Invasive Fungal Infections Research Articles

Hidden allies: how extracellular vesicles drive biofilm formation, stress adaptation, and host–immune interactions in human fungal pathogens

ABSTRACT Pathogenic fungi pose a significant threat to human health, especially given the rising incidence of invasive fungal infections and the emergence of drug-resistant strains. This requires the development of vaccines and the advancement of antifungal strategies. Recent studies have focused on the roles of fungal extracellular vesicles (EVs) in intercellular communication and host-pathogen interactions. EVs are nanosized, lipid membrane-bound particles that facilitate the transfer of proteins, lipids, and nucleic acids. Here, we review the multifaceted functions of EVs produced by different human fungal pathogens, highlighting their importance in the response of fungal cells to different environmental cues and their interactions with host immune cells. We summarize the current state of research on EVs and how leveraging this knowledge can lead to innovative approaches in vaccine development and antifungal treatment.

The effectiveness and safety of posaconazole enteric-coated tablet versus oral suspension in invasive fungal infections.

Posaconazole enteric-coated tablet and oral suspension are two oral drugs in the treatment of invasive fungal infections (IFIs). This study compared the effectiveness and safety between posaconazole enteric-coated tablet and oral suspension, and provided a real world basis for the clinical practice. A retrospective cohort study was performed on IFIs patients treated with posaconazole enteric-coated tablet or oral suspension. The primary endpoints were in-hospital mortality, treatment discontinuation rate and clinical effective rate. The secondary endpoints were adverse events incidence (liver dysfunction, renal dysfunction and hypokalemia). One hundred and forty-four patients were totally included and divided into enteric-coated tablet group (n = 46) and oral suspension group (n = 98). There was no significant difference in effectiveness and safety between two groups. The female (OR = 0.130, P = 0.018) and diabetes mellitus (OR = 4.242, P = 0.003) were independently associated with combined in-hospital mortality/treatment discontinuation rate. The renal replacement therapy (OR = 10.071, P = 0.006), hypoalbuminemia (OR = 6.646, P = 0.002) and posaconazole duration (OR = 1.119, P = 0.002) were risk factors for liver dysfunction. The posaconazole enteric-coated tablet has comparable effectiveness and safety with oral suspension in IFIs, which need large-scale cases studies to confirm in the future.

Invasive Aspergillosis with Cavernous Sinus Thrombosis Following High-Dose Corticosteroid Therapy: A Challenging Case of Rhino-Orbital-Cerebral Mycosis

Invasive aspergillosis is a rare but severe fungal infection primarily affecting immunocompromised individuals. The Coronavirus Disease-2019 (COVID-19) pandemic has introduced new complexities in managing aspergillosis due to the widespread use of corticosteroids for treating COVID-19-related respiratory distress, which can increase susceptibility to fungal infections. Here, we present a challenging case of progressive cerebral aspergillosis complicated by cavernous sinus thrombosis (CST) in a 67-year-old male with a history of COVID-19. The patient, initially misdiagnosed with temporal arteritis, received pulse corticosteroid therapy twice before presenting with persistent left-sided headaches and vision loss. Cranial imaging revealed findings consistent with fungal sinusitis, Tolosa–Hunt syndrome, and orbital pseudotumor, which progressed despite initial antifungal therapy. Subsequent magnetic resonance imaging indicated an invasive mass extending into the left cavernous sinus and other intracranial structures, raising suspicion of aspergillosis. A transsphenoidal biopsy confirmed Aspergillus infection, leading to voriconazole therapy. Despite aggressive treatment, follow-up imaging revealed significant progression, with extension to the right frontal region and left cavernous sinus. The patient then developed visual impairment in the right eye and was diagnosed with CST secondary to fungal sinusitis. Management included a combination of systemic antifungals and antibiotics; however, the patient declined surgical intervention. This case underscores the diagnostic challenges and rapid progression associated with cerebral aspergillosis in post-COVID-19 patients treated with corticosteroids. This report highlights the need for heightened clinical suspicion and prompt, targeted interventions in similar cases to improve patient outcomes. Further research is required to understand the optimal management of invasive fungal infections.

