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Background: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. Methods: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. Results: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. Conclusion: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management. [ABSTRACT FROM AUTHOR]

We analyzed data on pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of a total of eight Pediatric Hematology-Oncology Departments in Greece for 16 years (2007–2022). A total of twelve patients (11 boys, median age: 9.5 years, range: 2–16) were reported suffering from CNS-IFDs. The underlying malignancy was acute lymphoblastic leukemia in 9/12 and acute myeloid leukemia, Ewing sarcoma, and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e., seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n = 2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n = 1 each). Causative pathogens in probable cases were Aspergillus spp. (n = 2) and Candida spp. (n = 1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19–364). Two patients underwent additional surgical treatment. Six patients were admitted to the Intensive Care Unit due to complications. Three patients (25%) died, two due to IFD and one due to an underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival. [ABSTRACT FROM AUTHOR]

Yanyan Jiang,1 Zhengzheng Chen,1 Huoyang Lv,2 Lihua Jiang,1 Zhiyuan Fan3 1Medical Laboratory Center, Tongxiang First People’s Hospital, Jiaxing, Zhejiang, People’s Republic of China; 2Medical Laboratory Center, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Emergency Medicine, Tongxiang First People’s Hospital, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Zhiyuan Fan, Department of Emergency Medicine, Tongxiang First People’s Hospital, Jiaxing, Zhejiang, People’s Republic of China, Email fanzhiyuan19880916@126.comBackground: Magnusiomyces capitatus (M. capitatus) is a dimorphic opportunistic fungus that is a rare yeast and rarely reported in Asia. Owing to the absence of established clinical breakpoints, the treatment of this fungus poses challenges.Case Presentation: We report a rare case of a young, non-immunocompromised man with cerebral palsy, spinal deformity, and pulmonary M. capitatus infection. The patient’s condition improved after treatment with voriconazole and became stable.Conclusion: M. capitatus infection is commonly associated with hematologic tumors and compromised immunity. Reports of M. capitatus infection in patients with non-immunocompromised host are uncommon. Insufficient understanding of these fungi may lead to underdiagnosis of fungal infection and clinical misdiagnosis, potentially resulting in delayed treatment and increased mortality.Keywords: invasive fungal infection, Magnusiomyces capitatus, MALDI-TOF MS, ITS, cerebral palsy, spinal deformity

Abstract Background Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). Methods BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. Discussion The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. Trial registration ISRCTN11633399. Registered 24/06/2022.

Background: Rapid galactomannan tests, such as the sõna Aspergillus GM Lateral Flow Assay (GM‐LFA) and the Aspergillus Galactomannan Ag VIRCLIA® Monotest (GM‐Monotest), which are suitable for the analysis of single samples, have the potential to accelerate diagnosis of invasive aspergillosis (IA). Objectives: To compare the performance of the GM‐Monotest and the GM‐LFA for the diagnosis of IA. Patients/Methods: Two patient cohorts were analysed: adults who had received an allogeneic haematopoietic stem‐cell transplant (alloHSCT‐cohort) and patients with proven/probable IA from a 5‐year period (cross‐sectional IA‐cohort). In the alloHSCT‐cohort, weekly serum samples were tested, whereas in the cross‐sectional IA‐cohort sera and bronchoalveolar lavage fluids were analysed. The diagnostic performance was calculated using two definitions for positivity: (1) a single positive GM result and (2) at least two positive GM results from consecutive samples. IA classification followed EORTC/MSG 2019. Results: The alloHSCT‐cohort included 101 patients. Four had proven/probable IA, 26 possible IA and 71 no IA. The specificity for one positive serum and two consecutively positive sera was 88.7% and 100% (GM‐Monotest) and 85.9% and 98.6% (GM‐LFA). Comparison of ROC curves in the alloHSCT‐cohort showed no significant difference. The cross‐sectional IA‐cohort included 59 patients with proven/probable IA. The sensitivity for one positive sample and two consecutively positive samples was 83.1% and 55.1% (GM‐Monotest) and 86.4% and 71.4% (GM‐LFA). Conclusions: Both assays showed comparable diagnostic performance with a higher sensitivity for the GM‐LFA if two consecutive positive samples were required for positivity. However, due to poor reproducibility, positive GM‐LFA results should always be confirmed. [ABSTRACT FROM AUTHOR]

Dermatophytic pseudomycetoma (DPM) is a rarely reported invasive fungal infection of humans and animals, especially cats. This study aimed to identify dermatophytes, breed associations, and the frequency of extracutaneous (EC) involvement in feline DPM. Electronic records and formalin-fixed paraffin-embedded tissue (FFPET) from 32 suspected DPM cases in 30 cats were retrieved from a diagnostic laboratory between 2018 and 2024. To confirm DPM and molecular identity, DNA was extracted from FFPET for ITS2 sequencing, and immunohistochemistry was performed on PCR-negative cases. All cases were confirmed as DPM. Microsporum canis was the only dermatophyte identified. The sensitivity and specificity of ITS2 sequencing for M. canis identification in FFPET were 22/32 (68.8%) and 21/22 (95.5%), respectively. Exotic (36.7%) and Persian (23.3%) but not British breeds (26.3%) were over-represented compared to feline admissions at an affiliated veterinary hospital (8.5%, p < 0.001; 3%, p < 0.001; 21.6%, p = 0.817, respectively). Five cases (16.7%) had EC lesions; two had intra-abdominal masses; two had oral cavity masses, including one which extended into the cranial vault; and one had superficial cervical lymph node invasion. Exotic and Persian breeds are over-represented for DPM and M. canis is the primary cause. EC lesions of DPM may occur more commonly than previously thought. [ABSTRACT FROM AUTHOR]

