Fungal infections in haemato-oncology

2017 ◽  
Author(s):  
Philipp Koehler ◽  
Oliver A. Cornely
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Bone Marrow Failure ◽  
Treatment Strategies ◽  
Underlying Disease ◽  
Haematopoietic Stem Cell ◽  
Graft Versus Host ◽  
Patients At Risk ◽  
Work Up

Invasive fungal infections on haemato-oncology wards present a major challenge. Patients at risk for invasive fungal infection usually have a compromised immune system due to bone marrow failure caused by underlying disease, prolonged neutropenia after intensive chemotherapy, or immunosuppression after haematopoietic stem cell transplantation to avoid graft-versus-host disease. Three major entities—invasive candidiasis, invasive aspergillosis, and mucormycosis—account for the majority of fungal infections. Here, we describe specific host and therapeutic factors predisposing to invasive fungal infection in the haemato-oncology setting. Clinical presentation is highly variable and dependent on the underlying pathogen, organ involvement, and site of infection. Diagnosis is mainly based on radiographic imaging combined with microbiological and histopathological work-up. Various prophylaxis and treatment strategies have been developed, and the evidence for these is discussed.

scholarly journals Challenges and opportunities to understanding genetics of fungal diseases: towards a functional genomics approach

2021 ◽  
Author(s):  
Mariolina Bruno ◽  
Vasiliki Matzaraki ◽  
Frank L van de Veerdonk ◽  
Vinod Kumar ◽  
Mihai G. Netea
Keyword(s):  
Infectious Diseases ◽  
Fungal Infections ◽  
Critical Role ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Fungal Diseases ◽  
Human Pathogens ◽  
Challenges And Opportunities ◽  
Patients At Risk ◽  
Immune Related Genes

Infectious diseases are a leading cause of morbidity and mortality worldwide and human pathogens have long been recognized as one of the main sources of evolutionary pressure, resulting in a high variable genetic background in immune-related genes. The study of the genetic contribution to infectious diseases has undergone tremendous advances over the last decades. Here, focusing on genetic predisposition to fungal diseases, we provide an overview of the available approaches for studying human genetic susceptibility to infections, reviewing current methodological and practical limitations. We describe how the classical methods available, such as family-based studies and candidate-gene studies, have contributed to the discovery of crucial susceptibility factors for fungal infections. We will also discuss the contribution of novel unbiased approaches to the field, highlighting their success but also their limitations for the fungal immunology field. Finally, we show how a systems genomics approach can overcome those limitations and can lead to efficient prioritization and identification of genes and pathways with a critical role in susceptibility to fungal diseases. This knowledge will help stratify patients at risk groups and, subsequently, develop early appropriate prophylactic and treatment strategies.

scholarly journals Epidemiology and Clinical Features of Invasive Fungal Infection in a US Health Care Network

2018 ◽  
Vol 5 (8) ◽  
Author(s):  
Brandon J Webb ◽  
Jeffrey P Ferraro ◽  
Susan Rea ◽  
Stephanie Kaufusi ◽  
Bruce E Goodman ◽  
...  
Keyword(s):  
Health Care ◽  
Fungal Infection ◽  
Clinical Features ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Dimorphic Fungi ◽  
European Organization ◽  
Care Network ◽  
Health Care Network ◽  
Intermountain Healthcare

Abstract Background A better understanding of the epidemiology and clinical features of invasive fungal infection (IFI) is integral to improving outcomes. We describe a novel case-finding methodology, reporting incidence, clinical features, and outcomes of IFI in a large US health care network. Methods All available records in the Intermountain Healthcare Enterprise Data Warehouse from 2006 to 2015 were queried for clinical data associated with IFI. The resulting data were overlaid in 124 different combinations to identify high-probability IFI cases. The cohort was manually reviewed, and exclusions were applied. 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 Consensus Group definitions were adapted to categorize IFI in a broad patient population. Linear regression was used to model variation in incidence over time. Results A total of 3374 IFI episodes occurred in 3154 patients. The mean incidence was 27.2 cases/100 000 patients per year, and there was a mean annual increase of 0.24 cases/100 000 patients (P = .21). Candidiasis was the most common (55%). Dimorphic fungi, primarily Coccidioides spp., comprised 25.1% of cases, followed by Aspergillus spp. (8.9%). The median age was 55 years, and pediatric cases accounted for 13%; 26.1% of patients were on immunosuppression, 14.9% had autoimmunity or immunodeficiency, 13.3% had active malignancy, and 5.9% were transplant recipients. Lymphopenia preceded IFI in 22.1% of patients. Hospital admission occurred in 76.2%. The median length of stay was 16 days. All-cause mortality was 17.0% at 42 days and 28.8% at 1 year. Forty-two-day mortality was highest in Aspergillus spp. (27.5%), 20.5% for Candida, and lowest for dimorphic fungi (7.5%). Conclusions In this population, IFI was not uncommon, affected a broad spectrum of patients, and was associated with high crude mortality.

