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)

Rapid Detection of Invasive Fungal Infections in Hemato-Oncological Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1468-1468 ◽  
Author(s):  
Christine Landlinger ◽  
Lenka Baskova ◽  
Sandra Preuner ◽  
Martine Van Grotel ