Search Results (790)

The genus Aspergillus, widely distributed across natural and urban environments, may cause allergies and opportunistic infections such as chronic or invasive pulmonary aspergillosis. Its high pathogenic potential for immunocompromised patients, together with the alarming increase of azole resistance reported in clinical and environmental isolates, claims urgent actions to assess and control the Aspergillus community in hospital environments. To contribute to that, here, we combine a large environmental survey covering numerous air and surface samples from different zones of three hospitals in Spain, with an integrated approach including general and selective culture- and eDNA-based analyses. Despite the high prevalence of Aspergillus observed, present in almost all indoor zones (mostly in air but also on surfaces) of the three hospitals, its relative abundance in the whole fungal community was limited and dependent on the used methods, with median values ranging from 1.4% (eDNA data) and 6.8% (cultivation at 28 °C) to 28.3% (cultivation at 37 °C). Remarkably, the most protected zones (intensive care units) showed the highest proportion of Aspergillus eDNA sequences. A total of 32 species belonging to 10 Aspergillus sections were molecularly identified, including well-known causal agents of invasive pulmonary infections such as A. fumigatus, A. flavus, A. terreus, A. niger, A. oryzae, A. sydowii, and A. tubingensis. This highlights the importance of such environmental assessments for monitoring and controlling the fungal burden in hospitals. Full article

Mucormycosis is a rare invasive fungal disease in pediatric patients with hematological malignancies and is associated with poor outcomes. We present a fulminant and ultimately fatal case of rhino-orbito-cerebral mucormycosis, addressing important issues including clinical signs and symptoms, diagnostic approaches and the challenges of timely diagnosis. The patient was an 11-year old girl undergoing re-induction chemotherapy for Central Nervous System relapse of B-cell precursor acute lymphoblastic leukemia. She presented six days into the second course of chemotherapy in profound neutropenia with aggravating headaches, painful abducens nerve palsy and anisocoria. At first (day −3), no significant radiological or ophthalmological correlations were found, and methyl–prednisolone was started due to suspected vasculitis following ICU admission. After further clinical deterioration, a second MRI scan (day 0) revealed a prolonged occlusion of the left carotid artery, which was successfully stented in a neuroradiological intervention (day +1). However, during the next day the child developed clinical signs indicating severe cerebral dysfunction. An emergency CT scan showed complete infarction of the left hemisphere including a progredient perfusion deficit and beginning brain edema. Based on the unfavorable prognosis, best supportive care was initiated, and the patient deceased on day +2. Pathological and microbiological workup identified thrombotic infarction in all major cerebral arteries. While microscopy was suspicious for mucormycosis, nested PCR from retained blood specimens confirmed the genus Lichtheimia. Final NGS on brain tissue led to the identification of Lichtheimia ramosa. This case illustrates the rapidity and severity of Mucorales infection. It shows the importance of early clinical suspicion and the need for an aggressive laboratory testing algorithms. The stratification of risk factors and definition of red flags may be a future task fighting these infections. Full article

Candida albicans, listed by WHO as a priority fungal (yeast) pathogen, can cause invasive infections resistant to drugs, thus demanding novel strategies of disinfection. This study examines the inactivation, reactivation in darkness, and susceptibility to fluconazole of an antifungal-resistant C. albicans strain through UVC photolysis, chemical oxidation, and photooxidation using hydrogen peroxide (H₂O₂), peroxydisulfate (PDS), or peroxymonosulfate (PMS). Tests were performed in deionized water over very short treatment times (0–80 s). Also, standardized CLSI methods for antifungal sensitivity studies and morphological microscopic views were carried out. The fungus disinfection order was UVC/H₂O₂ > UVC/PDS > UVC/PMS > UVC. The photooxidation processes followed pseudo-first-order kinetics, with the highest rate constant for the UVC/H₂O₂ process. Direct oxidation, photoinactivation, and attacks of radical species were responsible for the inactivation of the antifungal-resistant microorganism. The fluconazole susceptibility of yeasts was significantly decreased (from 64 to 8 µg mL⁻¹) by the action of UVC/H₂O₂. A low reactivation in the dark and strong changes in the yeast morphology were found, indicating that the use of UVC light and radical-based processes is an effective alternative for fluconazole-resistant yeasts and could be promising to deal with hospital wastewater loaded with resistant fungi. Full article

