathogen clearance in patients with IMDs. Although limited by sample size, this work provides encouraging evidence supporting the feasibility, tolerability, and potential efficacy of combined immunomodulatory strategies, thereby contributing to the evolving paradigm of personalized and immune-guided management in IMDs. Future work should focus on biomarker-guided patient selection, rigorous monitoring, and determining the optimal timing for therapy initiation. Integrating immunological profiling into patient assessment may enable more precise, stratified therapeutic approaches.
2025-07-17 | Case Report: Immune checkpoint inhibitor exhibits dual benefits for a refractory lymphoma patient with disseminated mucormycosis.
Invasive mucormycosis contributes to a high mortality rate in patients with hematological malignancies. When it disseminates to multiple organs, especially to the brain, the prognosis is extremely poor. The traditional antifungal strategies including surgery have less efficacy in patients with hematological malignancies. Here, we describe a case report of a 62-year-old man with refractory lymphoma who developed mucormycosis caused by Rhizomucor pusillus after chemotherapy, which disseminated extensively to the lungs, diaphragm, brain and spleen. He was successfully treated with antifungal agents combined with PD-1 inhibitor, which may simultaneously exhibit efficacy in treatment of lymphoma and mucormycosis. The patient's lymphoma and mucormycosis were well controlled; ultimately, autologous hematopoietic stem cell transplantation was successfully performed, and the patient achieved long-term survival.
2025-07-14 | Early adjunct anti-PD-L1 immunotherapy improves outcomes and restores infection-induced immune paralysis in mice with invasive pulmonary mucormycosis.
Invasive pulmonary mucormycosis (IPM) is a severe opportunistic mold infection whose outcome is predominantly host driven. Preclinical proof-of-concept studies and clinical case reports in salvage therapy settings suggested a benefit of immune checkpoint inhibitors (ICIs) in IPM management. However, the kinetics of infection-induced immune paralysis and optimal timing of ICI therapy remain poorly understood. Here, we performed sequential nCounter-based transcriptomics on lung tissue of cyclophosphamide-immunosuppressed mice with IPM (Rhizopus arrhizus infection) to dynamically study the pulmonary immune environment. Within 7 days after infection, lungs of mice with IPM showed reversal of early proinflammatory signaling, impaired T-cell signaling, and upregulation of exhaustion markers. Similar immune paralysis signatures were seen in mice with invasive pulmonary aspergillosis and fusariosis. For therapeutic studies, Mucorales-active antifungal therapy with isavuconazonium sulfate (ISAV) was initiated on day 3 after IPM infection, along with anti-PD-L1 or a non-targeting isotype antibody (control) given either on days 3+5 (early) or days 6+8 (late). Both early and late adjunct anti-PD-L1 therapy were well-tolerated and significantly improved morbidity/mortality outcomes compared to ISAV + isotype. Notably, early adjunct anti-PD-L1 therapy promoted significantly stronger innate immune cell activation, upregulation of key cytokine pathways, reinvigoration of T-helper-cell signaling, and reversal of IPM-induced exhaustion signals than both late adjunct anti-PD-L1 and isotype control. These findings indicate that combined antifungal and early immunomodulatory therapy may be an important strategy to intercept immune paralysis and improve outcomes in immunocompromised hosts with IPM, inviting further preclinical and clinical exploration of early host-directed interventions to treat deadly mold pneumonias.
proteins
2026-03-02 | Transcriptomic and proteomic profiling of pulmonary mucormycosis reveals a failed activation of host immune response.
Mucormycosis is one of the most life-threatening fungal infections with delayed diagnosis and limited antifungal treatments. The transcriptome and proteome of pulmonary mucormycosis have not been fully investigated. We obtained lung tissues and paired controls from five pulmonary mucormycosis patients and utilized transcriptomic and proteomic approaches to explore host immune response during pulmonary mucormycosis. Our transcriptomic analysis found a number of up-regulated genes and pathways associated with immune defense. These genes were related to iron metabolism, pattern recognition receptors (PRRs), cytokines, chemokines et al., which enriched in pathways involved in both innate and adaptive immunity. However, proteomic profiling revealed limited upregulation of immune-related proteins and global suppression of pathways associated with host defense, especially those related to cell junction and cytoskeletal dynamics, indicating a failed activation of host immune response. Given the findings of compromised immune function at infection sites, enhancing adjuvant immunotherapy and intensifying localized antifungal treatments may be beneficial for this refractory infection. Our study firstly investigated the immune landscape in pulmonary mucormycosis through combined transcriptomic and proteomic profiling, which could provide novel mechanistic insights for the prevention and treatment of pulmonary mucormycosis.
2026-01-08 | Albumin orchestrates a natural host defence mechanism against mucormycosis.
Mucormycosis is an emerging, life-threatening human infection caused by Mucorales fungi1-3. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis through poorly understood mechanisms1,2,4,5, suggesting that uncharacterized host metabolic effectors may confer protective immunity against this infection. Here we uncover a master regulatory role of albumin in host defence against Mucorales through the modulation of fungal pathogenicity. Our initial studies identified severe hypoalb uminaemia as a prominent metabolic abnormality and an independent biomarker of poor mucormycosis outcome across three distinct cohorts of patients with mucormycosis. Notably, purified albumin selectively inhibits Mucorales growth among a range of pathogens, and albumin-deficient mice display susceptibility specifically to mucormycosis. The antifungal activity of albumin is mediated by the release of bound free fatty acids (FFAs). Albumin prevents FFA oxidation, which otherwise abolishes their antifungal properties, and sera from patients with mucormycosis display high levels of oxidized FFAs. Physiologically, albumin-bound FFAs suppress the expression of key virulence factors by inhibiting protein synthesis, the reby rendering Mucorales avirulent in vivo. Overall, we identify a host defence mechanism that directs the pathogen to suppress its pathogenicity program in response to unfavourable metabolic cues regulated by albumin. These findings have major implications for the pathogenesis and management of mucormycosis.
2025-06-25 | Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.
Writing with the perspective of a mentor, friend, and colleague, I am elated to contribute to this commemorative issue of the Journal of Fungi, which is dedicated to the landmark contributions of Dr. Dimitrios P. Kontoyiannis, who has greatly advanced our understanding of the epidemiology, pathogenesis, diagnosis, and treatment of mucormycosis. Through his efforts and leadership, the four pillars in the management of mucormycosis have been made much stronger: early diagnosis, the rapid initiation of antifungal therapy, augmentation of the host's defenses, and surgical intervention.
2024-12-16 | Albumin orchestrates a natural host defense mechanism against mucormycosis.
