Editorial

3 pages, 189 KiB

Open AccessEditorial

Invasive Fungal Infections in Children with Haematological Malignancies: Diagnostic and Therapeutic Challenges

by Athanasios Tragiannidis, Antonios Kattamis and Timoleon-Achilleas Vyzantiadis

J. Fungi 2021, 7(7), 516; https://doi.org/10.3390/jof7070516 - 28 Jun 2021

Cited by 4 | Viewed by 1751

The incidence of invasive fungal infections (IFIs) has dramatically increased over the last few decades in parallel with the increased number of immunocompromised patients [...] Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

Research

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11 pages, 228 KiB

Open AccessArticle

Diagnostic Capacity for Invasive Fungal Infections in the Greek Paediatric Haematology-Oncology Units: Report from the Infection Working Group of the Hellenic Society of Paediatric Haematology-Oncology

by Anthi-Marina Markantonatou, Athanasios Tragiannidis, Vasiliki Galani, Dimitrios Doganis, Kondilia Antoniadi, Haroula Tsipou, Maria Lambrou, Nikolaos Katzilakis, Anna Paisiou, Maria Palabougiouki, Marina Servitzoglou, Eugenia Papakonstantinou, Ioulia Peristeri, Efthichia Stiakaki, Eleni Kosmidis, Sophia Polychronopoulou, Antonios Kattamis and Timoleon-Achilleas Vyzantiadis

J. Fungi 2021, 7(5), 357; https://doi.org/10.3390/jof7050357 - 01 May 2021

Cited by 3 | Viewed by 2106

Abstract

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data [...] Read more.

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data from all units, concerning culture-based methods and direct microscopy, phenotypic and molecular identification, sensitivity testing, serology and molecular diagnosis, as well as therapeutic drug monitoring. The target was mostly to reveal the level of laboratory coverage for hospitalised paediatric patients, independently of the possibility of performing the tests in the host hospital, or otherwise to refer the specimens elsewhere. In total, the current study demonstrated that the most important facilities and services regarding the IFD diagnostics for paediatric haematology-oncology patients in Greece are available and relatively easily accessible, with a reasonable turnaround time. Acting as an initial registry for further improvements, the audit can serve as a valuable approach to the actual situation and future perspectives. A national clinical mycology network under the auspices of the relevant scientific societies will probably facilitate collaboration between all the departments (clinical and laboratory) involved in invasive fungal infections and provide an easier approach to any necessary test for any hospitalised patient. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

13 pages, 1118 KiB

Open AccessArticle

Disseminated Mucormycosis in Immunocompromised Children: Are New Antifungal Agents Making a Difference? A Multicenter Retrospective Study

by Sarah Elitzur, Salvador Fischer, Nira Arad-Cohen, Assaf Barg, Miriam Ben-Harosh, Dana Danino, Ronit Elhasid, Aharon Gefen, Gil Gilad, Itzhak Levy, Yael Shachor-Meyouhas, Sigal Weinreb, Shai Izraeli and Shlomit Barzilai-Birenboim

J. Fungi 2021, 7(3), 165; https://doi.org/10.3390/jof7030165 - 25 Feb 2021

Cited by 8 | Viewed by 2724

Abstract

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The [...] Read more.

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The aim of this study was to assess the contemporary management strategies and outcomes of disseminated mucormycosis in the pediatric population. Methods: We conducted a retrospective search in six large tertiary medical centers for all cases of disseminated mucormycosis that occurred between 2009–2020 in patients aged 1–20 years. Results: Twelve cases were identified. Underlying conditions included hematological malignancies (n = 10), solid tumor (post-autologous hematopoietic stem cell transplantations; n = 1), and solid organ (liver) transplantation (n = 1). In all cases, amphotericin B formulations were administered as first-line therapy; in eight cases, they were also administered in combination with an echinocandin or triazole. Seven patients underwent surgical debridement procedures. The six-week mortality was 58%. Among the patients diagnosed between 2009–2015, one of the six survived, and of those diagnosed between 2016–2020, four of the six were salvaged. Conclusions: Disseminated mucormycosis is a life-threatening and often fatal disease, and improved diagnostic and therapeutic strategies are needed. Nevertheless, in this population-based study, five patients (42%) were salvaged through combined liposomal amphotericin/triazole treatment and extensive surgical interventions. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

