Search Results (357)

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

Aspergillus can cause a spectrum of diseases depending on the immune status and predisposing conditions. Invasive pulmonary aspergillosis (IPA) is classically seen in patients with severe immunocompromise, such as patients with hematologic malignancies, transplant recipients, and chronic corticosteroid use at high doses. Recently, IPA cases in patients without these classic risk factors, including those associated with severe respiratory viral infections, chronic obstructive pulmonary disease, liver failure, and critical illness, are being increasingly recognized. Delayed recognition and missed diagnoses contribute to increased mortality in these patient populations. Maintaining a high index of suspicion and implementation of systematic screening protocols in high-risk patients may help reduce missed or delayed diagnoses and improve patient outcomes. This review describes the pathophysiology, incidence, risk factors, outcomes, and diagnostic and treatment considerations in IPA in patients with emerging risk factors. Full article

Galactomannan (GM) is a polysaccharide secreted by opportunistic pathogenic fungi of the Aspergillus genus. It is prescribed as a diagnostic biomarker of invasive aspergillosis in immunocompromised patients by the guidelines for diagnosis and management of Aspergillus diseases. It has been shown previously that the measurement of soluble horseradish peroxidase (HRP) using surface-enhanced Raman scattering (SERS) of 2,3-diaminophenazine enzymatic reaction product on silver nanoparticles is largely superior in detection limit compared to colorimetric readout. In this study, a highly sensitive SERS-based HRP measurement protocol was applied to enzyme-linked immunosorbent assay (ELISA) for GM quantification in biological fluids. The detection limit for GM was 4.3 pg per sample, which is one and a half orders of magnitude lower compared to colorimetric detection with o-phenylenediamine as a substrate and five times more sensitive than ELISA using 3,3′,5,5′-tetramethylbenzidine. Full article

Background: Invasive fungal infections (IFIs) after liver transplantation (LT) remain a concern. No universal protocol for antifungal prophylaxis in LT exists. Antifungal prophylaxis varies across European centers. Studies suggest risk stratification for prophylaxis. This study assessed IFI frequency and outcomes in adult LT recipients without antifungal prophylaxis and evaluated risk stratification for predicting IFIs. Method: A retrospective analysis of clinical and microbiological data from 244 liver transplant patients focused on IFI within 100 days post-transplantation. Of these, 225 (92%) had right liver transplants from living donors. We assessed two risk stratification models for predicting IFI: one categorizes patients into low- and high-risk groups, and the other divides patients into three categories, with two eligible for prophylaxis and one not. Results: Of 244 patients, 3% (seven individuals) developed invasive fungal infections (IFI), including two aspergillosis and five candidiasis. IFI occurred in 8% of high-risk and 2% of low-risk patients in the first stratification, with no significant difference between groups (p = 0.144). In the second stratification, IFI was found in 4% of the target and 2% of non-target groups, without a significant difference (p = 0.455). Patients with IFI showed higher mean MELD scores of 21.71 ± 2.35 versus 17.04 ± 6.48 in those without IFI (p < 0.05). Conclusions: This study evaluated IFI outcomes without systemic antifungal prophylaxis in LT recipients. Limited antifungal use in a major living liver donor transplantation (LDLT) group, with low MELD scores and immunosuppression protocols, could be feasible. Future multicenter studies can improve understanding and develop prophylaxis algorithms for LT settings. Full article

Invasive aspergillosis (IA) is a life-threatening infection that mainly affects immunocompromised hosts. Cardiac involvement is rare but can be the sole presentation of IA. It is associated with a high mortality rate and mostly occurs in patients with pre-existing cardiac disease. It can also be seen in immunocompetent patients with a structurally normal heart. The reported cases of cardiac involvement are usually due to infectious endocarditis (IE) caused by Aspergillus species (most commonly Aspergillus fumigatus). However, there is limited data on non-valvular cardiac aspergillosis (NVCA). We reviewed 67 cases of NVCA published between 1950–2024 and reported an additional case from our institution involving a 48-year-old female with kyphoscoliosis diagnosed with Aspergillus pericarditis. Full article