Mucormycosis is an emerging, life-threatening human infection caused by fungi of the order Mucorales. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis via poorly understood mechanisms. Therefore, it is highly likely that uncharacterized host metabolic effectors confer protective immunity against mucormycosis. Here, we uncover a master regulatory role of albumin in host defense against Mucorales through the modulation of the fungal pathogenicity program. Our initial studies identified severe hypoalbuminemia as a prominent metabolic abnormality and a biomarker of poor outcome in independent cohorts of mucormycosis patients. Strikingly, we found that purified albumin selectively inhibits Mucorales growth among a range of human pathogens, and albumin-deficient mice display susceptibility specifically to mucormycosis. The antifungal activity of albumin is mediated by the release of bound free fatty acids (FFAs). Importantly, albumin prevents FFA oxidation, which results in loss of their antifungal properties. A high degree of FFA oxidation is found in the sera of patients with mucormycosis. Physiologically, albumin-bound FFAs blocks the expression of the mycotoxin mucoricin and renders Mucorales avirulent in vivo. Overall, we discovered a novel host defense mechanism that directs the pathogen to suppress its growth and the expression of virulence factors in response to unfavorable metabolic cues regulated by albumin. These findings have major implications for the pathogenesis and management of mucormycosis.
2024-07-29 | Synergistic action of lactoferrin and its derived functional fragments as a promising therapeutic agent in combating mucormycosis.
Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales. Black fungus, or ‘mucormycosis’, is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.
cell therapies
2026-08-11 | Three-dimensional printed Patient-specific Implants for Reconstruction after Post-mucormycosis Maxillofacial Defects - A Systematic Review and Meta-analysis.
Post-mucormycosis maxillary, mid-facial and mandibular defects are often extensive, multi-planar and occur in medically compromised patients, making conventional obturators, free flaps and standard implant protocols challenging. Three-dimensional (3D)-printed patient-specific implants (PSIs) have emerged as a digitally planned, titanium-based alternative, but clinical evidence remains fragmented. A systematic search of electronic databases and manual sources was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. Studies reporting clinical outcomes of 3D-printed PSIs in patients with post-mucormycosis maxillary/mid-facial defects were included. Data on patient/defect characteristics, PSI design, complications, functional and aesthetic outcomes were extracted. Risk of bias was assessed using Joanna Briggs Institute checklists for cohort/case series and case reports. Eleven studies met the inclusion criteria. Defects were predominantly Brown Class II-III maxillectomy and complex mid-facial/orbital defects treated with computed tomography/cone-beam computed tomography-guided, additively manufactured titanium PSIs, often integrated with zygomatic anchorage. Pooled analysis of five multi-patient cohorts (n = 67) showed a PSI survival proportion of 0.96 (95% confidence interval = 0.91-1.00) at 6-24 months, with negligible heterogeneity (I 2 = 0%). Complications were mostly minor and true PSI loss was rare. Functional (mastication, speech and leakage control) and aesthetic outcomes, where reported, were generally favourable with high patient satisfaction. 3D-printed PSIs show excellent short-term survival and promising functional and aesthetic rehabilitation in extensive post-mucormycosis defects, but current evidence is limited to small, high-bias observational studies. Robust prospective and comparative research is needed before routine adoption can be recommended.
2026-08-11 | An innovative technique for facial deformity reconstruction following mucormycosis using three-dimensional printing: a case report.
Extensive destruction of the facial bones caused by mucormycosis poses a significant challenge for surgeons during the reconstruction phase. In this context, three-dimensional (3D) printing plays a pivotal role in the accurate planning and design of patient-specific implants tailored to the patient's deficient bone anatomy. A 52-year-old male patient presented with extensive destruction of the maxilla, zygomatic bones, and the floor of the nasal cavity secondary to mucormycosis. The patient was unable to phonate or swallow due to oronasal communication resulting from complete continuity between the oral and nasal cavities. Conventional reconstructive approaches typically require large volumes of autologous bone grafts, prolonged operative time, and multiple surgical stages. Accordingly, reconstruction using 3D printing technology with patient-specific titanium implants was employed. Reconstruction with a 3D-printed, patient-specific titanium implant yielded a satisfactory outcome within a single surgical procedure and a relatively short operative time. Furthermore, precise 3D planning facilitated subsequent dental rehabilitation.
2026-06-25 | Can Patients with Hematologic Disease and Prior Mucormycosis Undergo Stem Cell Transplantation?
The prognosis of mucormycosis after hematopoietic stem cell transplantation (HSCT) is generally poor but data on post-HSCT outcomes in patients with pre-HSCT mucormycosis are limited. We reviewed patients with documented mucormycosis at MD Anderson Cancer Center (2008-2024) and identified five patients who subsequently underwent HSCT. A literature review identified 24 additional such cases. Most patients had acute myeloid leukemia (69%). The most common site of mucormycosis was pulmonary (59%), while 31% had disseminated mucormycosis. All patients received antifungals and 76% had surgery prior to HSCT. At the time of HSCT, 67% had mucormycosis responding to treatment. No patient went to transplant with progressing mucormycosis. Eighty percent of patients with ≥12 months of follow-up after HSCT were alive. Five of the twenty-nine patients (17%) had documented or suspected mucormycosis recurrence post-HSCT. Relapsed malignancy pre-HSCT was associated with increased 12-month post-HSCT mortality (p = 0.031). Furthermore, post-transplant mortality was higher in cord blood recipients (p = 0.019) and tended to be higher in patients not undergoing surgery pre-HSCT (p = 0.062). Despite publication bias, our data suggest that HSCT can be conducted safely in selected patients with pre-HSCT mucormycosis, particularly when underlying hematologic malignancy is in remission, mucormycosis is stable, and surgical source control is feasible.
2025-08-11 | Successful Allogeneic Stem Cell Transplant for Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia After Pneumonectomy for Pulmonary Mucormycosis: A Case Report and Review of the Literature.
The incidence of relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia in adults is estimated to be 40%-50%. Allogeneic stem cell transplantation can improve survival in relapsed acute lymphoblastic leukemia; however, impaired pulmonary function is detrimental for surviving the transplantation process. Here, we present a successful case of allogeneic transplantation for relapsed B-acute lymphoblastic leukemia after total resection of the left lung due to angioinvasive pulmonary mucormycosis. To our knowledge, this is the first successful case of allogeneic transplantation after total pneumonectomy. Specific considerations in this case included careful donor selection, judicious choice of pre-transplantation conditioning regimen, and utilizing novel immunotherapies to ensure major residual disease negativity prior to transplant. It is our hope that this case provides additional guidance to clinicians caring for patients with hematologic malignancies who develop invasive fungal infections and require major lung surgeries.
2025-08-04 | Customised Patient-Specific Implants in Maxillofacial Reconstruction After Mucormycosis: A Case Series.