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8 pages, 263 KiB

Open AccessArticle

Candidemia in Children with Malignancies: Report from the Infection Working Group of the Hellenic Society of Pediatric Hematology-Oncology

by Eleni Vasileiou, Anna Paisiou, Charoula Tsipou, Apostolos Pourtsidis, Vasiliki Galani, Nikolaos Katzilakis, Kondilia Antoniadi, Eugenia Papakonstantinou, Elda Ioannidou, Efthichia Stiakaki, Margarita Baka, Antonios Kattamis, Vasiliki Kitra and Athanasios Tragiannidis

J. Fungi 2020, 6(4), 276; https://doi.org/10.3390/jof6040276 - 10 Nov 2020

Cited by 9 | Viewed by 2404

Abstract

Candidemia is an important cause of morbidity and mortality especially in immunocompromised and hospitalized patients. We retrospectively collected data of candidemia cases that occurred in the seven Hematology-Oncology Departments/Units of Greece and the Stem Cell Transplant Unit between 2015 and 2019. In total, [...] Read more.

Candidemia is an important cause of morbidity and mortality especially in immunocompromised and hospitalized patients. We retrospectively collected data of candidemia cases that occurred in the seven Hematology-Oncology Departments/Units of Greece and the Stem Cell Transplant Unit between 2015 and 2019. In total, 19 episodes of candidemia in 19 patients were recorded. The majority of the patients (78.9%) had at least one risk factor for candidemia. The most frequent risk factors associated with candidemia observed in our patients were prolonged duration of hospitalization (30 days, range 1–141), presence of a central venous catheter at diagnosis of candidemia (73.7%) and antibiotics use during the last two weeks (84.2%). Candida parapsilosis was the most common species isolated accounting for 42.1%, followed by C. albicans (26.3%) and C. famata (15.8%). Nearly all of the patients (84.2%) received antifungal monotherapy with liposomal amphotericin B or echinocandins. The central venous catheter was removed in 78.6% of patients and the median time between the first positive blood culture and catheter removal was 3 days (range 1–9). Mortality at 28 days was 26.3%. In conclusion, a predominance of non-albicans species was observed in our study in conformity with the global trend. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

12 pages, 283 KiB

Open AccessArticle

Rare Invasive Yeast Infections in Greek Neonates and Children, a Retrospective 12-Year Study

by Maria Noni, Angeliki Stathi, Aristea Velegraki, Mika Malamati, Alexandra Kalampaliki, Levantia Zachariadou and Athanasios Michos

J. Fungi 2020, 6(4), 194; https://doi.org/10.3390/jof6040194 - 28 Sep 2020

Cited by 17 | Viewed by 2714

Abstract

Although Candida species remain the leading cause of invasive fungal infections (IFI), the list of other isolated fungal pathogens is increasing. The aim of the study was to report cases of IFI caused by rare yeasts in the largest tertiary Greek pediatric hospital. [...] Read more.

Although Candida species remain the leading cause of invasive fungal infections (IFI), the list of other isolated fungal pathogens is increasing. The aim of the study was to report cases of IFI caused by rare yeasts in the largest tertiary Greek pediatric hospital. A retrospective study was performed from 6/2008–6/2020 regarding IFI caused by rare species. Identification of isolates was attained by conventional, molecular, and MALDI TOF MS methods, and susceptibility testing was performed according to the Clinical and Laboratory Standards (CLSI) methodology. During a 12-year period, 14 different rare fungal species in 33 neonates and children with IFI hospitalized in intensive care and oncology units were isolated from blood, central catheters, peritoneal, pleural, or pericardial fluid specimens. It is the first time for IFI caused by Wickerhamomyces anomalus (Candida pelliculosa), Pichia fermentans (Candida lambica), Yarrowia (Candida) lipolytica, Pichia (Hansenula) kluyveri, Rhodotorula mucilaginosa, Wickerhamiella (Candida) pararugosa and Cyberlindnera (Candida) fabianii in Greek neonates and children to be reported. For most of these rare fungal species isolated in the present study, no official antifungal breakpoints have been defined, and there are no guidelines for their treatment. Clinical laboratories should be aware of uncommon and emerging yeast pathogens and be able to detect them with molecular and proteomic methods. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

Review

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29 pages, 449 KiB

Open AccessReview

Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

by Ioannis Kyriakidis, Eleni Vasileiou, Claudia Rossig, Emmanuel Roilides, Andreas H. Groll and Athanasios Tragiannidis

J. Fungi 2021, 7(3), 186; https://doi.org/10.3390/jof7030186 - 05 Mar 2021

Cited by 17 | Viewed by 5642

Abstract

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated [...] Read more.