Neutrophil swarming is crucial for limiting oral mucosal infection by Candida albicans.

Oral mucosal colonization by C. albicans (Ca) is benign in healthy people but progresses to deeper infection known as oropharyngeal candidiasis (OPC) that may become disseminated when combined with immunosuppression. Cortisone use and neutropenia are risk factors for invasive mucosal fungal infections, however the mechanisms are poorly understood. Here we identify in vivo neutrophil functional complexes known as swarms that are crucial for preventing Ca epithelial invasion. Anti-Ly6G antibody treatment impaired swarm formation and increased fungal infection depth confirming the role of neutrophil swarms in limiting Ca invasion. Neutrophil swarm function could be disrupted by administration of resolvins, and required leukotriene B4 receptor 1 (BLT1) expression so that administration of a leukotriene synthesis inhibitor reduced neutrophil swarm size permitting Ca invasion beyond the basement membrane. Cortisone treatment similarly reduced neutrophil swarming behavior and BLT1 expression and delayed expression of epithelial cytokines and chemokines. Thus, swarm structures have an important function in preventing deep invasion by C. albicans within the oral mucosa and represent a mechanism for increased disease severity under immune deficient clinical settings.

Fungal Foes: Investigating Novel Approaches For Combating Invasive Fungal Infections In Immunocompromised Patients

Fungal Foes: Investigating Novel Approaches For Combating Invasive Fungal Infections In Immunocompromised Patients

Structure-guided design and synthesis of C22- and C32-modified FK520 analogs with enhanced activity against human pathogenic fungi.

Invasive fungal infections cause significant mortality worldwide, and current antifungal treatments are often ineffective, toxic, or face growing resistance. This research identifies calcineurin (CaN), a critical protein for fungal survival, as a potential target for developing new antifungal drugs. Although existing CaN inhibitors such as FK506 (tacrolimus) and FK520 (ascomycin) possess antifungal properties, their immunosuppressive effects limit their clinical utility. By studying the structure of human and fungal FKBP12-FK506 or FK520 complexes with CaN, we have designed and synthesized modified FK520 derivatives with strong antifungal activity and reduced immunosuppressive effects. These new derivatives are expected to have significantly improved therapeutic profiles, offering hope for more effective and safer antifungal treatments.

Exploring pharmacists’ understanding and use of antifungals at a tertiary hospital in England - an interview study

Abstract Introduction Antimicrobial resistance (AMR) is an emerging crisis worldwide. If continued, it is estimated AMR could cause over 10 million deaths annually by 20501. Antifungals are critical in the treatment and prophylaxis of fungal infections, especially invasive fungal infections which can be life-threatening. The national and international antimicrobial stewardship action plan focus primarily on the use of antibacterials. Antifungals have not yet been a focus for stewardship programmes. The appropriate use and understanding surrounding antifungals remain a challenge among healthcare professionals, including pharmacists but there is scarce empirical evidence to demonstrate this problem. Aim To explore pharmacists’ understanding and use of antifungals at a tertiary hospital in England. Methods A qualitative study utilising a constructivist approach involving one-to-one online semi-structured interview based on the Critical Incident Technique2 was conducted. Pharmacists working in the tertiary hospital were purposively sampled and recruited to participate in the study. Following informed consent, participants took part in a semi-structured interview via Microsoft Teams with a researcher. Interviews explored 1) the general purpose of using antifungals and 2) system factors and decisions taken when managing a routine and unusual or challenging case using antifungals. The interviews were audio-recorded and then transcribed verbatim. Transcripts were analysed using reflexive thematic analysis3. The study was registered with the tertiary hospital where participants were recruited from. This study was registered with Oxford University Hospitals NHS Foundation Trust (ref no. 8482) and received ethical approval from the University of Reading School of Chemistry, Food and Nutritional Sciences and Pharmacy internal ethics review committee (study no: 46/2023). Results Nine participants took part in the study. Interviews took an average of 29 minutes (range 15-55 minutes). Participants worked in different specialties including oncology, haematology, paediatrics, and respiratory care. Three themes were generated through the analysis. Theme 1: Diagnosing and managing fungal infections is complex. Limited and/or lack of reliable and timely diagnostic testing makes diagnosing fungal infections difficult. Consequently, patients were sometimes prescribed empiric antifungals to avoid treatment delay. Treatment was then reviewed once test results were available. Patient-related issues such as comorbidities and drug-drug interactions contribute to complex treatment plans. Theme 2: Antifungal stewardship involved a multidisciplinary approach. Pooling together expertise amongst healthcare professionals was imperative in decision-making. Pharmacists were often key antifungal stewards and medication experts despite working with uncertainty. Theme 3: Expressed need to upskill on antifungal stewardship. Participants were aware of gaps in their experience and knowledge when managing complex fungal infections. They want to be more confident in their role. Discussion/conclusions To our knowledge, this is the first study investigating hospital pharmacists’ understanding and use of antifungals in England. Our study showed that pharmacists navigate uncertainties when using antifungals. Pharmacists were viewed as antifungal stewards and medication experts in a multidisciplinary team but pharmacists were themselves aware that they need more exposure to a wider range of scenarios to enhance their confidence. Our findings suggest a need for reliable diagnostic-driven approaches and education and training initiatives for pharmacists to steward antifungals. Our participants worked in one tertiary hospital representing the culture and work practice specific to the hospital. It would be interesting to explore experiences of pharmacists working in other hospitals.