Patient-specific implants(psi) manufactured using 3D printing and CAD-CAM technology have played a major role in the rehabilitation of complex maxillofacial defects caused due to mucormycosis also known as the black fungus, which is a rare fungal infection that originates as a result of inhalation of its filamentous hyphal form. In this unique case series, we report six cases of complex maxillofacial defects caused due to mucormycosis managed by patient-specific implants, in Hyderabad. These patients had undergone either partial or total maxillectomy after being affected by mucormycosis and were disease-free clinically and radiographically for 6 or more months post-resection and were rehabilitated using patient-specific zygoma implants. All the implants and designs were standardized to achieve optimal functionality. The dental implant component was integrated into the PSI to achieve immediate postoperative dental rehabilitation. This case series shows a new era of reconstruction other than the old standardised method of using allografts for reconstruction in the maxillofacial region.
other
2026-07-29 | Understanding the biology of mucormycosis using contemporary omics tools: a review.
Mucormycosis (the "black fungus infection") is a life-threatening angioinvasive fungal infection caused by opportunistic fungi of the class Mucormycetes. A lot of clinical exercises were made in the post-coronavirus disease 2019 period due to admission of patients suffering from so called "black fungus disease". Many of patients had been operated for excision of their vital organs, colonized with massive fungal mycelia to restrict further invasion. In these circumstances, this apt article endeavour to scrutinize and debate some of the viable factors and prospective mechanisms that can assist to understand and elucidate the enigma of sudden, steep and deadly upsurge of mucormycosis infection. Here we review the specific contribution of high-throughput next-generation sequencing and multi-omics-based approaches to the general knowledge and understanding of Mucormycetes and further detail about the most exciting discoveries pertaining to the recently identified genetic advancements in Mucormycetes and mucormycosis. Through the use of a few genetic study models virulence factors in Mucormycetes that were previously unknown have been identified. Most remarkably, new research has opened up new possibilities for developing novel treatments against mucormycosis by identifying novel genes and process governing the pathogenic potential of Mucormycetes and their interaction with host. Ultimately virulence investigations in Mucormycetes that were previously hindered are now possible with new study models indicating a promising future for the field leading to the development of therapies to treat mucormycosis.
2026-01-02 | A BRCT domain-containing protein induced in early phagocytosis plays a crucial role in the pathogenesis of the mucoralean Rhizopus microsporus.
Mucormycosis, caused by mucoralean fungi, is among the most lethal fungal diseases, and a deeper understanding of its pathogenesis is urgently needed. Transcriptomic profiling of virulent strain (WT) and an RNAi-deficient strain (r3b2Δ) of M. lusitanicus during phagocytosis uncovered thousands of differentially expressed genes (DEGs), highlighting early metabolic activation as a key survival strategy inside the phagosome. Enriched pathways included amino acid transport, nucleotide metabolism, and translation, reflecting an adaptive fungal response to nutrient deprivation and host immune stress. Integrative analyses of mRNA and sRNA profiles also revealed a critical role of the RNAi pathways in modulating gene expression during infection. Building on these observations, we identified four chromatin- and transcription-related candidate virulence genes, brca1, box, hist1, and hda10, which were strongly upregulated during phagocytosis and regulated by RNAi. Functional disruption of their orthologs in the clinically relevant pathogen R. microsporus significantly reduced virulence in healthy mice, particularly in the brca1, hda1, and hist1 mutants. The brca1 knockout mutant also exhibited lower fungal burden in the brain and lungs and reduced survival rates after exposure to peritoneal immune cells. In contrast, their deletion in M. lusitanicus had no detectable impact on virulence in healthy animal models, highlighting species-dependent differences in pathogenic potential. These results demonstrate that M. lusitanicus is a valuable genetic model. However, combining studies across multiple Mucorales species is essential to uncover both conserved and species-specific mechanisms of host adaptation and virulence. These insights contribute to a broader understanding of fungal adaptation, immune evasion, and the identification of novel targets for antifungal intervention.
2025-03-07 | Heterotrimeric G-gamma 1 (Gpg1) participates with G-beta 1 (Gpb1) in the induction of hyphal growth and virulence via the PKA pathway in Mucor lusitanicus.
Previous work from our lab indicates that the heterotrimeric Gβ subunit 1 (Gpb1) enhances hyphal development and virulence in Mucor lusitanicus. In this study, three Gγ- and two additional Gβ-encoding genes were deleted to identify which ones might have a similar role as Gpb1. Deletion of gpg1 reduces hyphal growth, virulence, cyclic adenosine monophosphate (cAMP) levels, and protein kinase A (PKA) activity, similar to gpb1 deletion, suggesting that gpg1 participates in the same regulatory pathway as gpb1. The defects observed in Δgpg1 or Δgpb1 were suppressed by overexpression of the gene pkaR1 encoding the regulatory subunit 1 of PKA, indicating that this pathway is controlled by Gpg1 and Gpb1. Moreover, Δgpg1 and Δgpb1 show a downregulation of the transcription factors tec1 and tec2. Furthermore, tec-overexpression in Δgpg1, Δgpb1, and ΔpkaR1 restores the wild-type phenotype, indicating that both Tec are under control by the Gpb1, Gpg1, and PKA pathway. Moreover, the Δgpb1/Δgbg1(+)(-) exhibits lower aerobic germination, hyphal growth and downregulates NAD+-glutamate dehydrogenases (gdh2a/b), whereas virulence is similar to that of the wild-type (WT) strain. These alterations in Δgpb1/Δgbg1(+)(-) were reversed by the presence of glutamate during growth, suggesting that NAD+-Gdh2 could be under control of these subunits. Compared to the WT and Δgpb1/Δgbg1(+)(-) strains under aerobic growth, single deletion strains showed lower rhizoferrin levels, respiration and reactive oxygen species levels. Our results suggest that Gpg1 interacts with Gpb1 to positively control the hyphal development and virulence by repressing the PKA pathway, thereby regulating the mitochondrial oxidative metabolism in M. lusitanicus.
2024-09-10 | The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.
In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.
2024-08-28 | New lineages of RNA viruses from clinical isolates of Rhizopus microsporus revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis.
Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future.IMPORTANCEThe diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species Rhizopus microsporus. Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in R. microsporus. Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options.
small molecules
2026-08-12 | "Adjunctive topical amphotericin B in post-transplant surgical-site mucormycosis in an immunocompromised diabetic patient: a case report".