BACKGROUND: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Despite a high infection risk, patients with acute lymphoblastic leukemia (ALL) often do not receive antifungal prophylaxis because of significant drug–drug interactions between azole antifungals and vinca alkaloids. Few studies have examined the incidence and risk factors for fungal infections in adults with ALL. OBJECTIVES: The primary objective of this study was to determine the rates of IFIs (probable and proven) in patients receiving chemotherapy for ALL. The secondary objectives included determining the incidence of invasive candidiasis, the incidence of IFIs based on the intensity of chemotherapy, the incidence of IFIs during each chemotherapy phase, the incidence of IFIs based on disease status, and the organisms involved in IFIs. METHODS: This was a single-center, retrospective cohort study of adults and pediatric patients with ALL who received chemotherapy between July 1, 2014, and June 1, 2019. The definition of IFI followed the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group 2008 criteria. The incidence rates were calculated as the number of diagnosed IFIs divided by the number of person-years at risk, which was defined as the time from the patient’s initiation of chemotherapy until the discontinuation of chemotherapy, transplant, death, or the end of follow-up. RESULTS: Of the 88 patients included in the final analysis, 4 patients had an IFI (incidence, 0.021 infections annually; 95% confidence interval, 0.057-0.53). IFIs only occurred in adults, adolescents, and young adults, and all occurred during induction chemotherapy. The organisms that were identified included Candida lusitanae, Candida dubliniensis, Cryptococcus neoformans, Blastoschizomyces capitatus, and invasive Trichophyton spp. The incidence of IFIs was higher in patients with relapsed or refractory disease than in patients with treatment-naïve ALL (12.1 vs 0.11 infections per 10 patient-years overall, respectively). CONCLUSION: The rates of IFIs were low and were similar to a previous study, which supports the current practice of not routinely using antifungal prophylaxis. The rates of IFIs may be lower in pediatric patients, because no IFIs were identified in this cohort. Further large-scale studies are required to verify our results. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal infections (IFI) are associated with significant morbidity and mortality. The objective of this work was to compare the costs per adult patient, associated with intravenous isavuconazole (ISAV) followed by oral ISAV versus the regimen of liposomal amphotericin B followed by posaconazole (L-AMB→POSA) in the treatment of IFI. The comparison was conducted from the perspective of the Spanish National Health System (SNS). Methods: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration, hospitalization, laboratory tests and adverse events costs were evaluated from SNS perspective. Deterministic and probabilistic sensitivity analyzes were performed. Results: Total costs per-patient were €24,715.54 with ISAV versus €29,753.53 with L-AMB→POSA, resulting in cost-savings per patient treated with ISAV of €5,037.99 (−16.9%). Treatment costs of IFI remained lower for ISAV than for L-AMB→POSA across all sensitivity analyses (−7,968.89€ to −326.59€), being treatment duration the most influential parameter. Conclusion: According to the present model, the treatment of IFIs with ISAV would generate savings for the SNS compared to L-AMB→POSA. These savings are attributed to the shorter duration of IV treatment, reduced use of healthcare resources and lower costs associated with managing adverse effects when ISAV was employed. [ABSTRACT FROM AUTHOR]

Background: The global COVID-19 pandemic has resulted in over seven million deaths, and IFI can further complicate the clinical course of COVID-19. Coinfection of COVID-19 and IFI (secondary IFI) pose significant threats not only to healthcare systems but also to patient lives. After the control measures for COVID-19 were lifted in China, we observed a substantial number of ICU patients developing COVID-19-associated IFI. This creates an urgent need for predictive assessment of COVID-19 patients in the ICU environment for early detection of suspected fungal infection cases. Methods: This study is a single-center, retrospective research endeavor. We conducted a case-control study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. The cases consisted of patients who developed any secondary IFI during their ICU stay at Jilin University China-Japan Union Hospital in Changchun, Jilin Province, China, from December 1st, 2022, to August 31st, 2023. The control group consisted of SARS-CoV-2 positive patients without secondary IFI. Descriptive and comparative analyses were performed, and a logistic regression prediction model for secondary IFI in COVID-19 patients was established. Additionally, we observed an increased incidence of COVID-19-associated pulmonary aspergillosis (CAPA) during this pandemic. Therefore, we conducted a univariate subgroup analysis on top of IFI, using non-CAPA patients as the control subgroup. Results: From multivariate analysis, the prediction model identified 6 factors that are significantly associated with IFI, including the use of broad-spectrum antibiotics for more than 2 weeks (aOR=4.14, 95% CI 2.03-8.67), fever (aOR=2.3, 95%CI 1.16-4.55), elevated log IL-6 levels (aOR=1.22, 95% CI 1.04-1.43) and prone position ventilation (aOR=2.38, 95%CI 1.15-4.97) as independent risk factors for COVID-19 secondary IFI. High BMI (BMI = 28 kg/m²) (aOR=0.85, 95% CI 0.75-0.94) and the use of COVID-19 immunoglobulin (aOR=0.45, 95% CI 0.2-0.97) were identified as independent protective factors against COVID-19 secondary IFI. The Receiver Operating Curve (ROC) area under the curve (AUC) of this model was 0.81, indicating good classification. Conclusion: We recommend paying special attention for the occurrence of secondary IFI in COVID-19 patients with low BMI (BMI < 28 kg/m²), elevated log IL-6 levels and fever. Additionally, during the treatment of COVID-19 patients, we emphasize the importance of minimizing the duration of broad-spectrum antibiotic use and highlight the potential of immunoglobulin application in reducing the incidence of IFI. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a life-threatening fungal infection. Studies focusing on CAPA in low- and middle-income countries are limited. Methods This retrospective matched case-control study was conducted at a tertiary care center in South India. Cases of CAPA were classified using the 2020 European Confederation of Medical Mycology/International Society for Human and Animal Mycology consensus criteria. A total of 95 cases were matched 1:1 with COVID-19 patients without CAPA. Matching was done based on age and period of admission. Inverse probability weighting was used to account for imbalances in COVID-19 severity and intensive care unit (ICU) admission. Data on demographics, clinical details, microbiologic and radiologic data, and treatment outcomes were collected. A predictive score for CAPA was developed from baseline risk factors. Results The predictive score identified lymphopenia, European Organisation for Research and Treatment of Cancer risk factors, and broad-spectrum antibiotic use as the main risk factors for CAPA. Positivity for bacterial pathogens in blood or bronchoalveolar lavage samples reduced the risk of CAPA. The predictive model performed well in cross-validation, with an area under the curve value of 82%. CAPA diagnosis significantly increased mortality and shift to ICU. Conclusions The predictive model derived from the current study offers a valuable tool for clinicians, especially in high-endemic low- and middle-income countries, for the early identification and treatment of CAPA. With further validation, this risk score could improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. Method: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed. Result: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively. Conclusion: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high. [ABSTRACT FROM AUTHOR]

