Search Results (149)

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

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

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

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

Background: Anti-mold azoles have improved the outcomes of invasive aspergillosis (IA) when used therapeutically, but they are extensively used as prophylaxis. There are limited data regarding the outcomes of patients with hematologic malignancy who develop breakthrough IA on anti-mold azoles. We aimed to determine whether breakthrough IA on azole prophylaxis shows worse outcomes compared to no prophylaxis. Methods: We compared outcomes including therapy response and mortality between antifungal regimens in hematologic malignancy patients with IA between July 1993 and July 2023. Results: Compared to an amphotericin B-containing regimen (AMB), an anti-mold azole as the primary therapy was independently associated with successful response at the end of therapy (OR = 4.38, p < 0.0001), protective against 42-day IA-associated mortality (OR = 0.51, p = 0.024) or all cause mortality (OR = 0.35, p < 0.0001), and protective against 84-day mortality, both IA-associated (OR = 0.50, p = 0.01) and all-cause mortality (OR = 0.27, p < 0.0001). Azole prophylaxis was independently associated with higher IA-associated mortality at 42 days (OR = 1.91, p = 0.012) and 84 days (OR = 2.03, p = 0.004), compared to fluconazole or no prophylaxis. Conclusions: Patients with breakthrough IA on anti-mold azole prophylaxis show a worse prognosis than those on other or no prophylaxis, possibly related to the emergence of azole resistance due to their widespread use as prophylaxis agents. On the other hand, anti-mold azole primary therapy is superior to AMB therapy in the treatment of IA. Full article

Invasive pulmonary aspergillosis (IPA) reports significant mortality rates among critically ill patients. A prompt microbiological diagnosis is essential to establish a coherent antifungal treatment. Despite its low sensitivity and prolonged turn-around time, culture represents the conventional diagnostic technique. Additionally, galactomannan detection may support the diagnostic process. Ultimate generation methods, such as the real-time polymerase chain reaction (Real-Time PCR), integrated the diagnostic procedure to improve the overall laboratory effectiveness, especially regarding a quantitative Aspergillus spp. DNA detection. Herein, we propose a retrospective analysis where a quantitative real-time PCR was performed on respiratory samples belonging to patients with or without probable pulmonary aspergillosis. The study enrolled 62 samples, whose PCR results were compared to culture and galactomannan indexes. Additionally, clinical and general data were collected for all the patients. The qPCR assay reported 100% sensitivity and negative predictive value, while specificity reached 59.2% and the positive predictive value was 76.1%. Moreover, IPA patients reported fungal DNA loads higher than 10³ in a logarithmic scale, while non-aspergillosis episodes reported a maximum level of 10³. We hypothesized a future possibility to define a specific cut-off in distinguishing colonization from infection cases, requiring further investigations and speculations about IPA patients and respiratory samples. Full article

Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with hematological malignancy (HM) and hematopoietic stem cell transplant (HSCT) recipients. Aspergillus terreus is associated with worse outcomes than non-terreus Aspergillus species. Since the introduction of anti-mold azoles in 2002, there have been limited data on the etiology of IA. We retrospectively compared characteristics, antifungal treatments, and outcomes between patients with HM or HSCT infected with A. terreus and those with non-terreus Aspergillus between July 1993 and July 2023. We also examined trends over time in rates of A. terreus and outcomes of this infection. A total of 699 patients with culture-documented IA were analyzed, 537 with non-terreus species and 162 with A. terreus. Types of underlying malignancy, neutropenia, graft-versus-host disease, and anti-mold prophylaxis were similar between the groups. ICU stays and mechanical ventilation were more common among patients with A. terreus (p = 0.002 and 0.003, respectively). The rate of A. terreus decreased significantly from 35.9% during 1993–2003 to 11.2% during 2004–2013 and 16.7% during 2014–2023 (p < 0.0001 each). IA caused by A. terreus showed significant improvements in response to therapy and in overall and IA-associated mortality in the last two decades compared to the first (p < 0.0001). In conclusion, the increased use of anti-mold azoles after 2003 improved outcomes for HM patients with IA caused by A. terreus. Full article