Cutaneous mucormycosis is a rapidly progressive and often fatal fungal infection predominantly affecting immunocompromised hosts, with post-transplant patients being particularly vulnerable due to immunosuppressive regimens and metabolic derangements. Despite its high mortality, especially in the context of surgical-site involvement, optimal therapeutic strategies remain underexplored. We present a rare case of surgical-site mucormycosis in a renal transplant recipient with poorly controlled diabetes, successfully managed using adjunctive topical antifungal therapy, highlighting a potential treatment strategy in immunosuppressed populations. A middle-aged male with chronic kidney disease, recent renal transplantation, and persistent hyperglycemia developed a non-healing surgical-site wound. Early clinical suspicion led to a bedside potassium hydroxide mount and expedited fungal cultures, which revealed mucormycosis. The patient was promptly initiated on systemic liposomal amphotericin B and, uniquely, adjunctive topical amphotericin B applied directly to the wound bed. Despite the challenges of ongoing immunosuppression, renal dysfunction, and glycemic instability, the patient demonstrated significant local and systemic improvement without the need for disfiguring surgical debridement. This case underscores the diagnostic value of bedside fungal microscopy in resource-limited and time-sensitive settings, where conventional culture and histopathology may be delayed. The clinical decision to incorporate topical amphotericin B, an underutilized yet mechanistically sound adjunct, was based on the rationale of high local fungal burden, systemic drug toxicity concerns, and limited evidence in immunosuppressed surgical cohorts. This approach not only curtailed disease progression but also preserved graft integrity and patient quality of life. This case highlights the under-recognition of mucormycosis in post-transplant surgical wounds and the absence of standardized topical antifungal protocols, representing a critical gap in transplant infectious disease management. This case report highlights that early bedside diagnosis, combined with individualized adjunctive topical amphotericin B, may help control post-transplant surgical-site mucormycosis, reduce the need for morbid surgical interventions, and warrants further evaluation for incorporation into future treatment guidelines for high-risk immunocompromised patients.
2026-08-12 | Three consecutive cases of rhinocerebral mucormycosis in calves caused by Lichtheimia ramosa infection on a beef cattle farm.
Three Japanese Black calves died within a two-month period on a beef cattle farm. Necropsy consistently revealed liquefactive necrosis of the ventral brain (extending from the olfactory bulb to the midbrain) and thymic atrophy. Histopathologically, necrosuppurative encephalitis characterized by abundant fungal hyphae was observed in all three cases. Fungal lesions also involved the olfactory mucosa, olfactory nerves, and olfactory bulb. Fungi isolated from the cerebrum of all three calves were identified as Lichtheimia ramosa. These cases were diagnosed as rhinocerebral mucormycosis, originating in the olfactory mucosa and extending to the cerebrum. Although mucormycosis is typically sporadic, this report documents the first occurrence of consecutive cases of bovine rhinocerebral mucormycosis caused by L. ramosa.
2026-08-07 | Gastrointestinal Mucormycosis Masquerading as an Abdominal Mass in an Immunocompetent Child.
We report a rare case of gastrointestinal mucormycosis (GI MM) in a 5-year-old immunocompetent child presenting as an abdominal mass. Initially misdiagnosed as an inflammatory myofibroblastic tumor, the correct diagnosis was made after a surgical resection via histopathology. Prompt antifungal therapy led to recovery. This case highlights atypical presentations of GI MM and the need for vigilance in seemingly immunocompetent patients.
2026-08-06 | Interpreting combined BALF-galactomannan and next-generation sequencing in pulmonary aspergillosis and mucormycosis: a two-center clinical decision framework.
To identify which patients with pulmonary aspergillosis or mucormycosis (PAM) derive the greatest incremental diagnostic benefit from next-generation sequencing (NGS) beyond conventional microbiology, and to derive a GM × NGS interpretive framework that identifies the patient subgroup in which NGS adds the most information, based on routinely available bedside variables. Secondary objectives were to characterize the pathogen spectrum detected by NGS, quantify pairwise concordance with BALF galactomannan and culture, and assess the relationship between quantitative Aspergillus reads and BALF-GM intensity. Two-center retrospective case-cohort study of 595 adults with NGS-tested pulmonary aspergillosis or mucormycosis (PAM; proven, probable, or possible per EORTC/MSGERC and ECMM-MSGERC criteria). Primary method-comparison analysis was restricted to the strict subset with NGS, BALF-galactomannan (GM), and culture all available (n = 434). Total Aspergillus reads were defined as the per-case sum of species-level Aspergillus reads parsed from free-text NGS reports, with Mucorales reads excluded. Multivariable logistic regression identified predictors of GM-negative status among NGS-positive cases (n = 353; complete-case n = 342). The prospective component was registered at the Chinese Clinical Trial Registry (ChiCTR2500099900). In the strict 434-case subset, NGS fungal-signal positivity was 81.3%, BALF-GM (≥0.8) 58.1%, and culture 43.1%; pairwise overlap was substantial but incomplete. The GM-negative/NGS-positive subgroup (n = 150) showed a milder phenotype than GM-positive/NGS-positive cases (severe pneumonia 28.7% (43/150) vs. 52.7% (107/203); mortality 6.7% (10/150) vs. 19.7% (40/203); both p < 0.001). Severe pneumonia was independently inversely associated with GM-negative status (adjusted OR 0.44, 95% CI 0.26-0.75, p = 0.002), while immunocompromise was independently positively associated (adjusted OR 2.01, 95% CI 1.17-3.47, p = 0.012). NGS Aspergillus positivity was essentially flat across BALF-GM intensity bands (79-82%); read counts correlated only weakly with BALF-GM titer [Spearman ρ = 0.185 (mNGS-only, n = 246)]. When BALF-GM and NGS are co-ordered on the same lavage in routine PAM workup, the four GM × NGS quadrants define distinct clinical phenotypes with concrete management implications: NGS positivity in GM-negative cases (34.6%) carries the highest incremental yield and a milder phenotype; conversely, a negative NGS in GM-positive cases must not be used to rule out severe PAM. Across quadrants, NGS adds species- and co-pathogen-level information that changes therapy.
2026-08-02 | Subcutaneous Zygomycosis Successfully Treated With Itraconazole Monotherapy: A Case Report From Central India.