Background: Invasive aspergillosis (IA) is a severe fungal infection increasingly affecting elderly patients with chronic respiratory diseases and prolonged corticosteroid use. Methods: We evaluated clinical, biochemical, and fungal biomarkers in 45 patients over 80 years diagnosed with IA and hospitalized in a Spanish Acute Geriatric Unit. Patients received either voriconazole or isavuconazole. Mortality rates and associated risk factors were analyzed. Results: Overall mortality was 35.61%. Significant mortality risk factors included leukocytosis (p = 0.0371), neutrophilia (p = 0.0144), and lymphopenia (p = 0.0274). Deceased patients had longer hospital stays (26.6 vs. 16.8 days; p = 0.00353). Voriconazole treatment was associated with higher 30-day mortality (61.5% vs. 19.2%; p = 0.0001) and a higher incidence of adverse effects (60% vs. 5%; p = 0.0003) compared to isavuconazole. Voriconazole also showed greater pharmacokinetic variability, with 76.9% of cases outside the therapeutic range. Conclusions: Voriconazole may not be optimal for IA treatment in patients over 80 years. Isavuconazole demonstrated a more favorable safety and efficacy profile. Personalized therapeutic strategies and a multidisciplinary approach are essential to improve clinical outcomes and quality of life in this vulnerable population. Full article

Background: Invasive aspergillosis with orbital apex and intracranial involvement is rare and often misdiagnosed due to nonspecific imaging findings. Misinterpretation may lead to inappropriate therapies, such as corticosteroids, which can exacerbate fungal infections. Case Presentation: A 50-year-old immunocompetent woman with diabetes mellitus presented with right ptosis and systemic malaise. Magnetic resonance imaging (MRI) performed three months prior had shown a subtle low-signal lesion in the right orbital apex. The lesion was small and thought to represent a granulomatous process, with minimal systemic inflammation and only mild surrounding changes on imaging. Biopsy was considered too invasive at that stage, and the patient was placed under observation. Over time, her condition progressed, and repeat imaging revealed intracranial extension, including involvement of the cavernous sinus and frontal lobe. Differential diagnoses included granulomatous diseases such as sarcoidosis or tuberculosis, prompting empirical anti-tuberculosis treatment. However, the patient’s condition worsened, and biopsy of the sphenoid sinus revealed septated fungal hyphae consistent with Aspergillus species on Grocott staining. Voriconazole therapy was initiated, resulting in significant clinical and radiological improvement. Discussion: This case highlights the diagnostic challenge of identifying orbital apex aspergillosis with early MRI changes and demonstrates the risk of misdiagnosis as granulomatous disease. Differentiating fungal infections from other inflammatory etiologies based on subtle imaging features is critical, especially when considering immunosuppressive therapy. Conclusion: Clinicians should maintain a high index of suspicion for fungal infections in patients with progressive orbital apex lesions, even in the absence of classic immunosuppression. Early imaging review and biopsy are essential to prevent misdiagnosis and inappropriate treatment. Full article

(1) Background: Invasive aspergillosis is a life-threatening fungal infection, particularly in patients with hematologic malignancies. Isavuconazole, a broad-spectrum triazole, has emerged as a key treatment option, but real-world data in high-risk populations from middle-income countries remain limited. (2) Methods: We conducted a multicenter, retrospective study to evaluate the clinical response rate and tolerability of isavuconazole in patients with hematologic malignancies and probable or proven invasive aspergillosis across four medical centers in Brazil. (3) Results: We enrolled 50 patients aged 18 to 82 years (64% male) with proven or probable invasive aspergillosis, diagnosed in the context of complex hematologic conditions. Among them, 60% had active or refractory malignancies, and 22% had a prior COVID-19 infection. Isavuconazole was used as a first-line therapy in 64% of cases. No patients discontinued treatment due to toxicity. The 6-week overall survival was 60%. Prior COVID-19 infection was associated with a lower survival rate (44% vs. 69% in patients without COVID-19, p = 0.04). (4) Conclusions: This study provides real-world evidence supporting the efficacy and tolerability of isavuconazole in a high-risk population. The findings reinforce its role as a key antifungal therapy, particularly in patients with complex underlying conditions. Full article

Invasive fungal disease (IFD) is a recognised and potentially life-threatening complication of chronic graft-versus-host disease (cGVHD) and its treatment. Invasive aspergillosis (IA), most often due to the species Aspergillus fumigatus, is the leading IFD in this setting. IA can occur during the early weeks following allogeneic haematopoietic stem cell transplantation (HSCT) coinciding with profound neutropenia, but increasingly, cases of IA occur after engraftment, coinciding with the occurrence of cGVHD. Immunomodulatory treatments of cGVHD can impair innate immune responses to inhaled Aspergillus conidia, increasing the risk of developing IA. Here, in a pilot study, we present an analysis of the phenotypic characteristics (phagocytic efficiency, fungal killing, and cytokine release) of circulating monocytes derived from patients with cGVHD compared to healthy volunteers. We found that there was no statistically significant difference in their ability to phagocytose A. fumigatus conidia, and while there was a trend in their reduced ability to kill conidia, this was not significant when compared to the ability of volunteers’ monocytes to do so. Although we could not demonstrate in this small cohort of patients with cGVHD that monocytes may be a factor in the increased susceptibility to IA, further investigation of larger numbers of study subjects is warranted so that in vitro biomarkers may be developed for immune responses to Aspergillus in patients with cGVHD. Full article