Rapidly Developing and Elusive Rhino-Orbital-Cerebral Mucormycosis

Purpose: To report a case of rapidly progressing rhino-orbital cerebral mucormycosis that was particularly difficult to diagnose, initially presenting as orbital apex syndrome. Major findings: In this case, a 59-year-old male patient with uncontrolled diabetes presented with a history of facial pain with no ocular involvement. Within 1 day of hospitalization, the patient developed complete ophthalmoplegia and total visual impairment of the right eye. Over the course of 2 hospital stays, several biopsies resulted in no significant histopathological findings, and several cultures resulted in growth of only a single colony of rhizopus mucor from the sinonasal mucosa. Given the high clinical suspicion of an invasive fungal infection, a universal PCR test was performed from a rapidly developing abscess in the frontal lobe and confirmed a diagnosis of mucormycosis. Conclusions: Orbital apex syndrome is a significant diagnosis that can be caused by a variety of factors, including those of fungal, bacterial, neoplastic, or inflammatory origin. Fungal infections, are a particularly concerning cause of orbital apex syndrome, given their ability to penetrate in and through the orbit to the brain, often resulting in an alarmingly high mortality rate. Mucormycosis, specifically rhino-orbital cerebral mucormycosis, is a very severe opportunistic invasive fungal infection, most often afflicting the immunocompromised. A clinician must be very thorough in their workup so as to not miss such a devastating diagnosis. Histopathology and cell cultures are currently the gold standard for diagnosis, with the potential to augment their technical success through the use of molecular techniques, such as universal PCR.

Two distinct clinical progressions of P67phox-deficient CGD, both commencing with cervical lymphadenitis.

We present two rare cases of p67phox-deficient chronic granulomatous disease (CGD) caused by compound heterozygous mutations in the NCF2 gene. They developed cervical lymphadenitis as the initial manifestation of CGD but had distinct clinical progressions. Patient 1 presented with aspergillous meningitis, an extremely rare manifestation of neurological involvement in CGD, which has not been reported before. Patient 2 presented with non-infectious inflammatory lymphadenitis is also very rare and has not been reported previously. These cases emphasize the importance of considering p67phox-deficient CGD in children with late-onset invasive fungal infections and non-infectious inflammatory lesions. Additionally, we also reviewed previous reports of Chinese patients with P67phox-Deficient CGD. Our objective is to raise awareness about the clinical, diagnostic, and genetic characteristics of P67phox-deficient CGD in China, to reduce misdiagnosis and improve the management and prognosis of the disease.

Evaluation of Crushed Posaconazole Delayed Release Tablets in Lung Transplant Recipients.

Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients. A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed. Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1mg/L for those who were therapeutic and 0.4mg/L for those who were not (p < 0.001). The median cumulative dose was 2000mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33%vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy. Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.