Subcutaneous zygomycosis, also known as basidiobolomycosis, is a rare, chronic fungal infection that predominantly affects immunocompetent individuals in tropical and subtropical regions. The disease often presents as firm, painless, indurated subcutaneous swellings that may mimic malignancy, chronic bacterial infections, tuberculosis, or other deep fungal infections, leading to frequent misdiagnosis and unnecessary surgical interventions. We report the case of a 53-year-old immunocompetent man who presented with gradually enlarging, painless swellings over the right thigh and groin, accompanied by mild intermittent burning and pinprick pain for three months. There was no history of trauma or systemic illness. Examination revealed multiple firm, non-tender, indurated plaques with surface ulceration. Laboratory investigations were unremarkable. Histopathological examination of a wedge biopsy demonstrated dense eosinophilic granulomatous inflammation and broad, yeast-like fungal elements encased within an eosinophilic matrix (Splendore-Hoeppli phenomenon), confirming basidiobolomycosis. Fungal culture identified Basidiobolus ranarum. The patient was treated with suprabioavailable itraconazole at a dose of 65 mg twice daily. Marked clinical improvement was observed within one month, and complete resolution of the lesions occurred by five months, leaving minimal residual hyperpigmentation. No recurrence was noted during follow-up. This case highlights the importance of early biopsy and mycological evaluation in patients with chronic subcutaneous swellings to avoid misdiagnosis and unnecessary surgery. Itraconazole is an effective and well-tolerated therapy for subcutaneous zygomycosis, offering a nonsurgical treatment option. Early recognition and antifungal therapy can ensure excellent outcomes in this elusive infection.
antibodies
2026-05-25 | Cutaneous mucormycosis confirmed using a Mucorales-specific monoclonal antibody: a case study.
Mucormycosis is a highly aggressive and destructive angio-invasive infection caused by fungi of the order Mucorales. Diagnosis currently relies on lengthy and insensitive culture of biopsy specimens, as well as time-consuming histopathological examination of tissue samples, which lacks specificity. This case study describes an unusual presentation of cutaneous mucormycosis in an immunocompetent 49-year-old man following a traumatic farming injury to the hand. Despite appearing clinically well and having wounds that looked macroscopically clean after repeated debridement, the patient had a persistent infection caused by the Mucorales fungus, Lichtheimia ramosa. Diagnosis was delayed due to low clinical suspicion and routine homogenisation of biopsy samples, which reduced the sensitivity of conventional fungal culture and microscopy. Early surgical debridement combined with antifungal therapy was essential; however, treatment was complicated by amphotericin B-associated nephrotoxicity, necessitating a switch to posaconazole. The patient ultimately achieved wound healing with preserved hand function. The case demonstrates key challenges in diagnosing cutaneous mucormycosis, particularly in immunocompetent patients with environmentally contaminated wounds. The study highlights the need for improved awareness, optimal tissue handling, and more specific diagnostics for mucormycosis. We demonstrate the successful clinical use of a Mucorales-specific monoclonal antibody (mAb TG11), both as an immunohistochemistry stain and within a rapid lateral-flow device (LFD), to detect signature molecules of Mucorales infection in homogenised tissue samples, thereby improving the accuracy and speed of detection.
2026-05-25 | Dynamic Reprogramming of Fungal Cell Walls Underlies Germination and Immune Exposure in Zygomycetous Fungal Pathogens.
Fungal germination is a critical developmental transition that underlies environmental adaptation and pathogenicity, yet how the cell wall is molecularly reprogrammed during this process remains poorly understood. Here we show that germination of Rhizopus delemar involves a developmentally programmed transition from a β-1,3-glucan-rich dormant scaffold to a chitin-chitosan-dominated polarized wall. Using solid-state nuclear magnetic resonance spectroscopy and cytochemistry approaches, we show that resting conidia contains a rigid β-1,3-glucan- and chitosan-rich core beneath a persistent melanin layer. During swelling, this architecture is largely maintained, but germ tube emergence triggers complete shutdown of β-1,3-glucan synthesis and extensive chitin-chitosan enrichment. Distinct chitosan polymorphs are selectively enriched, while mobile polysaccharides are progressively incorporated into the rigid scaffold. This remodeling enhances neutrophil recognition of swollen and germinating conidia. Our study reveals a molecular mechanism linking fungal morphogenesis, cell wall remodeling, and morphotype-specific immune exposure during mucormycosis.
2026-05-22 | Emerging evidence for anti-PD-1 and IFN-γ as adjunctive immunotherapy in invasive mold infections.
Invasive mold diseases (IMDs) such as mucormycosis and aspergillosis carry high mortality despite optimal antifungal therapy. Adjunctive immunomodulation, including anti-PD-1 antibodies and interferon-γ, may help restore antifungal immunity in severely ill patients. We implemented multidisciplinary team meetings in France to assess and validate the use of adjunctive anti-PD-1 monoclonal antibodies and interferon-γ in combination with antifungal therapy for patients with life-threatening IMDs. Here, we report the characteristics and outcomes of the treated patients. Twelve cases were reviewed, and eight patients ultimately received adjunctive therapy. All presented with particularly severe IMDs, including seven mucormycosis (three cerebral, three intra-abdominal, and one extensive fasciitis) and one pulmonary aspergillosis. PD-1 expression on T cells was elevated in all patients. Following adjunctive treatment, six of the eight patients survived. Therapy was generally well tolerated; serious adverse events included one episode of cutaneous toxicity and two cases of acute respiratory distress syndrome, possibly related to immunotherapy. All resolved after treatment discontinuation. In our experience, adjunctive immunotherapy combined with antifungals was mostly associated with favorable outcomes in severe, refractory IMDs. These findings support further investigation of host-directed strategies as potential adjuncts in managing life-threatening fungal diseases. This study provides preliminary evidence supporting the clinical relevance of host-directed immunotherapy as an adjunct to antifungal treatment in severe invasive mold diseases (IMDs), which remain associated with high mortality despite optimized antifungal regimens. By targeting immune dysfunction, particularly T-cell exhaustion mediated through the PD-1 pathway, the combined use of anti-PD-1 monoclonal antibodies and interferon-γ aims to restore effective antifungal immune responses. The observed survival benefit in this small cohort supports the biological rationale that reversing immune paralysis can enhance pathogen clearance in patients with IMDs. Although limited by sample size, this work provides encouraging evidence supporting the feasibility, tolerability, and potential efficacy of combined immunomodulatory strategies, thereby contributing to the evolving paradigm of personalized and immune-guided management in IMDs. Future work should focus on biomarker-guided patient selection, rigorous monitoring, and determining the optimal timing for therapy initiation. Integrating immunological profiling into patient assessment may enable more precise, stratified therapeutic approaches.
2025-07-17 | Case Report: Immune checkpoint inhibitor exhibits dual benefits for a refractory lymphoma patient with disseminated mucormycosis.
Invasive mucormycosis contributes to a high mortality rate in patients with hematological malignancies. When it disseminates to multiple organs, especially to the brain, the prognosis is extremely poor. The traditional antifungal strategies including surgery have less efficacy in patients with hematological malignancies. Here, we describe a case report of a 62-year-old man with refractory lymphoma who developed mucormycosis caused by Rhizomucor pusillus after chemotherapy, which disseminated extensively to the lungs, diaphragm, brain and spleen. He was successfully treated with antifungal agents combined with PD-1 inhibitor, which may simultaneously exhibit efficacy in treatment of lymphoma and mucormycosis. The patient's lymphoma and mucormycosis were well controlled; ultimately, autologous hematopoietic stem cell transplantation was successfully performed, and the patient achieved long-term survival.