GM-CSF in Stem Cell Transplant (SCT) Recipients: Impact of Graft-Versus Host Disease on Invasive Fungal Infections (IFIs)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4367-4367
Author(s):  
Amar Safdar ◽  
Gilhen Rodriguez ◽  
Georgina Georgescu ◽  
Richard Champlin
Keyword(s):  
Fungal Infections ◽  
Underlying Disease ◽  
P Value ◽  
High Dose ◽  
Cell Transplant ◽  
Retrospective Case ◽  
Graft Versus Host ◽  
Gm Csf ◽  
Younger Age ◽  
The Impact

Abstract Background: GM-CSF is thought to be beneficial in SCT patients with IFI. The impact of GM-CSF in SCT recipients with GVHD and IFI was evaluated Methods: A retrospective case-matched (GM-CSF [n = 12] vs. no GM-CSF [n = 27]) study was undertaken to compare outcomes if IFIs diagnosed >100 days following transplantation during 2000–2006. A response was defined as complete or partial response (CR/PR) and considered 3 months after IFI diagnosis or earlier in patients with earlier response. All value are given as median ± s.d. The systemic antifungal therapy in > 60% of patients included echinocandin and anti-mold triazole, or polyene agent. Results: Please refer to the table below. Patients who received GM-CSF were younger (age 36 ± 17 vs. 51 ± 13 years); neutropenic (<500 cells/uL) at onset of infection (50% vs. 11%; P = 0.014); had lower monocyte counts (10 ± 236 vs. 220 ± 575 cells/uL; P = 0.021) and frequently required intensive care unit stay (50% vs 15%; P = 0.043). A 50% response was observed in the GM-CSF treated SCT recipients with GVHD and IFIs, whereas, 41% response occurred in the group who received no concurrent Gm-CSF (P = 0.6). Similarly, IFI-associated deaths were less frequently observed in GM-CSF treated patients (41%) compared with 55% seen in patients who had not received GM-CSF (P = 0.7). There was a slight increase in survival among SCT recipients treated with GM-CSF (48 ± 21 days vs. 34 ± 19 days in no GM-CSF group P = 0.05) Conclusions: Late fungal infections in SCT recipients with GVHD, when treated with GM-CSF-based therapy had comparable outcomes despite having significantly more neutropenia, severe monocytopenia and ICU stay. Characteristics GM-CSF N = 12 (5% No GM-CSF N = 27 (%) p-value Underlying Disease-Leukemia Relapsed/refractory Cancer 10 (83) 5 (42) 18 (67) 6 (22) 0.12 0.26 Proven and probable IFI 9 (75) 21 (78) 1 GVHD (extensive) 5 (42) 14 (52) 0.57 High Dose Steroids 7 (58) 18 (67) 0.72 Disseminated IFI 3 (25) 4 (15) 0.65 Breakthrough IFI 10 (83) 25 (93) 0.57 APACHI II Score at time of IFI diagnosis 11+/−4 (range 5–18) 12+/−3 (range 5–19) 0.47

scholarly journals Disseminated Geosmithia argillacea Infection in a Patient with Ph-Positive Acute Lymphoblastic Leukemia. Case Report and Literature Review

2021 ◽  
Vol 7 (9) ◽  
pp. 778
Author(s):  
Antonio Giordano ◽  
Francesca Di Landro ◽  
Elena De Carolis ◽  
Marianna Criscuolo ◽  
Giulia Dragonetti ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Clinical Effect ◽  
Lymphoblastic Leukemia ◽  
Major Complication ◽  
Molecular Diagnostic ◽  
Graft Versus Host ◽  
Drug Of Choice ◽  
Clinical Conditions

