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11 pages, 400 KiB

Open AccessArticle

The Use of Voriconazole as Primary Prophylaxis for Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation: A Single Center’s Experience

by Ali Atoui, Nadine Omeirat, Omar Fakhreddine, Raquelle El Alam, Zeina Kanafani, Iman Abou Dalle, Ali Bazarbachi, Jean El-Cheikh and Souha S. Kanj

J. Fungi 2021, 7(11), 925; https://doi.org/10.3390/jof7110925 - 31 Oct 2021

Cited by 3 | Viewed by 2892

Abstract

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) [...] Read more.

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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8 pages, 693 KiB

Open AccessArticle

A Reference Laboratory Surveillance on Fungal Isolates from Patients with Haematological Malignancy in Japan

by Yutaro Hino, Akira Watanabe, Rio Seki, Shokichi Tsukamoto, Yusuke Takeda, Emiko Sakaida and Katsuhiko Kamei

J. Fungi 2021, 7(10), 806; https://doi.org/10.3390/jof7100806 - 27 Sep 2021

Viewed by 1682

Abstract

Invasive fungal disease (IFD) in patients with haematological disorders is a fatal disease, making rapid identification and treatment crucial. However, the identification of the causative fungus is often difficult, sometimes even impossible. There have been few reports concerning the causative species of IFD. [...] Read more.

Invasive fungal disease (IFD) in patients with haematological disorders is a fatal disease, making rapid identification and treatment crucial. However, the identification of the causative fungus is often difficult, sometimes even impossible. There have been few reports concerning the causative species of IFD. This study aimed to investigate the epidemiology and causative organism of IFD in patients with haematological diseases in Japan. We analyzed the IFD cases among the patients with haematological malignancies identified at the Medical Mycological Research Center, Chiba University, between 2013 and 2019. The most common underlying disease was acute myeloid leukaemia (34.3%). Forty-six point one percent of IFD patients received haematopoietic stem cell transplantation (HSCT). The major pathogens were Aspergillus, Candida, and Fusarium. Aspergillus fumigatus was the most common Aspergillus species, and Candida fermentati and Fusarium petroliphilum were the most common Candida and Fusarium species, respectively, in this analysis. Furthermore, various cryptic species and non-albicans Candida were identified. The drug susceptibility of such relatively rare strains suggests that analysis of the causative fungi should provide valuable information for therapeutic options. Therefore, our study indicated that it is clinically significant to identify the organism in as much detail as possible. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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11 pages, 4241 KiB

Open AccessArticle

Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach

by Maria Daniela Bergamasco, Carlos Alberto P. Pereira, Celso Arrais-Rodrigues, Diogo B. Ferreira, Otavio Baiocchi, Fabio Kerbauy, Marcio Nucci and Arnaldo Lopes Colombo

J. Fungi 2021, 7(8), 588; https://doi.org/10.3390/jof7080588 - 23 Jul 2021

Cited by 17 | Viewed by 3526

Abstract

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, [...] Read more.

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug–drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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Review

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21 pages, 1458 KiB

Open AccessReview

Invasive Fungal Infections and Targeted Therapies in Hematological Malignancies

by Jessica S. Little, Zoe F. Weiss and Sarah P. Hammond

J. Fungi 2021, 7(12), 1058; https://doi.org/10.3390/jof7121058 - 10 Dec 2021

Cited by 26 | Viewed by 7021

Abstract

The use of targeted biologic therapies for hematological malignancies has greatly expanded in recent years. These agents act upon specific molecular pathways in order to target malignant cells but frequently have broader effects involving both innate and adaptive immunity. Patients with hematological malignancies [...] Read more.

The use of targeted biologic therapies for hematological malignancies has greatly expanded in recent years. These agents act upon specific molecular pathways in order to target malignant cells but frequently have broader effects involving both innate and adaptive immunity. Patients with hematological malignancies have unique risk factors for infection, including immune dysregulation related to their underlying disease and sequelae of prior treatment regimens. Determining the individual risk of infection related to any novel agent is challenging in this setting. Invasive fungal infections (IFIs) represent one of the most morbid infectious complications observed in hematological malignancy. In recent years, growing evidence suggests that certain small molecule inhibitors, such as BTK inhibitors and PI3K inhibitors, may cause an increased risk of IFI in certain patients. It is imperative to better understand the impact that novel targeted therapies might have on the development of IFIs in this high-risk patient population. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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16 pages, 715 KiB

Open AccessReview

Beta-D-Glucan in Patients with Haematological Malignancies

by Malgorzata Mikulska, Elisa Balletto, Elio Castagnola and Alessandra Mularoni

J. Fungi 2021, 7(12), 1046; https://doi.org/10.3390/jof7121046 - 7 Dec 2021

Cited by 11 | Viewed by 6738

Abstract

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report [...] Read more.