2025-07-14 | Early adjunct anti-PD-L1 immunotherapy improves outcomes and restores infection-induced immune paralysis in mice with invasive pulmonary mucormycosis.
Invasive pulmonary mucormycosis (IPM) is a severe opportunistic mold infection whose outcome is predominantly host driven. Preclinical proof-of-concept studies and clinical case reports in salvage therapy settings suggested a benefit of immune checkpoint inhibitors (ICIs) in IPM management. However, the kinetics of infection-induced immune paralysis and optimal timing of ICI therapy remain poorly understood. Here, we performed sequential nCounter-based transcriptomics on lung tissue of cyclophosphamide-immunosuppressed mice with IPM (Rhizopus arrhizus infection) to dynamically study the pulmonary immune environment. Within 7 days after infection, lungs of mice with IPM showed reversal of early proinflammatory signaling, impaired T-cell signaling, and upregulation of exhaustion markers. Similar immune paralysis signatures were seen in mice with invasive pulmonary aspergillosis and fusariosis. For therapeutic studies, Mucorales-active antifungal therapy with isavuconazonium sulfate (ISAV) was initiated on day 3 after IPM infection, along with anti-PD-L1 or a non-targeting isotype antibody (control) given either on days 3+5 (early) or days 6+8 (late). Both early and late adjunct anti-PD-L1 therapy were well-tolerated and significantly improved morbidity/mortality outcomes compared to ISAV + isotype. Notably, early adjunct anti-PD-L1 therapy promoted significantly stronger innate immune cell activation, upregulation of key cytokine pathways, reinvigoration of T-helper-cell signaling, and reversal of IPM-induced exhaustion signals than both late adjunct anti-PD-L1 and isotype control. These findings indicate that combined antifungal and early immunomodulatory therapy may be an important strategy to intercept immune paralysis and improve outcomes in immunocompromised hosts with IPM, inviting further preclinical and clinical exploration of early host-directed interventions to treat deadly mold pneumonias.
proteins
2026-03-02 | Transcriptomic and proteomic profiling of pulmonary mucormycosis reveals a failed activation of host immune response.
Mucormycosis is one of the most life-threatening fungal infections with delayed diagnosis and limited antifungal treatments. The transcriptome and proteome of pulmonary mucormycosis have not been fully investigated. We obtained lung tissues and paired controls from five pulmonary mucormycosis patients and utilized transcriptomic and proteomic approaches to explore host immune response during pulmonary mucormycosis. Our transcriptomic analysis found a number of up-regulated genes and pathways associated with immune defense. These genes were related to iron metabolism, pattern recognition receptors (PRRs), cytokines, chemokines et al., which enriched in pathways involved in both innate and adaptive immunity. However, proteomic profiling revealed limited upregulation of immune-related proteins and global suppression of pathways associated with host defense, especially those related to cell junction and cytoskeletal dynamics, indicating a failed activation of host immune response. Given the findings of compromised immune function at infection sites, enhancing adjuvant immunotherapy and intensifying localized antifungal treatments may be beneficial for this refractory infection. Our study firstly investigated the immune landscape in pulmonary mucormycosis through combined transcriptomic and proteomic profiling, which could provide novel mechanistic insights for the prevention and treatment of pulmonary mucormycosis.
2026-01-08 | Albumin orchestrates a natural host defence mechanism against mucormycosis.
Mucormycosis is an emerging, life-threatening human infection caused by Mucorales fungi1-3. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis through poorly understood mechanisms1,2,4,5, suggesting that uncharacterized host metabolic effectors may confer protective immunity against this infection. Here we uncover a master regulatory role of albumin in host defence against Mucorales through the modulation of fungal pathogenicity. Our initial studies identified severe hypoalb uminaemia as a prominent metabolic abnormality and an independent biomarker of poor mucormycosis outcome across three distinct cohorts of patients with mucormycosis. Notably, purified albumin selectively inhibits Mucorales growth among a range of pathogens, and albumin-deficient mice display susceptibility specifically to mucormycosis. The antifungal activity of albumin is mediated by the release of bound free fatty acids (FFAs). Albumin prevents FFA oxidation, which otherwise abolishes their antifungal properties, and sera from patients with mucormycosis display high levels of oxidized FFAs. Physiologically, albumin-bound FFAs suppress the expression of key virulence factors by inhibiting protein synthesis, the reby rendering Mucorales avirulent in vivo. Overall, we identify a host defence mechanism that directs the pathogen to suppress its pathogenicity program in response to unfavourable metabolic cues regulated by albumin. These findings have major implications for the pathogenesis and management of mucormycosis.
2025-06-25 | Commemorating the Landmark Advances in Our Understanding of Mucormycosis by Dimitrios P. Kontoyiannis.
Writing with the perspective of a mentor, friend, and colleague, I am elated to contribute to this commemorative issue of the Journal of Fungi, which is dedicated to the landmark contributions of Dr. Dimitrios P. Kontoyiannis, who has greatly advanced our understanding of the epidemiology, pathogenesis, diagnosis, and treatment of mucormycosis. Through his efforts and leadership, the four pillars in the management of mucormycosis have been made much stronger: early diagnosis, the rapid initiation of antifungal therapy, augmentation of the host's defenses, and surgical intervention.
2024-12-16 | Albumin orchestrates a natural host defense mechanism against mucormycosis.
Mucormycosis is an emerging, life-threatening human infection caused by fungi of the order Mucorales. Metabolic disorders uniquely predispose an ever-expanding group of patients to mucormycosis via poorly understood mechanisms. Therefore, it is highly likely that uncharacterized host metabolic effectors confer protective immunity against mucormycosis. Here, we uncover a master regulatory role of albumin in host defense against Mucorales through the modulation of the fungal pathogenicity program. Our initial studies identified severe hypoalbuminemia as a prominent metabolic abnormality and a biomarker of poor outcome in independent cohorts of mucormycosis patients. Strikingly, we found that purified albumin selectively inhibits Mucorales growth among a range of human pathogens, and albumin-deficient mice display susceptibility specifically to mucormycosis. The antifungal activity of albumin is mediated by the release of bound free fatty acids (FFAs). Importantly, albumin prevents FFA oxidation, which results in loss of their antifungal properties. A high degree of FFA oxidation is found in the sera of patients with mucormycosis. Physiologically, albumin-bound FFAs blocks the expression of the mycotoxin mucoricin and renders Mucorales avirulent in vivo. Overall, we discovered a novel host defense mechanism that directs the pathogen to suppress its growth and the expression of virulence factors in response to unfavorable metabolic cues regulated by albumin. These findings have major implications for the pathogenesis and management of mucormycosis.