A Case of Massive Haemoptysis due to Aneurysm of Left Pulmonary Artery in Patient of COVID 19 with Invasive Fungal Infection

A Case of Massive Haemoptysis due to Aneurysm of Left Pulmonary Artery in Patient of COVID 19 with Invasive Fungal Infection

Genomic Assessment of Resistance of Invasive Fungal Infections in Immunocompromised Patients

Introduction: Invasive fungal infections (IFIs) are emerging and significantly increased in immunocompromised populations. These infections are the most commonly acquired by inhalation of spores and can be transmitted by percutaneous inoculation in cutaneous and subcutaneous infections. Candida and Aspergillus species remain the most common cause of invasive fungal infections including neutropenia, hematological malignancies, bone marrow transplantation, parenteral nutrition prolonged treatment with corticosteroids, chemotherapy, HIV infection, invasive medical procedures, and the newer immune suppressive agents. Materials and Methods: An observational study was carried out at SRM MCH&amp;RC, Tamil Nadu, India, in January 2020. Invasive fungal infections were identified in conventional methods (KOH, Gram staining, culture, sugar assimilation, sugar fermentation, LPCB). Antifungal susceptibility testing was done as per standard guidelines; the resistant species were subjected to molecular testing to identify the gene. Results: Clinical samples are collected from the various departments (blood, pus, tissues, BAL, pleural fluid, and other body fluids). Out of 110 clinical samples, 16 samples were positive for yeast infections and five were positive for moulds. Eighty-nine samples were negative for fungal infection. Among yeast isolates, Candida tropicalis (37%) was the most common in the study population, followed by C albicans (25%), C krusei (19%), C.glabrata (13%), and C.parapsilosis (6%). Among the filamentous fungi, all the isolates were present in the same prevalence. Some of the Candida spp. were found to be resistant to amphotericin B (2), fluconazole (2), and itraconazole (1). All moulds were found to be sensitive to the tested antifungals by microbroth dilution methods. Among the resistant Candida, spp.ERG11 gene was found to be common. Conclusion: We observed that the early detection of etiological agents by microscopy and culture and prompt initiation of antifungal therapy can aid in the reduction of morbidity and mortality among immunocompromised patients.

Antifungal peptide-loaded alginate microfiber wound dressing evaluated against Candida albicans in vitro and ex vivo

Invasive fungal infections have high mortality rates, and many current antimycotics are limited by host toxicity and drug resistance. Recent experiments in our laboratory have demonstrated the antifungal activity of dKn2-7, a synthetic peptide, against Candida albicans. The purpose of the current study was to develop a wound dressing capable of dKn2-7 release for extended periods to help combat fungal infection in wounds. dKn2-7 was incorporated into calcium alginate microfibers, an excipient with known wound healing and hemostatic properties. dKn2-7 release rates from the fibers were dependent on drug loading, but all formulations exhibited a burst release with 41–71 % of total release in the first 15 min and 84–96 % release by 24 h. Calcium release at 15 min was similar to that of a commercial hemostatic dressing, indicating dKn2-7 loading would not adversely affect the hemostatic capability of the alginate fibers. In vitro antifungal studies indicated a dose dependent effect with fibers loaded at ≥20 µg/mg causing significant planktonic killing and ≥30 µg/mg causing significant biofilm killing. Viable fungal counts in biofilms grown on ex vivo porcine skin declined by 99 % following 500 µg/mg fiber treatment. Skin histology indicated no significant differences in tissue damage between treatment groups and controls. Results confirm calcium alginate microfibers are capable of binding and subsequently releasing dKn2-7 over a 24-h period when rehydrated. Furthermore, dKn2-7 released from the fibers was able to significantly reduce biofilms in an ex vivo model with minimal toxicity, indicating these dKn2-7 loaded fiber dressings may be effective at controlling C. albicans biofilm infections in vivo.

