Search Results (781)

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

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

Introduction: Acute Myeloid Leukemia (AML) is a hematologic malignancy characterized by the clonal expansion of myeloid progenitors. While it primarily affects the bone marrow, extramedullary relapse occurs in 3–5% of cases, and it is linked to poor prognosis. Central nervous system (CNS) involvement presents diagnostic challenges due to nonspecific symptoms. CNS manifestations include leptomeningeal dissemination, nerve infiltration, parenchymal lesions, and myeloid sarcoma, occurring at any disease stage and frequently asymptomatic. Methods: A 62-year-old man with a recent history of AML in remission presented with diplopia and aching paresthesias in the left periorbital region spreading to the left frontal area. The diagnostic workup included neurological and hematological evaluation, lumbar puncture, brain CT, brain magnetic resonance imaging (MRI) with contrast, and dermatological evaluation with skin biopsy due to the appearance of nodular skin lesions on the abdomen and thorax. Results: Neurological evaluation showed hypoesthesia in the left mandibular region, consistent with left trigeminal nerve involvement, extending to the periorbital and frontal areas, and impaired adduction of the left eye with divergent strabismus in the primary position due to left oculomotor nerve palsy. Brain MRI showed an equivocal thickening of the left oculomotor nerve without enhancement. Cerebrospinal fluid (CSF) analysis initially showed elevated protein (47 mg/dL) with negative cytology; a repeat lumbar puncture one week later detected leukemic cells. Skin biopsy revealed cutaneous AML localization. A diagnosis of AML relapse with CNS and cutaneous localization was made. Salvage therapy with FLAG-IDA-VEN (fludarabine, cytarabine, idarubicin, venetoclax) and intrathecal methotrexate, cytarabine, and dexamethasone was started. Subsequent lumbar punctures were negative for leukemic cells. Due to high-risk status and extramedullary disease, the patient underwent allogeneic hematopoietic stem cell transplantation. Post-transplant aplasia was complicated by septic shock; the patient succumbed to an invasive fungal infection. Conclusions: This case illustrates the diagnostic complexity and poor prognosis of extramedullary AML relapse involving the CNS. Early recognition of neurological signs, including cranial nerve dysfunction, is crucial for timely diagnosis and management. Although initial investigations were negative, further analyses—including repeated CSF examinations and skin biopsy—led to the identification of leukemic involvement. Although neuroleukemiosis cannot be confirmed without nerve biopsy, the combination of clinical presentation, neuroimaging, and CSF data strongly supports the diagnosis of extramedullary relapse of AML. Multidisciplinary evaluation remains essential for detecting extramedullary relapse. Despite treatment achieving CSF clearance, the prognosis remains unfavorable, underscoring the need for vigilant clinical suspicion in hematologic patients presenting with neurological symptoms. Full article

Background/Objectives: The main objective of the study is to assess the clinical utility of microbial cell-free DNA (mcfDNA) in neutropenic patients diagnosed with acute myeloid leukemia (AML) undergoing chemotherapy in the outpatient setting. Neutropenia is a common complication in this patient cohort and enhances the risk of fatal opportunistic bacterial and fungal infections. Accurate and timely diagnosis of these infections in outpatient asymptomatic individuals is critical. Methods: Fourteen patients were studied in this prospective observational case series. Traditional blood cultures (BCs) were obtained when clinically indicated and blood samples were collected for plasma mcfDNA metagenomic sequencing up to two times a week at outpatient oncology appointments. Results were compared in identifying potential infectious agents. Results: BCs identified pathogens in only two patients, despite several cases where infection was suspected. In contrast, mcfDNA testing detected pathogens in 11 of the 14 patients, including bacteria, such as Staphylococcus aureus, and invasive fungi, such as Candida and Aspergillus species, and Pneumocystis jirovecii. Conclusions: In the outpatient setting, mcfDNA surveillance offers a more reliable method for detecting pathogens. This approach identified actionable microbiologic results in immunocompromised individuals who did not meet standard clinical criteria for suspicion of infection. Further research is required to confirm the potential of mcfDNA surveillance in an outpatient setting to guide more accurate treatment decisions, reduce extensive clinical investigations, and improve neutropenic patient outcomes. 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

The Argentine ant (Linepithema humile), listed among the world’s 100 worst invasive alien species, is notoriously difficult to control due mainly to its formation of large, expansive supercolonies. Despite the drawbacks of chemical control, biological alternatives have not been previously explored for this species. In this study, we evaluated six native entomopathogenic fungal strains against Argentine ants from four behaviorally distinct supercolonies, identified through aggression assays and collected from both urban and natural sites within the species’ native range. Ants were inoculated with 1 × 10⁸ conidia/mL using three methods: topical application, spray, and immersion. Mortality was recorded over 14 days, and the cause of death was confirmed by fungal outgrowth from cadavers. Among all strains, Beauveria bassiana Li053 consistently induced high mortality across all supercolonies and inoculation methods, with LT₅₀ values between 2 and 5 days and final mortality rates exceeding 80%. Fungal infection was confirmed in 87–92% of cadavers. Dose–response assays revealed that higher conidial concentrations accelerated and increased mortality, with an LC50 estimated at 1 × 10⁶ conidia/mL. These results demonstrate that B. bassiana Li053 is a promising candidate for the biological control of L. humile and merits further evaluation under field conditions. Full article

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021–2025). Patients received either caspofungin or posaconazole as PAP based on the drug–drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies. 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

Candida auris is an emerging multidrug-resistant fungal pathogen with a high affinity for skin colonization and significant potential for nosocomial transmission. This study aimed to develop and evaluate chitosan-based hydrogels loaded with nystatin and propolis as a topical antifungal strategy for skin decolonization of C. auris. The formulations were selected based on our previous results and optimized for cutaneous application. The internal structure of the hydrogels was investigated by polarized light microscopy, confirming the amorphous nature of propolis and the partial dispersion of nystatin. The antifungal activity was assessed against ten fluconazole-resistant C. auris strains. The CS-NYS-PRO1 formulation demonstrated the highest antifungal performance in the agar test, also reducing viable cell counts to undetectable levels within 6 h. Time–kill assays and SEM imaging confirmed the rapid fungicidal effect and revealed severe membrane disruption and cytoplasmic leakage. Molecular docking analyses indicated the strong binding of nystatin to both sterol 14α-demethylase (CYP51) and dihydrofolate reductase (DHFR) from C. auris, suggesting complementary membrane and intracellular mechanisms of action. These findings support the use of such hydrogels as a local, non-invasive, and biocompatible strategy for managing C. auris colonization, with promising implications for clinical use in infection control and the prevention of skin-mediated transmission in healthcare settings. 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