From the existing millions of fungal species, only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck (H&N) over a 19-year period (2005 to 2024) at a large academic healthcare system. Among the 413 documented fungal H&N infections, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with the coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures. [ABSTRACT FROM AUTHOR]

Background: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). Methods: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. Discussion: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. Trial registration: ISRCTN11633399. Registered 24/06/2022. [ABSTRACT FROM AUTHOR]

The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67–40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application. [ABSTRACT FROM AUTHOR]

Background An early diagnosis and treatment of invasive fungal disease (IFD) is associated with improved outcome, but the moderate sensitivity of noninvasive diagnostic tests makes this challenging. Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA (mcfDNA) may facilitate a noninvasive diagnosis. Materials In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius (Redwood City, CA) using their Karius Test (KT) on plasma and a "research use only test" on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, polymerase chain reaction, galactomannan, culture) and used to calculate the sensitivity, specificity, and additional diagnostic value of the KT. Results Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis, 7 (7%) a non- Aspergillus IFD, and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0% (95% confidence interval [CI], 31.2–57.7) and 96.6% (95% CI, 88.5%–99.1%). Sensitivity of the KT was higher in non- Aspergillus IFD (Mucorales :2/3, Pneumocystis jirovecii : 3/5). On BAL, the sensitivity was 72.2% (95% CI, 62.1–96.3), and specificity 83.3% (95% CI, 49.1–87.5). Conclusions Sequencing of mcfDNA may facilitate a noninvasive diagnosis of IFD in particular non- Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a "rule-out" test. [ABSTRACT FROM AUTHOR]

Coronavirus disease of 2019 (COVID-19) predisposes patients to invasive fungal infections. Data on clinical characteristics and outcomes of COVID-19 patients with mucormycosis requiring intensive care unit (ICU) care is limited. The aim of the study was to evaluate the risk factors, myriad presentations, investigations at various stages of disease, and management outcomes of ICU hospitalized COVID-19 patients with mucormycosis. A retrospective chart review was conducted of 32 patients with mucormycosis hospitalized from 23 March, 2020 till 23 March, 2022. Demographic data, comorbidities, complications, treatment, and outcomes were analysed. Average age was 58.8 SD14 years with the majority being males (26 out of 32). Average length of hospital stay was 19 SD14 days. Average time from COVID-19 infection to the diagnosis of mucormycosis was 24 SD16 days. The most common comorbidities observed in the patients included diabetes mellitus (26/32), hypertension (23/32), and obesity (14/32). Twenty sever from 32 patients received steroids, 3 patients received Tocilizumab, and 26 received Remdesivir as treatment for COVID-19 infection. Treatment administered included antifungal medications and surgical intervention. In-hospital mortality rate was 41%. Quick diagnosis of COVID-19 associated mucormycosis (CAM) is a challenge in turn influencing its management and survival. [ABSTRACT FROM AUTHOR]