Invasive fungal infection (IFI) remains the major complication in patients with either acute leukemia, allogeneic stem cell transplantation setting, or both, especially regarding pulmonary localization. We report an experience of a 74-year-old Caucasian male with a Philadelphia-positive (BCR-ABL p190) Common B-acute lymphoblastic leukemia (ALL) who developed a pulmonary infection due to Geosmithia argillacea. Furthermore, we describe the management of this complication and the results of microbiological tests useful to guide the treatment. All cases reported show failure of voriconazole treatment. In the majority of cases a good susceptibility to posaconazole has been reported, which seems to have a good clinical impact; however, only L-AmB shows a clinical effect to produce quick clinical improvement and so it should be a drug of choice. A literature revision shows that only a few papers have thus far described this infection, at present only one case was reported in a hematological setting like a gastrointestinal graft versus host disease in an allogeneic HSCT recipient. The severity of clinical conditions in hematological malignancy settings requires improving the management of this emerging invasive fungal infection. Indeed, a molecular diagnostic approach with a tight laboratory collaboration and targeted therapy should become the gold standard.

scholarly journals 78. Non-Invasive Prediction of Invasive Fungal Infection by Plasma-Based Microbial Cell-Free DNA Next-Generation Sequencing (mcfDNA NGS) in Pediatric Patients with Relapsed or Refractory Leukemia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S51-S51
Author(s):  
Joshua Wolf ◽  
Joshua Wolf ◽  
Gabriela Maron ◽  
Kathryn Goggin ◽  
Kim J Allison ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Pathogen ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Non Invasive ◽  
Clinical Onset ◽  
Fungal Dna

Abstract Background Diagnosis of invasive fungal infections (IFIs), a life-threatening complication of cancer therapy or hematopoietic cell transplantation (HCT) can be challenging, and IFI has poor outcomes. Prediction or early non-invasive diagnosis of IFI in high-risk hosts before onset of symptoms could reduce morbidity and mortality. Because non-invasive plasma mcfDNA NGS can detect invasive fungal infections, and may predict bloodstream infections in immunocompromised patients, we hypothesized that mcfDNA NGS might also predict invasive fungal infection before clinical presentation. Methods In a prospective study, serial remnant plasma samples were collected from pediatric patients undergoing treatment for relapsed or refractory leukemia. IFI events were classified according to EORTC criteria by 2 independent experts, and episodes empirically treated for suspected IFI, but not meeting ‘possible’ criteria were classified as ‘suspected’. All samples collected within 30 days before clinical diagnosis of non-fungemic IFI were tested for fungal DNA by mcfDNA NGS using a research-use only assay by Karius, Inc. optimized for fungi; because of overlapping clinical syndromes, non-fungal DNA was not considered in this study. Results There were 15 episodes of suspected IFI in 14 participants with ≥1 sample available from either diagnostic (within 1 day of diagnosis) or predictive (2 to 30 days prior to diagnosis) periods (5 “suspected”, and 4 probable and 6 proven by EORTC definitions). Of 10 probable or proven IFIs, 6 (60%) had a relevant fungal pathogen identified mcfDNA NGS at diagnosis. In each of these cases the fungal DNA was also detectable prior to clinical onset of IFI (Range 2 to 41 days; Figure 1). In an additional case, manual review of sequence data identified the fungal DNA at diagnosis and during the prior month. Of 5 “suspected” IFI episodes, all were determined by expert review as not representing fungal infection; fungal DNA was identified by mcfDNA NGS in 2/54 (3.7%) of samples from these episodes. Table 1. Characteristics of Invasive Fungal Infections Conclusion mcfDNA NGS can identify fungal pathogen DNA before clinical onset of IFI, so might predict IFI in immunocompromised hosts, and may help differentiate fungal infection from other etiologies of lung nodules or infiltrates. Disclosures Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose Radha Duttagupta, PhD, Karius inc (Employee) Lily Blair, PhD, Karius Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee)

scholarly journals Fungal Infection in Lung Transplantation

2021 ◽  
Vol 42 (03) ◽  
pp. 471-482
Author(s):  
Cassie C. Kennedy ◽  
Kelly M. Pennington ◽  
Elena Beam ◽  
Raymund R. Razonable
Keyword(s):  
Fungal Infection ◽  
Fungal Pathogens ◽  
Lung Transplant ◽  
Fungal Infections ◽  
Treatment Strategies ◽  
Invasive Fungal Infections ◽  
Molecular Diagnostic ◽  
Candida Spp ◽  
Diagnostic Strategies ◽  
Culture Techniques

AbstractInvasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve.

scholarly journals Refractory recurrent ocular graft versus host disease

2019 ◽  
Vol 12 (12) ◽  
pp. e232579 ◽  
Author(s):  
Emily Greenan ◽  
Elisabeth Vandenberghe ◽  
Conor C Murphy
Keyword(s):  
Graft Versus Host Disease ◽  
Treatment Strategies ◽  
Surface Damage ◽  
Haematopoietic Stem Cell ◽  
Ocular Tissue ◽  
Host Disease ◽  
Graft Versus Host ◽  
Tissue Changes