As azole-resistant Aspergillus fumigatus emerges globally, healthcare facilities face mounting challenges in managing invasive aspergillosis. This review synthesizes worldwide azole resistance data to reveal profound regional variability, demonstrating that findings from other regions cannot be directly extrapolated to local settings. Consequently, hospital-level environmental surveillance is crucial for tailoring interventions to local epidemiology and detecting resistant strains in real-time. We outline practical approaches—encompassing sampling site prioritization, diagnostic workflows (culture-based and molecular), and PDCA-driven continuous improvement—so that even resource-limited facilities can manage resistant isolates more effectively. By linking real-time surveillance findings with clinical decisions, hospitals can tailor antifungal stewardship programs and swiftly adjust prophylaxis or treatment regimens. Our approach aims to enable accurate, ongoing evaluations of emerging resistance patterns, ensuring that institutions maintain efficient and adaptive programs. Ultimately, we advocate for sustained, collaborative efforts worldwide, where facilities adapt protocols to local conditions, share data through international networks, and contribute to a global knowledge base on resistance mechanisms. Through consistent application of these recommendations, healthcare systems can better preserve azole efficacy, safeguard immunocompromised populations, and refine infection control practices in the face of evolving challenges. Full article

Aspergillus spp. are ubiquitous fungi present in soil, organic debris, water, decaying vegetation and dust produced in renovation and/or building work. Several studies have shown the presence of aspergilli in various healthcare environments. Typically, thousands of fungal spores are inhaled every day, but if spore clearance fails (typically in immunocompromised patients), fungi can grow and invade lung tissue, causing invasive aspergillosis (IA) which is one of the most frequent infections in highly immunocompromised patients. Aspergillus fumigatus is the most common species involved; this species can be attributed to about 80% of the cases of aspergillosis. According to the WHO, Aspergillus fumigatus is one of four critical priority fungi. The first-line treatment of diseases caused by Aspergillus, in particular IA, is based on triazole antimycotics. Unfortunately, resistance to antimycotics is increasing, partly due to their widespread use in various areas, becoming a significant concern to clinicians who are charged with caring for patients at high risk of invasive mycoses. A recent WHO report emphasised the need for strategies to improve the response, and in particular strengthen laboratory capacity and surveillance, support investment in research and strengthen public health interventions for the prevention and control of fungal infections through a One Health approach. Full article

Invasive aspergillosis (IA) is a fungal infection, which has traditionally been associated with neutropenia and immunosuppressive therapies. Our understanding of invasive aspergillosis has been evolving and, in the past few decades, IA among ICU patients has been recognized as a common infection and has become more widely recognized. The diagnosis and management of invasive aspergillosis in the ICU is particularly challenging, due to the unstable clinical condition of the patients, lack of diagnostic markers, increased risk of further clinical deterioration, multiple comorbidities, and a need for early assessment and treatment. In this article, we will discuss the challenges and pitfalls of the diagnosis and management of invasive aspergillosis in an ICU setting, along with a review of the current literature that is pertinent and specific to this population. Full article

Changes to antifungal therapy (AFT) in invasive aspergillosis (IA) may occur due to intolerance, side effects, drug interactions, or lack of response. We describe AFT change patterns in IA patients. This was a US claims data study. IA patients were identified during the index hospitalization from October 2015 to November 2022. Patients were stratified by whether they ‘changed’ or ‘did not change’ AFT during or after the index hospitalization. AFT patterns were assessed for four lines of therapy or until loss of follow-up. First-line AFT began during the index hospitalization. Discontinuation with restart, modification, or switch in AFT ended the current line and initiated a subsequent line. Inverse probability-of-treatment weighting was utilized. Among 1192 adults with IA, 59.3% changed their AFT (60.0% modified AFT, 22.1% stopped first-line AFT and later initiated a new AFT for second line, and 18% immediately switched to a different AFT). Among those who changed AFT, triazole use predominated, with voriconazole (37.3–49.3%) and isavuconazole (19.3–26.7%) the most used across all AFT lines. Echinocandin use varied between 25.3 and 33.6% over all lines, and amphotericin B use increased over lines 1–4 (13.4–20.7%). Among the 40.7% of patients that completed AFT without changes, most received triazole monotherapy (62.8% voriconazole; 15.2% isavuconazole). Most patients required changes to their AFT. Full article