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, ⁹⁰Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (⁹⁰Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab). The aim of this narrative review is to describe treatment-related invasive fungal diseases (IFDs) of each category of agents. IFDs are very common in patients under blinatumomab, inotuzumab ozogamicin, basiliximab, gemtuzumab ozogamicin, alemtuzumab, and tisagenlecleucel and uncommon in patients treated with moxetumomab pasudotox, brentuximab vedotin, abatacept, ipilimumab, pembrolizumab and avelumab. Although this new era of precision medicine shows promising outcomes of targeted therapies in children with leukemia or lymphoma, the results of this review stress the necessity for ongoing surveillance and suggest the need for antifungal prophylaxis in cases where IFDs are very common complications. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

17 pages, 2042 KiB

Open AccessReview

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

by Marie Luckowitsch, Henriette Rudolph, Konrad Bochennek, Luciana Porto and Thomas Lehrnbecher

J. Fungi 2021, 7(3), 168; https://doi.org/10.3390/jof7030168 - 26 Feb 2021

Cited by 6 | Viewed by 2552

Abstract

The incidence of invasive mold disease (IMD) has significantly increased over the last decades, and IMD of the central nervous system (CNS) is a particularly severe form of this infection. Solid data on the incidence of CNS IMD in the pediatric setting are [...] Read more.

The incidence of invasive mold disease (IMD) has significantly increased over the last decades, and IMD of the central nervous system (CNS) is a particularly severe form of this infection. Solid data on the incidence of CNS IMD in the pediatric setting are lacking, in which Aspergillus spp. is the most prevalent pathogen, followed by mucorales. CNS IMD is difficult to diagnose, and although imaging tools such as magnetic resonance imaging have considerably improved, these techniques are still unspecific. As microscopy and culture have a low sensitivity, non-culture-based assays such as the detection of fungal antigens (e.g., galactomannan or beta-D-glucan) or the detection of fungal nucleic acids by molecular assays need to be validated in children with suspected CNS IMD. New and potent antifungal compounds helped to improve outcome of CNS IMD, but not all agents are approved for children and a pediatric dosage has not been established. Therefore, studies have to rapidly evaluate dosage, safety and efficacy of antifungal compounds in the pediatric setting. This review will summarize the current knowledge on diagnostic tools and on the management of CNS IMD with a focus on pediatric patients. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

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18 pages, 353 KiB

Open AccessReview

Pneumocystis jirovecii Pneumonia in Children with Hematological Malignancies: Diagnosis and Approaches to Management

by Elpis Mantadakis

J. Fungi 2020, 6(4), 331; https://doi.org/10.3390/jof6040331 - 02 Dec 2020

Cited by 16 | Viewed by 4382

Abstract

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that mostly affects children with suppressed cellular immunity. PJP was the most common cause of infectious death in children with acute lymphoblastic leukemia prior to the inclusion of cotrimoxazole prophylaxis as part of the standard [...] Read more.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that mostly affects children with suppressed cellular immunity. PJP was the most common cause of infectious death in children with acute lymphoblastic leukemia prior to the inclusion of cotrimoxazole prophylaxis as part of the standard medical care in the late 1980s. Children with acute leukemia, lymphomas, and those undergoing hematopoietic stem cell transplantation, especially allogeneic transplantation, are also at high risk of PJP. Persistent lymphopenia, graft versus host disease, poor immune reconstitution, and lengthy use of corticosteroids are significant risk factors for PJP. Active infection may be due to reactivation of latent infection or recent acquisition from environmental exposure. Intense hypoxemia and impaired diffusing capacity of the lungs are hallmarks of PJP, while computerized tomography of the lungs is the diagnostic technique of choice. Immunofluorescence testing with monoclonal antibodies followed by fluorescent microscopy and polymerase chain reaction testing of respiratory specimens have emerged as the best diagnostic methods. Measurement of (1-3)-β-D-glucan in the serum has a high negative predictive value in ruling out PJP. Oral cotrimoxazole is effective for prophylaxis, but in intolerant patients, intravenous and aerosolized pentamidine, dapsone, and atovaquone are effective alternatives. Ιntravenous cotrimoxazole is the treatment of choice, but PJP has a high mortality even with appropriate therapy. Full article

(This article belongs to the Special Issue Invasive Fungal Infections in Paediatric Haematology: Accomplishments and Challenges)

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