Blastobotrys is a genus of rare yeast that is increasingly recognized as a cause of fungal infections in humans. However, there have been no reports of fungal infections in humans caused by Blastobotrys mokoenaii. We describe a case of invasive fungal infection (IFI) caused by B. mokoenaii in an immunocompromised patient with acute myeloid leukemia (AML). A 46-year-old man with relapsed/refractory AML underwent a second allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) during remission. The patient had prolonged neutropenia and received systemic steroid therapy for graft-versus-host disease before the second allo-PBSCT. Uncommon yeast was isolated from the blood cultures obtained on day 4. We initially suspected that the uncommon yeast was Trichosporon spp. based on its morphology. However, unlike Trichosporon spp., in vitro antifungal susceptibility tests showed that this yeast isolate was resistant to micafungin, caspofungin, voriconazole, itraconazole, and fluconazole. We performed DNA sequencing and identified it as B. mokoenaii. B. mokoenaii was persistently isolated from blood cultures taken during combination therapy with liposomal amphotericin B and voriconazole. The patient died of multiorgan failure on day 24. B. mokoenaii can cause severe IFI in immunocompromised patients; however, it may not be correctly identified by routine clinical microbiology testing in a hospital laboratory and DNA sequencing is useful for diagnosis. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis is associated with significant morbidity and mortality in patients with haematologic malignancies and haematopoietic cell transplant recipients. The prognosis is worse among patients who have failed primary antifungal treatment. We aim to provide guidance on the diagnosis and management of refractory invasive pulmonary aspergillosis. Using PubMed, we performed a review of original articles, meta-analyses, and systematic reviews. We discuss the diagnostic criteria for invasive pulmonary aspergillosis and the evidence on the treatment of primary infection. We outline our diagnostic approach to refractory disease. We propose a treatment algorithm for refractory disease and discuss the role of experimental antifungal agents. For patients with worsening disease while on antifungal therapy, a thorough diagnostic evaluation is required to confirm the diagnosis of aspergillosis and exclude another concomitant infection. Treatment should be individualized. Current options include switching to another triazole, transitioning to a lipid formulation of amphotericin B, or using combination antifungal therapy. [ABSTRACT FROM AUTHOR]

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%–61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16–32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%–33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%–23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%–27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25–0.5 mg/l), 5-flucytosine (MIC range: 0.5–2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06–0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden. [ABSTRACT FROM AUTHOR]

In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%–60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%–80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%–1%), amphotericin B (0%), and flucytosine (0%–4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections. [ABSTRACT FROM AUTHOR]

Recognising the growing global burden of fungal infections, the World Health Organization (WHO) established an advisory group consisting of experts in fungal diseases to develop a Fungal Priority Pathogen List. Pathogens were ranked based on their research and development needs and perceived public health importance using a series of global surveys and pathogen characteristics derived from systematic reviews. This systematic review evaluates the features and global impact of invasive disease caused by Candida glabrata (Nakaseomyces glabrata). PubMed and Web of Science were searched for studies reporting on mortality, morbidity (hospitalization and disability), drug resistance (including isolates from sterile and non-sterile sites, since these reflect the same organisms causing invasive infections), preventability, yearly incidence, diagnostics, treatability, and distribution/emergence in the last 10 years. Candida glabrata (N. glabrata) causes difficult-to-treat invasive infections, particularly in patients with underlying conditions such as immunodeficiency, diabetes, or those who have received broad-spectrum antibiotics or chemotherapy. Beyond standard infection prevention and control measures, no specific preventative measures have been described. We found that infection is associated with high mortality rates and that there is a lack of data on complications and sequelae. Resistance to azoles is common and well described in echinocandins—in both cases, the resistance rates are increasing. Candida glabrata remains mostly susceptible to amphotericin and flucytosine. However, the incidence of the disease is increasing, both at the population level and as a proportion of all invasive yeast infections, and the increases appear related to the use of antifungal agents. [ABSTRACT FROM AUTHOR]

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%–30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients. [ABSTRACT FROM AUTHOR]

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%–44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4–32 mg/l), while resistance to amphotericin B (MIC: 0.125–0.16 mg/l), itraconazole (MICs: 0.004–0.125 mg/l), and voriconazole (MICs: 0.004–0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat. [ABSTRACT FROM AUTHOR]

Infection remains the leading cause of mortality in severe aplastic anemia (SAA) patients, with invasive fungal infections being the great threat. Aspergillus fumigatus accounts for most of the reported fungal infection cases. Here, we present a case of A. flavus infection in a patient with acute very severe aplastic anemia (VSAA) despite persistently negative clinical fungal tests. The patient was admitted to the hospital due to pancytopenia presisting for over a month and intermittent fever for 10 days. Elevated inflammatory indicators and abnormal lung imaging suggested infection, prompting consideration of fungal involvement. Despite negative results from multiple blood, sputum fungal cultures and the serum (1,3)-β-D-glucan/galactomannan tests. Metagenomic next-generation sequencing (mNGS) on multiple blood samples, alongside clinical symptoms, confirmed A. flavus infection. Targeted antifungal treatment with liposomal amphotericin B and voriconazole significantly ameliorated pulmonary symptoms. Additionally, this study reviewed and compared the symptoms, diagnostic approaches, and treatments from prior Aspergillus infections in AA patients. It emphasizes critical role of early mNGS utilization in diagnosing and managing infectious diseases, offering insights for diagnosing and treating fungal infections in VSAA.

Invasive fungal infection is a life-threatening complication of chemotherapy and neutropaenia in the haematology population. Trichoderma species rarely cause human disease but have been reported to cause invasive infection in the immunosuppressed. We present a case of invasive Trichoderma longibrachiatum pulmonary infection with fatal outcome in a neutropaenic patient with acute myeloid leukaemia. 2012 Elsevier Ltd. All rights reserved.