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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16 pages, 602 KiB

Open AccessReview

Changing Epidemiology of Invasive Fungal Disease in Allogeneic Hematopoietic Stem Cell Transplantation

by Pedro Puerta-Alcalde and Carolina Garcia-Vidal

J. Fungi 2021, 7(10), 848; https://doi.org/10.3390/jof7100848 - 10 Oct 2021

Cited by 35 | Viewed by 4550

Abstract

Invasive fungal disease (IFD) is a common cause of morbidity and mortality in patients with hematologic malignancies, especially among those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The epidemiology of IFD in HSCT patients has been evolving over the last decades, mainly in [...] Read more.

Invasive fungal disease (IFD) is a common cause of morbidity and mortality in patients with hematologic malignancies, especially among those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The epidemiology of IFD in HSCT patients has been evolving over the last decades, mainly in relation to changes in HSCT therapies such as antifungal prophylaxis. A progressive decrease in Candida albicans infection has been documented, alongside a progressive increase in infections caused by non-albicans Candida species, filamentous fungi, and/or multidrug-resistant fungi. Currently, the most frequent IFD is invasive aspergillosis. In some parts of the world, especially in north Central Europe, a high percentage of Aspergillus fumigatus isolates are azole-resistant. New diagnostic techniques have documented the existence of cryptic Aspergillus species with specific characteristics. An increase in mucormycosis and fusariosis diagnoses, as well as diagnoses of other rare fungi, have also been described. IFD epidemiology is likely to continue changing further due to both an increased use of mold-active antifungals and a lengthened survival of patients with HSCT that may result in hosts with weaker immune systems. Improvements in microbiology laboratories and the widespread use of molecular diagnostic tools will facilitate more precise descriptions of current IFD epidemiology. Additionally, rising resistance to antifungal drugs poses a major threat. In this scenario, knowledge of current epidemiology and accurate IFD diagnoses are mandatory in order to establish correct prophylaxis guidelines and appropriate early treatments. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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17 pages, 335 KiB

Open AccessReview

Invasive Fusariosis in Patients with Hematologic Diseases

by Marcio Nucci, Gloria Barreiros, Tiyomi Akiti, Elias Anaissie and Simone A. Nouér

J. Fungi 2021, 7(10), 815; https://doi.org/10.3390/jof7100815 - 28 Sep 2021

Cited by 30 | Viewed by 3568

Abstract

Fusarium species are filamentous fungi widely encountered in nature, and may cause invasive disease in patients with hematologic conditions. Patients at higher risk are those with acute leukemia receiving induction remission chemotherapy or allogeneic hematopoietic cell transplant recipients. In these hosts, invasive fusariosis [...] Read more.

Fusarium species are filamentous fungi widely encountered in nature, and may cause invasive disease in patients with hematologic conditions. Patients at higher risk are those with acute leukemia receiving induction remission chemotherapy or allogeneic hematopoietic cell transplant recipients. In these hosts, invasive fusariosis presents typically with disseminated disease, fever, metastatic skin lesions, pneumonia, and positive blood cultures. The prognosis is poor and the outcome is largely dependent on the immune status of the host, with virtually a 100% death rate in persistently neutropenic patients, despite monotherapy or combination antifungal therapy. In this paper, we will review the epidemiology, clinical manifestations, diagnosis, and management of invasive fusariosis affecting patients with hematologic diseases. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

18 pages, 663 KiB

Open AccessReview

Cytokine and Chemokine Responses in Invasive Aspergillosis Following Hematopoietic Stem Cell Transplantation: Past Evidence for Future Therapy of Aspergillosis

by Patcharin Thammasit, Jirapas Sripetchwandee, Joshua D. Nosanchuk, Siriporn C. Chattipakorn, Nipon Chattipakorn and Sirida Youngchim

J. Fungi 2021, 7(9), 753; https://doi.org/10.3390/jof7090753 - 13 Sep 2021

Cited by 6 | Viewed by 2818

Abstract

Invasive pulmonary aspergillosis is a frequent complication in immunocompromised individuals, and it continues to be an important cause of mortality in patients undergoing hematopoietic stem cell transplantation. In addition to antifungal therapy used for mycoses, immune-modulatory molecules such as cytokines and chemokines can [...] Read more.

Invasive pulmonary aspergillosis is a frequent complication in immunocompromised individuals, and it continues to be an important cause of mortality in patients undergoing hematopoietic stem cell transplantation. In addition to antifungal therapy used for mycoses, immune-modulatory molecules such as cytokines and chemokines can modify the host immune response and exhibit a promising form of antimicrobial therapeutics to combat invasive fungal diseases. Cytokine and chemokine profiles may also be applied as biomarkers during fungal infections and clinical research has demonstrated different activation patterns of cytokines in invasive mycoses such as aspergillosis. In this review, we summarize different aspects of cytokines that have been described to date and provide possible future directions in research on invasive pulmonary aspergillosis following hematopoietic stem cell transplantation. These findings suggest that cytokines and chemokines may serve as useful biomarkers to improve diagnosis and monitoring of infection. Full article

(This article belongs to the Special Issue Invasive Fungal Diseases in Patients with Hematologic Conditions)

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