2024-07-29 | Synergistic action of lactoferrin and its derived functional fragments as a promising therapeutic agent in combating mucormycosis.
Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales. Black fungus, or ‘mucormycosis’, is a dangerous fungal infection. Normally, it affects people with a weakened immune system. It is only treatable when diagnosed early. It spreads by breathing the fungus in, eating contaminated food or direct contact with an infected wound. There are not many medicines that can treat this type of fungus, so it is important to find new ones. In this study, we tested a natural protein called lactoferrin and some of its building blocks, called peptides, to see if they could stop the fungus from growing. Lactoferrin and its peptides could stop the fungus from growing, especially when used with a medicine called amphotericin B. This means that lactoferrin could potentially be a helpful treatment for this fungal infection.
cell therapies
2026-08-11 | Three-dimensional printed Patient-specific Implants for Reconstruction after Post-mucormycosis Maxillofacial Defects - A Systematic Review and Meta-analysis.
Post-mucormycosis maxillary, mid-facial and mandibular defects are often extensive, multi-planar and occur in medically compromised patients, making conventional obturators, free flaps and standard implant protocols challenging. Three-dimensional (3D)-printed patient-specific implants (PSIs) have emerged as a digitally planned, titanium-based alternative, but clinical evidence remains fragmented. A systematic search of electronic databases and manual sources was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. Studies reporting clinical outcomes of 3D-printed PSIs in patients with post-mucormycosis maxillary/mid-facial defects were included. Data on patient/defect characteristics, PSI design, complications, functional and aesthetic outcomes were extracted. Risk of bias was assessed using Joanna Briggs Institute checklists for cohort/case series and case reports. Eleven studies met the inclusion criteria. Defects were predominantly Brown Class II-III maxillectomy and complex mid-facial/orbital defects treated with computed tomography/cone-beam computed tomography-guided, additively manufactured titanium PSIs, often integrated with zygomatic anchorage. Pooled analysis of five multi-patient cohorts (n = 67) showed a PSI survival proportion of 0.96 (95% confidence interval = 0.91-1.00) at 6-24 months, with negligible heterogeneity (I 2 = 0%). Complications were mostly minor and true PSI loss was rare. Functional (mastication, speech and leakage control) and aesthetic outcomes, where reported, were generally favourable with high patient satisfaction. 3D-printed PSIs show excellent short-term survival and promising functional and aesthetic rehabilitation in extensive post-mucormycosis defects, but current evidence is limited to small, high-bias observational studies. Robust prospective and comparative research is needed before routine adoption can be recommended.
2026-08-11 | An innovative technique for facial deformity reconstruction following mucormycosis using three-dimensional printing: a case report.
Extensive destruction of the facial bones caused by mucormycosis poses a significant challenge for surgeons during the reconstruction phase. In this context, three-dimensional (3D) printing plays a pivotal role in the accurate planning and design of patient-specific implants tailored to the patient's deficient bone anatomy. A 52-year-old male patient presented with extensive destruction of the maxilla, zygomatic bones, and the floor of the nasal cavity secondary to mucormycosis. The patient was unable to phonate or swallow due to oronasal communication resulting from complete continuity between the oral and nasal cavities. Conventional reconstructive approaches typically require large volumes of autologous bone grafts, prolonged operative time, and multiple surgical stages. Accordingly, reconstruction using 3D printing technology with patient-specific titanium implants was employed. Reconstruction with a 3D-printed, patient-specific titanium implant yielded a satisfactory outcome within a single surgical procedure and a relatively short operative time. Furthermore, precise 3D planning facilitated subsequent dental rehabilitation.
2026-06-25 | Can Patients with Hematologic Disease and Prior Mucormycosis Undergo Stem Cell Transplantation?
The prognosis of mucormycosis after hematopoietic stem cell transplantation (HSCT) is generally poor but data on post-HSCT outcomes in patients with pre-HSCT mucormycosis are limited. We reviewed patients with documented mucormycosis at MD Anderson Cancer Center (2008-2024) and identified five patients who subsequently underwent HSCT. A literature review identified 24 additional such cases. Most patients had acute myeloid leukemia (69%). The most common site of mucormycosis was pulmonary (59%), while 31% had disseminated mucormycosis. All patients received antifungals and 76% had surgery prior to HSCT. At the time of HSCT, 67% had mucormycosis responding to treatment. No patient went to transplant with progressing mucormycosis. Eighty percent of patients with ≥12 months of follow-up after HSCT were alive. Five of the twenty-nine patients (17%) had documented or suspected mucormycosis recurrence post-HSCT. Relapsed malignancy pre-HSCT was associated with increased 12-month post-HSCT mortality (p = 0.031). Furthermore, post-transplant mortality was higher in cord blood recipients (p = 0.019) and tended to be higher in patients not undergoing surgery pre-HSCT (p = 0.062). Despite publication bias, our data suggest that HSCT can be conducted safely in selected patients with pre-HSCT mucormycosis, particularly when underlying hematologic malignancy is in remission, mucormycosis is stable, and surgical source control is feasible.
2025-08-11 | Successful Allogeneic Stem Cell Transplant for Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia After Pneumonectomy for Pulmonary Mucormycosis: A Case Report and Review of the Literature.
The incidence of relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia in adults is estimated to be 40%-50%. Allogeneic stem cell transplantation can improve survival in relapsed acute lymphoblastic leukemia; however, impaired pulmonary function is detrimental for surviving the transplantation process. Here, we present a successful case of allogeneic transplantation for relapsed B-acute lymphoblastic leukemia after total resection of the left lung due to angioinvasive pulmonary mucormycosis. To our knowledge, this is the first successful case of allogeneic transplantation after total pneumonectomy. Specific considerations in this case included careful donor selection, judicious choice of pre-transplantation conditioning regimen, and utilizing novel immunotherapies to ensure major residual disease negativity prior to transplant. It is our hope that this case provides additional guidance to clinicians caring for patients with hematologic malignancies who develop invasive fungal infections and require major lung surgeries.
2025-08-04 | Customised Patient-Specific Implants in Maxillofacial Reconstruction After Mucormycosis: A Case Series.
Patient-specific implants(psi) manufactured using 3D printing and CAD-CAM technology have played a major role in the rehabilitation of complex maxillofacial defects caused due to mucormycosis also known as the black fungus, which is a rare fungal infection that originates as a result of inhalation of its filamentous hyphal form. In this unique case series, we report six cases of complex maxillofacial defects caused due to mucormycosis managed by patient-specific implants, in Hyderabad. These patients had undergone either partial or total maxillectomy after being affected by mucormycosis and were disease-free clinically and radiographically for 6 or more months post-resection and were rehabilitated using patient-specific zygoma implants. All the implants and designs were standardized to achieve optimal functionality. The dental implant component was integrated into the PSI to achieve immediate postoperative dental rehabilitation. This case series shows a new era of reconstruction other than the old standardised method of using allografts for reconstruction in the maxillofacial region.