Introduction. Vulvovaginal candidiasis is an extremely common pathology of the female genital organs, leading to a long-term recurrent course and multiple complications. Although currently it is widely known about developing antibiotic resistance of bacterial pathogens, it is necessary to remember about similar phenomenon observed in other groups of infectious agents. In this regard, fungal infection also requires development of new therapeutic techniques and medicinal antifungal drugs, such as ibrexafungerp. Aim: to analyze available publications revealing the mechanism of action, efficacy, antifungal spectrum and results of clinical trials for a new oral antifungal drug ibrexafungerp. Materials and Methods. A search for publications in the electronic databases PubMed, eLibrary and ClinicalTrials.gov, published over the last 25 years was conducted using the following keywords in Russian and English: “candidiasis”, “vulvovaginal candidiasis”, “antifungal drugs”, “ibrexafungerp”, “clinical trials”, “mechanism of action”. Articles were assessed according to PRISMA guidelines. The titles and abstracts of identified publications were independently reviewed to retrieve relevant full text studies. After the selection procedure, 46 articles were included in the review. Results. This review provides information on the creation of the drug ibrexafungerp, its mechanism of action, the activity against a relatively wide range of pathogens, as well as the results from 13 ongoing and completed clinical trials in patients with fungal infection. Conclusion. The analysis of ibrexafungerp-related clinical studies showed its good oral bioavailability, high antifungal efficacy, so that its one-day dosage may further eliminate a need for unnecessarily long hospitalization and complex dosing schedules, thereby increasing adherence to therapy and odds for treatment success.

Abstract Background Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. Methods The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. Results Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28,

Background and Aim: In this era of the coronavirus disease (COVID) pandemic, new health issues appear quickly and cause an outbreak in India. Here, we focus on invasive fungal infections (IFA), namely mucormycosis, aspergillosis, and candidiasis. Hence, in this article, we focus on conventional techniques for early diagnosis of fungus to help clinicians start empirical treatment for the patient and take necessary steps thereby. Materials and Methods: This observational study was conducted for 1 month, from May 2021 to June 2021, on 200 patients admitted to our mucormycosis ward. Samples were first examined microscopically using potassium hydroxide (KOH) wet mounts followed by culture on sabouraud dextrose agar and the gross appearance of the growth was observed. Further identification of species was achieved through the use of lactophenol cotton blue mounts and slide culture technique. Results: Out of 200 patients, 65.5% were male and 34.5% female. We divided these patients into three age groups, i.e., 20–30 years (15%), 40–60 years (54%), and 60–80 years (31%). Seventy-four percent of patients presented with a history of diabetes mellitus, 50% had a history of steroids taken in their past, and 48% had a history of oxygen therapy taken at the time of COVID-19 positivity (52%) samples positive for mucormycosis. Forty-one percent were KOH-positive for Mucorales and 35.5% were culture positive. The most commonly isolated fungus was Rhizopus, followed by Mucor, Lichthemia, Aspergillus spp., and Candida spp. Conclusion: To improve test sensitivity and enable early diagnosis, other serum biomarkers such as galactomannan, beta-D-glucan, cryptococcal antigenemia, and blood quantitative polymerase chain reaction for Aspergillus or Mucorales should be implemented.

Invasive fungal infections (IFIs) are common and life-threatening complications in post-hematopoietic stem cell transplantation (post-HSCT) recipients, Severe IFIs can lead to systemic infection and organ damage, which results in high mortality in HSCT recipients. With the development of the field of fungal infection diagnosis, more and more advanced non-culture diagnostic tools have been developed, such as glip biosensors, metagenomic next-generation sequencing, Magnetic Nanoparticles and Identified Using SERS via AgNPs+ , and artificial intelligence-assisted diagnosis. The advanced diagnostic approaches contribute to the success of HSCT and improve the overall survival of post-HSCT leukemia patients by supporting therapeutical decisions. This review provides an overview of the characteristics of two high-incidence IFIs in post-HSCT recipients and discusses some of the recently developed IFI detection technologies. Additionally, it explores the potential application of cationic conjugated polymer fluorescence resonance energy transfer (CCP-FRET) technology for IFI detection. The aim is to offer insights into selecting appropriate IFI detection methods and gaining an understanding of novel fungal diagnostic approaches in laboratory settings. [ABSTRACT FROM AUTHOR]

Background Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with subtherapeutic concentrations with the newer delayed-release tablet formulation. Methods In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Results Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis, 5 (22.7%) failed to achieve concentrations ≥0.7 µg/mL, and of 76 patients receiving posaconazole for treatment, 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated. Conclusions A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole, particularly for the treatment of invasive fungal infection, could be considered. [ABSTRACT FROM AUTHOR]

Ruxolitinib, a selective inhibitor of Janus kinases, is a standard treatment for intermediate/high-risk myelofibrosis (MF) but is associated with a predisposition to opportunistic infections, especially herpes zoster. However, the incidence and characteristics of invasive fungal infections (IFIs) in these patients remain uncertain. In this report, we present the case of a 59-year-old woman with MF who developed disseminated histoplasmosis after seven months of ruxolitinib use. The patient clinically improved after ten weeks of combined amphotericin B and azole therapy, and ruxolitinib was discontinued. Later, the patient received fedratinib, a relatively JAK2-selective inhibitor, without relapse of histoplasmosis. We also reviewed the literature on published cases of proven IFIs in patients with MF who received ruxolitinib. Including ours, we identified 28 such cases, most commonly due to Cryptococcus species (46%). IFIs were most commonly disseminated (39%), followed by localized lung (21%) infections. Although uncommon, a high index of suspicion for opportunistic IFIs is needed in patients receiving JAK inhibitors. Furthermore, the paucity of data regarding the optimal management of IFIs in patients treated with JAK inhibitors underscore the need for well-designed studies to evaluate the epidemiology, pathobiology, early diagnosis, and multimodal therapy of IFIs in patients with hematological malignancies receiving targeted therapies. [ABSTRACT FROM AUTHOR]