The EORTC/MSGERC definition lacks sufficient sensitivity for diagnosing invasive pulmonary aspergillosis (IPA) in patients with autoimmune inflammatory rheumatic diseases (AIIRDs). We hypothesized that the partial fulfillment of the EORTC/MSGERC definition can improve its diagnostic sensitivity. This retrospective observational study included patients with AIIRDs on immunosuppressive therapy who underwent serum galactomannan antigen testing for suspected IPA. Patients who fulfilled the clinical features or mycological evidence as per the EORTC/MSGERC definition were considered as having “potential IPA.” We compared the clinical characteristics of 364 patients who were categorized into 3 groups—potential IPA (n = 29), proven/probable IPA (n = 24), and non-IPA (n = 311; not meeting any definition). The potential and proven/probable IPA groups had significantly lower survival rates than the non-IPA group (p < 0.001). The potential IPA (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 1.1–3.8) and proven/probable IPA (aHR, 2.6; 95% CI, 1.4–4.9) were independent risk factors for mortality. Compared with the EORTC/MSGERC definition, our proposed criteria improved sensitivity based on the diagnosis at the end of observation (50.0%, 100.0%, respectively). The characteristics and mortality rates of patients were similar between the potential and proven/probable IPA groups. Using these criteria for clinical diagnosis may provide high sensitivity. Full article

Aspergillus spp., particularly A. fumigatus, are increasingly reported as emerging pathogens in cetaceans, yet their clinical and ecological relevance remains poorly characterized. This systematic review synthesizes evidence from 34 studies involving 106 animals, identifying respiratory, neurological, and otic infections as the most frequent presentations with potential interspecies tropism. Invasive disease, frequently fatal, was linked to co-infections—especially with morbillivirus—and environmental stressors such as pollution- and climate-related immune suppression. Despite cetaceans’ role as sentinel species, antifungal susceptibility testing and species-level identification were inconsistently performed. Additionally, azole-resistant A. fumigatus strains were isolated from wild porpoises, indicating environmental antifungal exposure and potential public health implications. Aspergillosis remains underdiagnosed in free-ranging populations, particularly in remote or pelagic species. Conservation implications were scarcely addressed, despite evidence suggesting that fungal disease may contribute to morbidity, stranding, and population impact. This review underscores the need for enhanced surveillance, integrative diagnostics, and recognition of fungal pathogens in a One Health framework. The growing intersection of climate change, emerging mycoses, and wildlife conservation positions Aspergillus infections in cetaceans as both a marine mammal health concern and an ecological indicator of broader environmental changes. Full article

Background: Severe aplastic anemia (SAA) is an uncommon life-threatening disorder characterized by hypocellular bone marrow and pancytopenia. It is typically associated with immune-mediated mechanisms, requiring immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Infections, especially invasive fungal infections such as mucormycosis and aspergillosis, constitute principal causes of morbidity and mortality in patients with SAA. Genetic predispositions, including perforin (PRF1) polymorphisms, may further complicate disease outcomes by impairing immune function. Case report: We describe a case of a 36-year-old female patient diagnosed with SAA, for whom IST was considered, due to the unavailability of a matched sibling donor for HSCT. The patient presented with a feverish condition and deep neck space abscesses were revealed by imaging, caused by invasive aspergillosis. To prioritize infection control, IST was postponed and antifungal therapy with abscess drainage was initiated. However, aspergillosis progressed, despite aggressive and prompt treatment, and ultimately resulted in sepsis, multiorgan failure, and death. In addition, mucormycosis was confirmed post-mortem. Two heterozygous PRF1 polymorphisms (c.272C>T and c.900C>T), were identified by genetic testing, which may have contributed to immune dysregulation and fungal dissemination. Conclusions: The complex interplay between managing SAA and addressing invasive fungal infections, which remain a leading cause of mortality in immunocompromised patients, is highlighted in this case. The latter emphasizes the importance of prompt diagnosis and targeted treatment to alleviate infection-related complications while maintaining care continuity for the hematologic disorder. The detection of PRF1 polymorphisms raises questions about their implication in immune regulation and disease trajectory, emphasizing the need for further research in this field. Full article