Invasive fungal infections (IFIs) are one of the most significant public health challenges worldwide. Yet, research and communication thereof were left behind for a long time, until the WHO published a priority pathogens list to guide research, development, and public health action in October 2022. Indeed, due to the rising number of immunocompromised patients at risk and the high level of morbidity, mortality, and economic burden they entail, especially in low- and middle-income countries, IFIs are a serious public health threat. Fungal infections due to dimorphic fungi face additional challenges such as limited knowledge outside of endemic areas and restricted availability of antifungal molecules in areas affected by these infections. The number of related deaths per year is estimated at 2.5 million, but non-governmental organisations make a wider estimation, due to the difficulties in early in vitro diagnostic and troublesome collection and analysis of epidemiological data. Despite this fact, the therapeutic toolbox addressing these infections remains limited, with only four main families of molecules available so far. The antifungal therapeutic supply is composed of very toxic polyenes, the weakly selective and nearly unused 5-fluorocytosine, and azoles, some of which are becoming increasingly inefficient against IFIs. In the 2000–2020s, the fourth arising family consisted of safer semisynthetic echinocandins. Unfortunately, nowadays, more and more fungal isolates encountered in intensive care units exhibit a low susceptibility to echinocandins or are even multiresistant. In this review, we expose the current treatments available to fight against invasive fungal infections. We recall the discovery and physico-chemical aspects of these substances leading to structure/activity and structure/properties relationships. We particularly focus on the to-date resistances and their molecular mechanisms. We finally list some of the most relevant antifungal drug candidates, as they were freshly overviewed by the World Health Organization in April 2025, highlighting the importance of the molecular dimension of this pursuit toward the expansion of the antifungal therapeutic toolbox. Full article

The appressorium is a specialised infection structure formed by Beauveria bassiana during host invasion. This study used sulforaphane to regulate the formation rate of B. bassiana appressoria, evaluated the correlation between appressorium formation and fungal pathogenicity, and explored its impact on insect cuticular metabolism. The results showed that sulforaphane significantly modulated appressorium formation. Spore suspensions with varying appressorium formation rates were injected into Opisina arenosella and Bombyx mori larvae. As the appressorium formation rate increased, B. bassiana exhibited enhanced pathogenicity, leading to accelerated larval mortality. A significant positive correlation (p ≤ 0.05) was observed between appressorium formation and pathogenicity. LC-MS analysis revealed that, prior to appressorium development, larvae activated defence mechanisms involving secondary metabolites, hormone signalling, and toxin metabolism pathways. Following appressorium formation, 61 unique cuticular compounds were identified, along with activation of host lipid metabolism (notably glycerophospholipid degradation), programmed cell death pathways (ferroptosis, necroptosis), and enhanced energy metabolism via the citric acid cycle—collectively indicating disruption of the epidermal defence barrier. Overall, appressorium development by B. bassiana significantly reshapes the metabolic landscape of the larval cuticle, thereby enhancing fungal virulence. This study provides a theoretical foundation for understanding the pathogenic mechanisms of B. bassiana. Full article

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

Tan spot disease, caused by Pyrenophora tritici-repentis, poses a significant threat to wheat production worldwide. Early detection and precise fungicide application are essential for effective disease management. This study explores the potential of Raman spectroscopy—specifically surface-enhanced Raman spectroscopy (SERS) and coherent anti-Stokes Raman scattering (CARS)—as non-invasive tools for identifying fungal infection and assessing wheat’s biochemical response to propiconazole treatment. The methodology is entirely theoretical; no laboratory experiments were conducted. Instead, all spectral graphs and figures were generated through a collaborative process between the author and Microsoft Copilot, which served as a rendering tool. These AI-assisted visualizations simulate Raman responses based on known molecular interactions and literature data. The results demonstrate the conceptual feasibility of Raman-based diagnostics for precision agriculture, offering a sustainable approach to disease monitoring and fungicide management. Full article

Background: Graft-versus-host disease (GVHD) is a rare but serious complication following solid organ transplantation (SOT), particularly in transplants involving organs with a high volume of passenger donor T-lymphocytes. This case highlights the clinical course and diagnostic challenges of GVHD following simultaneous pancreas and pre-emptive kidney transplantation. Methods: A 51-year-old male with long-standing type 1 diabetes mellitus underwent simultaneous pancreas and kidney transplantation with induction therapy using rabbit anti-thymocyte globulin and methylprednisolone. Three months post-transplant, he presented with a diffuse lichenoid cutaneous eruption. Diagnostic evaluation included an extensive infectious workup, skin punch biopsy, liver and bone marrow biopsies, and microchimerism assay. Results: Skin biopsy revealed interface vacuolar dermatitis consistent with cutaneous GVHD. Subsequent liver and bone marrow biopsies confirmed GVHD involvement, with microchimerism assay showing 43% donor-origin T-cells in the bone marrow. Initial treatment with systemic and topical corticosteroids led to temporary improvement. However, the patient developed bone marrow suppression, recurrent bacteremia, and invasive fungal infection, resulting in a prolonged ICU stay and ultimately death. Conclusions: This case underscores the importance of considering SOT-GVHD in patients receiving organs rich in donor lymphocytes, such as pancreas transplants. Early recognition and multidisciplinary management are critical to improving outcomes in this rare but life-threatening condition. Full article