Despite advancements, invasive fungal infections (IFI) still carry high mortality rates, often exceeding 30%. The challenges in diagnosis, coupled with limited effective antifungal options, make managing IFIs complex. Antifungal drugs are essential for IFI management, but their efficacy can be diminished by drug–drug interactions and pharmacokinetic variability. Therapeutic Drug Monitoring (TDM), especially in the context of triazole use, has emerged as a valuable strategy to optimize antifungal therapy. This review provides current evidence regarding the potential benefits of TDM in IFI management. It discusses how TDM can enhance treatment response, safety, and address altered pharmacokinetics in specific patient populations. TDM plays a crucial role in achieving optimal therapeutic outcomes in IFI management, particularly for certain antifungal agents. Preclinical studies consistently show a link between therapeutic drug levels and antifungal efficacy. However, clinical research in mycology faces challenges due to patient heterogeneity and the diversity of fungal infections. TDM's potential advantages in guiding Echinocandin therapy for critically ill patients warrant further investigation. Additionally, for drugs like Posaconazole, assessing whether serum levels or alternative markers like saliva offer the best measure of efficacy is an intriguing question. [ABSTRACT FROM AUTHOR]

Background Invasive fungal infections (IFI) mainly caused by aspergillus species are one of the leading causes of death in patients undergoing immunosuppressive therapy for hematological malignancies. The presence of galactomannan in bronchoalveolar lavage fluid (BAL GM) is an important diagnostic marker. Some of the factors affecting the BAL GM are still unknown. Antifungal treatment administered before or after BAL also affect BAL GM results. Methods To investigate the effect of BAL GM timing on the diagnosis of IFE, 100 patients receiving immunosuppressive therapy with hematological malignancy at the Uludağ University Faculty of Medicine, Hematology Department, and underwent BAL over a 3-year period with the suspicion of IFE as well as 127 BAL procedures of these patients were examined. Results There were 70 patients who started antifungal therapy before BAL and 30 patients who did not. BAL GM was found positive in 33 (47.1%) of the 70 patients who received antifungal therapy compared to 22 (73.3%) of the 30 patients who did not receive antifungal therapy. There was a significant difference between the two groups in terms of BAL GM positivity (p = 0.016). Subsequently, 127 BAL procedures of these 100 patients were evaluated. When the second, third, and subsequent BAL procedures of the same patients were included in the study, BAL GM was positive in 41 (46.6%) of the 88 procedures in patients who received treatment before BAL and in 25 (64.1%) of the 39 procedures in patients who did not receive treatment before BAL. The rate of BAL GM positivity did not differ between groups (p = 0.068). Conclusions The balance between reducing the risk by initiating early antifungal therapy and maximizing the diagnostic value of BAL GM should be evaluated individually for each patient. [ABSTRACT FROM AUTHOR]

Invasive fungal diseases pose a significant threat to non-neutropenic ICU patients, with Candida and Aspergillus infections being the most common. However, diagnosing these infections in the ICU population remains challenging due to overlapping clinical features, poor sensitivity of blood cultures, and invasive sampling requirements. The classical host criteria for defining invasive fungal disease do not fully apply to ICU patients, leading to missed or delayed diagnoses. Recent advancements have improved our understanding of invasive fungal diseases, leading to revised definitions and diagnostic criteria. However, the diagnostic difficulties in ICU patients remain unresolved, highlighting the need for further research and evidence generation. Invasive candidiasis is themost prevalent form of invasive fungal disease in non-neutropenic ICU patients, presenting as candidemia and deep-seated candidiasis. Diagnosis relies on positive blood cultures or histopathology, while non-culture-based techniques such as beta-D-glucan assay and PCR-based tests show promise. Invasive aspergillosis predominantly manifests as invasive pulmonary aspergillosis in ICU patients, often associated with comorbidities and respiratory deterioration in viral pneumonia. Diagnosis remains challenging due to poor sensitivity of blood cultures and difficulties in performing lung biopsies. Various diagnostic criteria have been proposed, including mycological evidence, clinical/radiological factors and expanded list of host factors. Non-culture-based techniques such as galactomannan assay and PCRbased tests can aid in diagnosis. Antifungal management involves tailored therapy based on guidelines and individual patient factors. The complexity of diagnosing and managing invasive fungal diseases in ICU patients underscore the importance of ongoing research and the need for updated diagnostic criteria and treatment approaches. Invasive fungal disease, Invasive fungal infection, Invasive candidiasis, Invasive aspergillosis, Antifungal drugs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy and safety of isavuconazole (ISA) in the treatment of invasive fungal infection ( IFI), so as to provide evidence-based basis for the selection of clinical treatment strategies. METHODS: Embase, PubMed, Web of Science, the Cochrane Library, VIP, CNKI, Wanfang Data and SinoMed were retrieved to collect the randomized controlled trial (RCT), cohort studies and case-control studies of ISA in the treatment of IFI (the observation group was treated with ISA alone, while the control group received voriconazole or amphotericin B alone) up to May 2023. Quality evaluation and data extraction were performed for the included literature, and Meta-analysis was performed by using RevMan 5. 4. 1 software. RESULTS: A total of 3 RCT, 3 cohort studies and 1 case-control studies were enrolled, including 914 patients. Meta-analysis showed that there were no significant differences in the total effective rate (RR = 1. 00,95%CI = 0. 84-1. 17,P = 0. 96) and all-cause mortality (RR =0. 95,95%CI =0. 76-1. 18,P =0. 62) between the observation group and control group. In terms of safety, the overall incidence of adverse drug reactions in the observation group was lower than that in control group (RR =0. 76, 95%CI =0. 58-0. 99,P =0. 05). The incidences of visual abnormality (RR =0. 47,95%CI =0. 34-0. 67,P<0. 000 1) and liver function injury (RR =0. 56,95%CI =0. 38-0. 83,P =0. 004) in the observation group were significantly lower than those in the control group, the difference was statistically significant. However, there was no statistically significant difference in the incidence of neurological adverse reactions between two groups (RR =1. 04,95%CI =0. 83- 1. 31,P =0. 71). CONCLUSIONS: The efficacy of ISA in the treatment of IFI is similar to that of voriconazole, and the overall safety is better than voriconazole, especially the incidences of liver function injury and visual abnormality are lower than voriconazole. However, it is still necessary to pay attention to the adverse drug reactions of the nervous system during clinical application. [ABSTRACT FROM AUTHOR]