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA. Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and clinical outcomes. Subgroup analyses were performed to assess the prognostic value of dual-source galactomannan positivity (positive serum and BAL fluid galactomannan levels). Results: Elevated baseline serum galactomannan levels independently predicted treatment non-response (p = 0.039) and 12-week all-cause mortality (p < 0.001). Peak serum and BAL fluid galactomannan levels were strongly associated with poor clinical outcomes (p < 0.01). Compared to single-source galactomannan positivity, dual-source galactomannan positivity was linked to reduced treatment response (22% vs. 43%, p = 0.01) and higher IA-attributable mortality (52% vs. 27%, p = 0.002). Patients with neutropenia had poorer outcomes compared to patients without neutropenia, but neutrophil recovery dramatically improved survival (25% vs. 69% mortality, p < 0.0001). Early galactomannan kinetics and malignancy type had limited prognostic value. Conclusions: Our findings highlight the potential role of galactomannan as a key biomarker for early prognostication for IA. The strong association between galactomannan levels and clinical outcomes suggests its utility in identifying high-risk patients who may benefit from more aggressive management. Further studies are needed to introduce a nuanced and context-specific use of galactomannan into clinical practice and assess its role as a prognostic biomarker. Full article

Objective: The aim of this study was to estimate the incidence and inpatient outcomes of liver failure and cirrhosis (LFC) admissions with invasive aspergillosis (IA) in the United States. Methods: This retrospective cohort study utilized the 2016–2020 National Inpatient Sample (NIS) database to analyze outcomes of IA in LFC admissions. Baseline variables, including demographics, comorbidities, and complications, were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, and liver transplant admissions were excluded. Outcomes were compared between LFC admissions with and without IA. Results: During the study period, 9515 (0.36%) LFC admissions were associated with IA. This cohort experienced significantly higher rates of complications, including acute kidney injury (AKI) (73.36% vs. 42.96%; p < 0.001) and acute respiratory failure (ARF) (65.74% vs. 24.85%; p < 0.001). IA admissions required invasive mechanical ventilation (IMV) more frequently (58.17% vs. 18.78%; p < 0.001). All-cause inpatient mortality was significantly higher in the aspergillosis group (43.40% vs. 15.75%; p < 0.001). IA admissions had longer lengths of stay (LOS), with 38.89% exceeding 21 days compared to 6.20% (p < 0.001), and a mean LOS more than three times longer (22.9 vs. 7.5 days; p < 0.001). The IA group incurred over four times higher hospital charges (USD 459,414.9 vs. USD 104,389.4; p < 0.001) and hospitalization costs (USD 108,030.6 vs. USD 24,272.1; p < 0.001) compared to the LFC without aspergillosis group. Interpretation: LFC admissions with IA experienced poorer outcomes, longer hospital stays, and significantly higher healthcare costs, underscoring the need for targeted interventions in this high-risk, nonclassical population. Full article

Background/Objectives: Invasive pulmonary aspergillosis (IA) is a common infectious disease in patients with hematological diseases. The prevention, early detection, and establishment of treatment strategies for IA are important. The serum galactomannan antigen (GM) mycological test for IA diagnosis, included in the mycology criteria of the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), is widely used because of its high sensitivity and specificity. However, false-positive results are a concern. Methods: We retrospectively analyzed all GM tests performed at our department in the clinical practice setting between April 2003 and January 2012. Results: Of the 330 cases and 2155 samples analyzed, 540 (25%) were positive (≥0.5). Among the underlying diseases, positivity rates were the highest for multiple myeloma (MM), with 61.3%. By type, positivity rates for IgG, IgA, Bence-Jones protein, and IgD were 71.7%, 33.3%, 57.1%, and 34.6%, respectively. Seventeen out of eighteen cases that were GM-positive at MM diagnosis were false positives, according to the 2008 EORTC/MSG criteria. The IgG and GM values were not directly correlated. Of the seventeen false-positive cases identified, two developed IA during anti-myeloma treatments, and GM values did not become negative during the treatment in most cases. Conclusions: Although subclinical IA may be included in a higher GM index, the results may be prone to false positives; particularly in IgG-type MM, the results should thus be interpreted cautiously. Full article