Optimizing treatment outcomes in acute-on-chronic liver failure: the role of T2candida panel in detecting invasive candidiasis

IntroductionAcute-on-Chronic Liver Failure(ACLF) is a syndrome characterized by organ dysfunction and high mortality in cirrhotic patients. ACLF has multiple triggers but those precipitated by fungal infection have higher mortality. Early detection and treatment of candidemia have shown mortality benefits in ACLF. The sensitivity of blood cultures ranged from 21% - 71%. Given the increase in mortality, it is vital to have a quick yet reliable diagnostic test for the detection of candida. This study examines the risk of developing ACLF and its impact on survival in hospitalized cirrhotic patients with invasive fungal infection via a positive T2Candida Panel. We also examine the effects of earlier treatment on mortality in those with a positive T2Candida Panel. MethodsWe performed a retrospective study and included cirrhotic patients admitted from 2017-2021. Data collected includes baseline characteristics, labs, progression to ACLF, and mortality outcomes. The stages of ACLF were determined through the use of the CLIF-Consortium ACLF score. ResultsOf the 489 patients sampled, 95 patients developed ACLF during the time of the T2 panel collection, of which 60 (63.2%) (p≤0.001) patients had a positive T2Candida Panel. The data also demonstrates that patients who had earlier antifungal initiation had a decrease in mortality (6.15 ± 5.23 versus 13.53 ± 11.42)(p≤001). ConclusionOur study shows that a positive T2 Panel leads to more frequent progression of ACLF and worsening survival outcomes. This study shows that earlier treatment of candidiasis via the T2 Panel leads to mortality benefits.

Omidubicel for Hematopoietic Cell Transplants: Considerations for Patients and Treatment Outcomes.

For patients with hematologic malignancies requiring allogeneic stem cell transplantation, alternative donor sources are needed when lacking access to a matched related or unrelated donor. Umbilical cord blood (UCB) has been an important alternative allograft donor source for these patients; however, several limitations exist. Omidubicel is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy derived from UCB. Omidubicel was approved in May 2023 by the United States Food and Drug Administration based on the results of a Phase III trial comparing it to UCB transplantation in patients with high-risk hematologic malignancies. Median time to neutrophil engraftment was faster with omidubicel compared to UCB transplantation (12 days vs 22 days; p<0.001). There was also a lower incidence of grade 2/3 bacterial or invasive fungal infections with omidubicel compared to UCB transplantation (37% vs 57%; p=0.027). From a safety perspective, omidubicel has a boxed warning due to the risk of life-threatening infusion reactions, graft-versus-host disease, graft failure, and engraftment syndrome. Omidubicel represents an important advancement in developing novel alternative allograft donor sources. This also has important implications in ensuring access to alternative donor sources for ethnic and minority populations.

SIADH secondary to rhino-orbito-cerebral mucormycosis: A case report.

Invasive fungal mucormycosis and its outcome as SIADH and orbital apex syndrome is uncommon. Mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Early diagnosis and prompt treatment with antifungal, endoscopic surgery, and controlling of diabetes can be beneficial. Mucormycosis is an opportunistic invasive fungal infection which is rare and fatal and can even cause intracranial invasion leading to SIADH. The infrequency with which mucormycosis with SIADH is encountered makes it a formidable diagnostic challenge. 70-year-old women uncontrolled diabetes mellitus presented with bilious vomiting and persistent headache with ptosis, proptosis, absence of extraocular movement, pupillary light reflex, and light perception of left eye. Radiographic investigation, KOH mount, and Biopsy showed mucormycosis in sinus with intracranial extension leading to SIADH. Further investigation revealed hyponatremia, decreased plasma osmolality. Then, when diabetes was controlled and hydrocortisone and amphotericin was given along with Endoscopic sinus debridement, SIADH was well controlled. This case illustrates the potential of mucormycosis in paranasal sinuses can even lead to intracranial invasion and its treatment with the use of amphotericin B can cure improve the prognosis of the disease. Prompt diagnosis through clinical history, radiological investigation, and laboratory parameters are important and its treatment is crucial for the better prognosis.