Ocular graft-versus-host disease (GVHD) is one of the most frequent and long-term complications affecting patients after haematopoietic stem cell transplantation. It is associated with significant morbidity and a marked reduction in quality of life. Although common, currently there are no widely accepted guidelines available for its management, and no suggested regime of treatment that is completely satisfactory. So far, prophylactic treatment strategies for ocular GVHD have yet to be developed and treatment is normally initiated based on symptoms often after permanent ocular tissue changes and surface damage has occurred. Here we describe a case of recurrent ocular GVHD and its associated complications that was highly refractory to treatment.

scholarly journals Dosing of Antimycotic Treatment in Sepsis–Induced Liver Dysfunction by Functional Liver Testing with LiMAx®

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Carmen Kirchner ◽  
Jasmin Sibai ◽  
Elke Schwier ◽  
Dietrich Henzler ◽  
Claas Eickmeyer ◽  
...  
Keyword(s):  
Liver Function ◽  
Fungal Infection ◽  
Medical History ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Multiorgan Failure ◽  
Clinical Status ◽  
Good Condition ◽  
Added Value ◽  
Renal Infarction

Background. Sepsis-treatment is one of the major challenges in our time. Especially fungal infections play an important role in patient’s morbidity and mortality. In patients with septic shock, liver function is often significantly impaired and therefore also hepatic drug metabolism is altered. Case Presentation. We report about a 56-year-old man suffering from invasive fungal infection with multiorgan failure, after complicated medical history due to symptomatic infrarenal aortic aneurysm. On the first postoperative day, a CT scan was undertaken due to massive back pain showing renal infarction on both sides. As qualitative and quantitative renal function was impaired, hemodialysis was started immediately. Subsequently, the patient developed a compartment syndrome of the left leg and underwent fasciotomy. On admission day 7, the patient presented with hematochezia leading to colonoscopy. During this procedure, an ischemic colitis was observed. As conservative treatment failed, the patient underwent Hartmann’s procedure due to progredient ischemia followed by a worsening of the clinical status due to sepsis. The patient suffered from an invasive fungal infection with Candida spp. and Aspergillus spp. Systemic antifungal treatment was initiated. Although azoles are considered first-line treatment in these cases we chose the echinocandin caspofungin for its presumed lower impact on liver function compared to azoles like voriconazole or Amphothericin B. However, caspofungin is also metabolised in the liver and can cause hepatotoxic effects. Therefore we measured metabolic liver function capacity using LiMAx®and adapted the patient’s dose of caspofungin to the evaluated liver function capacity to achieve an effective and liver-protective level of the active drug. After complicated medical history with 15 weeks of hospital stay, the patient was discharged in general good condition. Conclusions. To our knowledge, this is the first report that relates antimycotic drug dosing to a functional liver test. We provide a new approach for sepsis treatment considering liver function capacity to optimize dosage of hepatically metabolised drugs with potential hepatotoxic effects.

Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3365-3372 ◽  
Author(s):  
Oliver A. Cornely ◽  
Andrew J. Ullmann ◽  
Meinolf Karthaus
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
High Risk Patient ◽  
Risk Groups ◽  
Hematologic Malignancies ◽  
Antifungal Prophylaxis ◽  
Severe Neutropenia ◽  
Evidence Based ◽  
Cell Transplants

Invasive fungal infection is an increasing source of morbidity and mortality in patients with hematologic malignancies, particularly those with prolonged and severe neutropenia (absolute white blood cell count < 100/μL). Early diagnosis of invasive fungal infection is difficult, suggesting that antifungal prophylaxis could be the best approach for neutropenic patients undergoing intensive myelosuppressive chemotherapy. Consequently, antifungal prophylaxis has been extensively studied for more than 20 years. Nonabsorbable polyenes reduce superficial mycoses but are not effective in preventing or treating invasive fungal infections. Intravenous amphotericin B and the newer azoles were used in numerous clinical trials, but the value of antifungal prophylaxis in defined risk groups with cancer is still open to discussion. Recipients of allogeneic stem cell transplants and patients with a relapsed leukemia are high-risk patient populations. In addition, certain risk factors are well defined, for example, neutropenia more than 10 days, corticosteroid therapy, sustained immunosuppression, and graft-versus-host disease. In contrast to study efforts, evidence-based recommendations on the clinical use of antifungal prophylaxis according to risk groups are rare. The objective of this review of 50 studies accumulating more than 9000 patients is to assess evidence-based criteria with regard to the efficacy of antifungal prophylaxis in neutropenic cancer patients.

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