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. [ABSTRACT FROM AUTHOR]

To compare COVID-19-associated pulmonary mucormycosis (CAPM) with COVID-19-associated rhino-orbital mucormycosis (CAROM), ascertain factors associated with CAPM among patients with COVID-19, and identify factors associated with 12-week mortality in CAPM. We performed a retrospective multicentre cohort study. All study participants had COVID-19. We enrolled CAPM, CAROM, and COVID-19 subjects without mucormycosis (controls; age-matched). We collected information on demography, predisposing factors, and details of COVID-19 illness. Univariable analysis was used to compare CAPM and CAROM. We used multivariable logistic regression to evaluate factors associated with CAPM (with hypoxemia during COVID-19 as the primary exposure) and at 12-week mortality. We included 1724 cases (CAPM [n = 122], CAROM [n = 1602]) and 3911 controls. Male sex, renal transplantation, multimorbidity, neutrophil-lymphocyte ratio, intensive care admission, and cumulative glucocorticoid dose for COVID-19 were significantly higher in CAPM than in CAROM. On multivariable analysis, COVID-19-related hypoxemia (aOR, 2.384; 95% CI, 1.209–4.700), male sex, rural residence, diabetes mellitus, serum C-reactive protein, glucocorticoid, and zinc use during COVID-19 were independently associated with CAPM. CAPM reported a higher 12-week mortality than CAROM (56 of the 107 [52.3%] vs. 413 of the 1356 [30.5%]; p = 0.0001). Hypoxemia during COVID-19 (aOR [95% CI], 3.70 [1.34–10.25]) and Aspergillus co-infection (aOR [95% CI], 5.40 [1.23–23.64]) were independently associated with mortality in CAPM, whereas surgery was associated with better survival. CAPM is a distinct entity with a higher mortality than CAROM. Hypoxemia during COVID-19 illness is associated with CAPM. COVID-19 hypoxemia and Aspergillus co-infection were associated with higher mortality in CAPM. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) contribute to morbidity and mortality during acute myeloid leukaemia (AML) treatment. Without prophylaxis, IFI rate during AML treatment in Thailand is high and results in a high mortality rate and a prolonged hospital stay. To evaluate the cost–utility of antifungal therapy (AFT) prophylaxis during AML treatment. We assessed the cost–utility of AFT available in Thailand, including posaconazole (solution), itraconazole (solution and capsule), and voriconazole. A hybrid model consisting of a decision tree and the Markov model was established. The costs to prevent overall IFI using any AFT were all lower than the treatment cost of a non-prophylaxis group, resulting in a saving of 808–1507 USD per patient. Prevention with voriconazole prophylaxis showed the highest quality-adjusted life years (QALYs = 3.51, incremental QALYs = 0.23), followed by posaconazole (QALYs = 3.46, incremental QALY = 0.18) and itraconazole solution (QALYs = 3.45, incremental QALYs = 0.17). Itraconazole capsule reduced QALY in the model. For invasive aspergillosis prevention, posaconazole and voriconazole both resulted in better QALYs and life year savings compared with no prophylaxis. However, posaconazole prophylaxis was the only cost-saving option (976 USD per patient). Posaconazole, itraconazole solution and voriconazole were all cost saving compared with no prophylaxis for overall IFI prophylaxis, with voriconazole being the most cost-effective option. Posaconazole and voriconazole were both cost effective for invasive aspergillosis prevention but only posaconazole was cost saving. A change in reimbursement policy for the use of AFT prophylaxis during intensive AML treatment could provide both clinical benefits to patients and substantial economic benefits to healthcare systems. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objectives: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. Methods: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. Results: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. Conclusion: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Invasive fungal infections (IFIs) are a serious threat to patients with hematological diseases. These infections are characterized by high mortality and lead to significant financial costs for treatment. The most common pathogens of IFIs are Aspergillus spp. and Candida spp., but in recent years, cases of infections caused by rare pathogens have become more frequent. Diagnosis of IFIs and choice of treatment remain challenging due to the nonspecificity of symptoms and the diversity of clinical cases. In this regard, the problem of start time and choice of antifungal therapy remains of current interest. This review briefly describes diagnostic criteria, challenges associated with IFIs diagnosing, provides evidence for empiric and preventive strategies as two early treatment approaches, and examines the impact of therapy initiation on patient outcomes. Treatment of IFIs in hematologic patients should be individualized. At the same time, early administration of therapy with broad-spectrum drugs for febrile neutropenia and parallel diagnostic measures can improve treatment outcomes. There is a lack of current data on the benefits of specific treatment strategies, highlighting the need for further research.