Purpose: Mucormycosis is a life-threatening fungal infection, where rapid diagnosis is critical. We developed a deep learning approach using paranasal computed tomography (CT) images to test whether mucormycosis can be detected automatically, potentially aiding or expediting the diagnostic process that traditionally relies on biopsy. Methods: In this retrospective study, 794 CT images (from patients with mucormycosis, nasal polyps, or normal findings) were analyzed. Images were resized and augmented for training. Two transfer learning models (ResNet50 and ConvNeXt Small) were fine-tuned to classify images into the three categories. We employed a 70/30 train-test split (with five-fold cross-validation) and evaluated performance using accuracy, precision, recall, F1-score, and confusion matrices. Results: The ConvNeXt Small model achieved 100% accuracy on the test set (precision/recall/F1-score = 1.00 for all classes), while ResNet50 achieved 99.16% accuracy (precision ≈0.99, recall ≈0.99). Cross-validation yielded consistent results (ConvNeXt accuracy ~99% across folds), indicating no overfitting. An ablation study confirmed the benefit of transfer learning, as training ConvNeXt from scratch led to lower accuracy (~85%) Conclusions: Our findings demonstrate that deep learning models can accurately and non-invasively detect mucormycosis from CT scans, potentially flagging suspected cases for prompt treatment. These models could serve as rapid screening tools to complement standard diagnostic methods (histopathology), although we emphasize that they are adjuncts and not replacements for biopsy. Future work should validate these models on external datasets and investigate their integration into clinical workflows for earlier intervention in mucormycosis. Full article

Invasive yeast infections (IYIs) remain a significant cause of morbidity and mortality in patients with hematologic diseases. We retrospectively analyzed 193 IYI episodes among 179 patients admitted to a tertiary hematology hospital (2012–2023). Candida species accounted for 91.7% (n = 177), while non-Candida yeasts comprised 8.3% (n = 16). Among invasive candidiasis, non-albicans Candida spp. were predominant, representing 76.8% (136/177), with C. tropicalis (36.2%, 64/177) being the most frequently isolated species. Among non-Candida yeasts, Cryptococcus neoformans (n = 10) was the most commonly identified pathogen. The incidence and 42-day mortality rate of IYIs were 0.199 and 0.095 per 1000 patient-days, respectively. The 42-day case-fatality rate remained high at 47.7%. In categorical analysis, age >65 years, corticosteroid use, elevated lactate (>2 mmol/L), neutropenia (<500/mm³), vasopressor use, and mechanical ventilation were more common in non-survivors. Primary bloodstream infections were more frequent in non-survivors, whereas catheter-related and abdominal-origin infections were predominant among survivors. Concomitant bacteremia was observed in 32.6% of IYI cases (n = 63), with Enterococcus faecium being the most frequently isolated co-pathogen. Our findings illustrate the evolving epidemiology of IYIs in hematologic patients, marked by the emergence of C. tropicalis as the predominant species, sustained mortality, and frequent bacterial co-infections, collectively reflecting the substantial clinical burden of IYIs. Full article

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden—costing billions in healthcare expenditures—fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of “One Health” strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy. Full article

Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021–31 March 2025. Desired isavuconazole exposure was defined as trough concentrations (C_min) of 1.0–5.1 mg/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole C_min underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole C_min was 3.5 mg/L (2.1–4.6 mg/L). Proportions of ECPAs with isavuconazole C_min under- and overexposure were 4.2% (7/166) and 16.3% (27/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg/m²; p < 0.001). Trends of isavuconazole C_min under- and overexposure changed over time, significantly decreasing the former (10.5% <7 days vs. 4.3% 7–28 days vs. 0.0% >28 days; p < 0.001) and increasing the latter (5.3% <7 days vs. 12.8% 7–28 days vs. 29.3% >28 days; p < 0.001). HTD occurred in 15/32 patients, most of whom (10/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment. Full article