Yeast-contaminated water as a potential emerging health concern: a review

Invasive fungal infections pose a serious risk to human health; therefore, it is important to study the dissemination and proliferation of pathogenic fungal species in the environment. This could prove useful in preventing infections in susceptible individuals, such as those who are immune-compromised or suppressed. Pathogenic yeasts belonging to the genera Candida, Cryptococcus and Rhodotorula are commonly found in various water sources that are used for daily activities and are included in the World Health Organization fungal priority pathogens list, further warranting investigation into the possibility that infections may occur through contact with yeast-contaminated water. In addition, the close association between antifungal pollutants and yeast in water may induce acquired antifungal resistance development, further complicating the effective treatment of these infections. Thus, investigating the presence and antifungal susceptibility of yeast found in water and identifying ways to monitor potential fungal pathogens may prove useful in combating invasive fungal infections. This review deals with the occurrence and infection risks posed by pathogenic yeasts in water as well as the possibility of these yeasts acquiring antifungal resistance due to the simultaneous presence of antifungal compounds from medical and agricultural runoff.

Crushed posaconazole delayed-release tablets for antifungal prophylaxis and treatment in children.

Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively. However, target attainment is challenging with the oral suspension, particularly in children. Here, we describe our experience using crushed delayed-release tablet (DRT) in a paediatric cohort, with a focus on TDM. We undertook a retrospective audit of crushed posaconazole DRT administration via enteral feeding tubes (EFTs) for patients aged ≤18 years over 18 months at The Royal Children's Hospital Melbourne who had at least one trough concentration measured at steady state. Details of patient demographics, posaconazole dosing, monitoring and adverse effects were recorded. Twelve patients with a median age of 9 years (range 2 to 14) received posaconazole DRT via EFT for prophylaxis (n = 8) or treatment (n = 4). All children achieved target concentration, with a median dose of 7 mg/kg/day (range 5 to 11) for prophylaxis and 13 mg/kg/day (range 9 to 20) for treatment. The median time to reach therapeutic levels was 7 days (range 5 to 14) for prophylaxis and 20 days (range 15 to 35) for treatment. One child had blockage of their EFT, which was attributed to posaconazole. No other adverse effects were observed. Crushed posaconazole DRT administered via EFT may be used as a method of attaining therapeutic posaconazole concentrations in children for antifungal prophylaxis and treatment.

Affinity molecular assay for detecting Candida albicans using chitin affinity and RPA-CRISPR/Cas12a

Invasive fungal infections (IFIs) pose a significant threat to immunocompromised individuals, leading to considerable morbidity and mortality. Prompt and accurate diagnosis is essential for effective treatment. Here we develop a rapid molecular diagnostic method that involves three steps: fungal enrichment using affinity-magnetic separation (AMS), genomic DNA extraction with silicon hydroxyl magnetic beads, and detection through a one-pot system. This method, optimized to detect 30 CFU/mL of C. albicans in blood and bronchoalveolar lavage (BAL) samples within 2.5 h, is approximately 100 times more sensitive than microscopy-based staining. Initial validation using clinical samples showed 93.93% sensitivity, 100% specificity, and high predictive values, while simulated tests demonstrated 95% sensitivity and 100% specificity. This cost-effective, highly sensitive technique offers potential for use in resource-limited clinical settings and can be easily adapted to differentiate between fungal species and detect drug resistance.

Label-Free Optical Transmission Tomography for Direct Mycological Examination and Monitoring of Intracellular Dynamics

Live-cell imaging generally requires pretreatment with fluorophores to either monitor cellular functions or the dynamics of intracellular processes and structures. We have recently introduced full-field optical coherence tomography for the label-free live-cell imaging of fungi with potential clinical applications for the diagnosis of invasive fungal mold infections. While both the spatial resolution and technical set up of this technology are more likely designed for the histopathological analysis of tissue biopsies, there is to our knowledge no previous work reporting the use of a light interference-based optical technique for direct mycological examination and monitoring of intracellular processes. We describe the first application of dynamic full-field optical transmission tomography (D-FF-OTT) to achieve both high-resolution and live-cell imaging of fungi. First, D-FF-OTT allowed for the precise examination and identification of several elementary structures within a selection of fungal species commonly known to be responsible for invasive fungal infections such as Candida albicans, Aspergillus fumigatus, or Rhizopus arrhizus. Furthermore, D-FF-OTT revealed the intracellular trafficking of organelles and vesicles related to metabolic processes of living fungi, thus opening new perspectives in fast fungal infection diagnostics.