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2026-07-29 | Understanding the biology of mucormycosis using contemporary omics tools: a review.
Mucormycosis (the "black fungus infection") is a life-threatening angioinvasive fungal infection caused by opportunistic fungi of the class Mucormycetes. A lot of clinical exercises were made in the post-coronavirus disease 2019 period due to admission of patients suffering from so called "black fungus disease". Many of patients had been operated for excision of their vital organs, colonized with massive fungal mycelia to restrict further invasion. In these circumstances, this apt article endeavour to scrutinize and debate some of the viable factors and prospective mechanisms that can assist to understand and elucidate the enigma of sudden, steep and deadly upsurge of mucormycosis infection. Here we review the specific contribution of high-throughput next-generation sequencing and multi-omics-based approaches to the general knowledge and understanding of Mucormycetes and further detail about the most exciting discoveries pertaining to the recently identified genetic advancements in Mucormycetes and mucormycosis. Through the use of a few genetic study models virulence factors in Mucormycetes that were previously unknown have been identified. Most remarkably, new research has opened up new possibilities for developing novel treatments against mucormycosis by identifying novel genes and process governing the pathogenic potential of Mucormycetes and their interaction with host. Ultimately virulence investigations in Mucormycetes that were previously hindered are now possible with new study models indicating a promising future for the field leading to the development of therapies to treat mucormycosis.
2026-01-02 | A BRCT domain-containing protein induced in early phagocytosis plays a crucial role in the pathogenesis of the mucoralean Rhizopus microsporus.
Mucormycosis, caused by mucoralean fungi, is among the most lethal fungal diseases, and a deeper understanding of its pathogenesis is urgently needed. Transcriptomic profiling of virulent strain (WT) and an RNAi-deficient strain (r3b2Δ) of M. lusitanicus during phagocytosis uncovered thousands of differentially expressed genes (DEGs), highlighting early metabolic activation as a key survival strategy inside the phagosome. Enriched pathways included amino acid transport, nucleotide metabolism, and translation, reflecting an adaptive fungal response to nutrient deprivation and host immune stress. Integrative analyses of mRNA and sRNA profiles also revealed a critical role of the RNAi pathways in modulating gene expression during infection. Building on these observations, we identified four chromatin- and transcription-related candidate virulence genes, brca1, box, hist1, and hda10, which were strongly upregulated during phagocytosis and regulated by RNAi. Functional disruption of their orthologs in the clinically relevant pathogen R. microsporus significantly reduced virulence in healthy mice, particularly in the brca1, hda1, and hist1 mutants. The brca1 knockout mutant also exhibited lower fungal burden in the brain and lungs and reduced survival rates after exposure to peritoneal immune cells. In contrast, their deletion in M. lusitanicus had no detectable impact on virulence in healthy animal models, highlighting species-dependent differences in pathogenic potential. These results demonstrate that M. lusitanicus is a valuable genetic model. However, combining studies across multiple Mucorales species is essential to uncover both conserved and species-specific mechanisms of host adaptation and virulence. These insights contribute to a broader understanding of fungal adaptation, immune evasion, and the identification of novel targets for antifungal intervention.
2025-03-07 | Heterotrimeric G-gamma 1 (Gpg1) participates with G-beta 1 (Gpb1) in the induction of hyphal growth and virulence via the PKA pathway in Mucor lusitanicus.
Previous work from our lab indicates that the heterotrimeric Gβ subunit 1 (Gpb1) enhances hyphal development and virulence in Mucor lusitanicus. In this study, three Gγ- and two additional Gβ-encoding genes were deleted to identify which ones might have a similar role as Gpb1. Deletion of gpg1 reduces hyphal growth, virulence, cyclic adenosine monophosphate (cAMP) levels, and protein kinase A (PKA) activity, similar to gpb1 deletion, suggesting that gpg1 participates in the same regulatory pathway as gpb1. The defects observed in Δgpg1 or Δgpb1 were suppressed by overexpression of the gene pkaR1 encoding the regulatory subunit 1 of PKA, indicating that this pathway is controlled by Gpg1 and Gpb1. Moreover, Δgpg1 and Δgpb1 show a downregulation of the transcription factors tec1 and tec2. Furthermore, tec-overexpression in Δgpg1, Δgpb1, and ΔpkaR1 restores the wild-type phenotype, indicating that both Tec are under control by the Gpb1, Gpg1, and PKA pathway. Moreover, the Δgpb1/Δgbg1(+)(-) exhibits lower aerobic germination, hyphal growth and downregulates NAD+-glutamate dehydrogenases (gdh2a/b), whereas virulence is similar to that of the wild-type (WT) strain. These alterations in Δgpb1/Δgbg1(+)(-) were reversed by the presence of glutamate during growth, suggesting that NAD+-Gdh2 could be under control of these subunits. Compared to the WT and Δgpb1/Δgbg1(+)(-) strains under aerobic growth, single deletion strains showed lower rhizoferrin levels, respiration and reactive oxygen species levels. Our results suggest that Gpg1 interacts with Gpb1 to positively control the hyphal development and virulence by repressing the PKA pathway, thereby regulating the mitochondrial oxidative metabolism in M. lusitanicus.
2024-09-10 | The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.
In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.
2024-08-28 | New lineages of RNA viruses from clinical isolates of Rhizopus microsporus revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis.
Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future.IMPORTANCEThe diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species Rhizopus microsporus. Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in R. microsporus. Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options.
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Drug Discovery Landscape
6 orphan drug designations for Zygomycosis, including 2 approved therapies.
6 orphan drug designations for Zygomycosis, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Fosmanogepix | small molecules | EMA | 2023-02-15 | — | Basilea Pharmaceutica Deutschland GmbH |
Posaconazole | small molecules | FDA | 2021-12-13 | — | AET Pharma US, Inc. |
Isavuconazonium sulfate [Cresemba] | small molecules | EMA | 2014-06-04 | 2015-10-19 | Basilea Pharmaceutica Deutschland GmbH |
isavuconazonium sulfate [Cresemba] | small molecules | FDA | 2013-10-25 | 2015-03-06 | Astellas Pharma Global Development Inc. |
posaconazole | small molecules | FDA | 2004-07-16 | — | Merck Sharp & Dohme LLC |
Amphotericin B lipid complex | small molecules | FDA | 1996-05-06 | — | The Liposome Company, Inc. |
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