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis.

Introduction. Invasive fungal infection (IFI) is increasingly common in patients at risk, especially those with impaired immune response. In Indonesia, there is currently a low prevalence of IFI which may be influenced by challenges in diagnosis. This study aimed to determine the prevalence and clinical characteristics of IFI patients in Dr. Hasan Sadikin Hospital in Bandung, Indonesia. Methods. This cross-sectional study was conducted at Dr. Hasan Sadikin Hospital. Data were collected using medical records of IFI patients diagnosed between 2020 and 2022 which were selected using total sampling method. Demographic data, clinical symptoms, radiological appearance, and laboratory results were recorded. Results. The prevalence of IFI in Dr. Hasan Sadikin Hospital between 2020 and 2022 was 0,04% (40 per 100,000 patients). The most common cause of invasive fungal infection was Cryptococcus spp. and Candida spp. Fever and loss of consciousness were the two most common signs and symptoms found in this study. HIV/AIDS was present in 51,4% of cases. The diagnostic test was mostly done with cryptococcal antigen (CrAg) examination. Lung involvement was common, appearing as consolidation, infiltration, and ground glass opacity in the lungs. The mortality rate of IFI patients was 51,4%. Conclusions. The prevalence of IFI in Dr. Hasan Sadikin Hospital was quite low, with HIV/AIDS as the most common risk factor. However, there was a high mortality rate found this study is high. Thus, timely diagnosis and antifungal treatment induction should be considered to improve the outcome of invasive fungal infection patients.

We analyzed data on pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of a total of eight Pediatric Hematology-Oncology Departments in Greece for 16 years (2007–2022). A total of twelve patients (11 boys, median age: 9.5 years, range: 2–16) were reported suffering from CNS-IFDs. The underlying malignancy was acute lymphoblastic leukemia in 9/12 and acute myeloid leukemia, Ewing sarcoma, and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e., seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n = 2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n = 1 each). Causative pathogens in probable cases were Aspergillus spp. (n = 2) and Candida spp. (n = 1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19–364). Two patients underwent additional surgical treatment. Six patients were admitted to the Intensive Care Unit due to complications. Three patients (25%) died, two due to IFD and one due to an underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival.

Introduction: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are susceptible to opportunistic infections, including invasive fungal infections (IFI). This is due to many factors, including prolonged immunosuppressive therapy. The treatment of AAV with such IFIs is challenging. Methods: A descriptive analysis of 5 patients with AAV complicated by concomitant invasive fungal infections was performed. We also have done a comprehensive literature review of IFIs in AAV using PubMed and Google Scholar databases. Results: All 5 patients initially received immunosuppressive medication but subsequently acquired IFI. One patient had sphenoid sinus involvement, and four had lung parenchymal involvement. Aspergillus infection was diagnosed in three patients, Cryptococcus infection in one patient and mixed infection with Aspergillus and Mucor infection in one patient. All our patients were on low doses of corticosteroids for several months to years or had received high-dose pulse steroids with cyclophosphamide in the last few weeks before being diagnosed with IFI. It was difficult to distinguish disease activity from IFI in all the cases. Two of the five patients died despite antifungal therapy. The literature review revealed a prevalence of IFIs ranging from 1 to 9.6% (excluding pneumocystis pneumonia). Aspergillosis was the predominant type of IFI, affecting 46 of 86 patients. Most of these patients (40/46) had pulmonary involvement. The prognosis for patients with IFI was consistently poor, as evidenced by 19 deaths out of 29 reported outcomes. Conclusion: Overall, IFIs have a poor prognosis in patients with AAV. Differentiating disease activity from IFI is difficult because of similar organ distribution, imaging lesions, and histopathological characteristics. A high suspicion index and good-quality microbiology are needed for early treatment and prevention of mortality. [ABSTRACT FROM AUTHOR]

Background Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described.- Methods This retrospective, single-center cohort study including 603 lung transplant recipients assessed risk factors for early (within 90 days of transplant) invasive candidiasis (IC) and invasive mold infection (IMI) and late (90–365 days after transplant) IMI using Cox proportional hazard regression. Results In this cohort, 159 (26.4%) patients had 182 IFIs. Growth of yeast on donor culture (hazard ratio [HR], 3.30; 95% CI, 1.89–5.75) and prolonged length of stay (HR, 1.02; 95% CI, 1.01–1.03) were associated with early IC risk, whereas transplantation in 2016 or 2017 (HR, 0.21; 95% CI, 0.06–0.70; HR, 0.25; 95% CI, 0.08–0.80, respectively) and female recipient sex (HR, 0.53; 95% CI, 0.30–0.93) were associated with reduced risk. Antimold therapy (HR, 0.21; 95% CI, 0.06–0.78) was associated with lower early IMI risk, and female donor sex (HR, 0.40; 95% CI, 0.22–0.72) was associated with lower late IMI risk. Recent rejection was a risk factor for late IMI (HR, 1.73; 95% CI, 1.02–2.95), and renal replacement therapy predisposed to early IC, early IMI, and late IMI (HR, 5.67; 95% CI, 3.01–10.67; HR, 7.54; 95% CI, 1.93–29.45; HR, 5.33; 95% CI, 1.46–19.49, respectively). Conclusions In lung transplant recipients receiving universal antifungal prophylaxis, risk factors for early IC, early IMI, and late IMI differ. [ABSTRACT FROM AUTHOR]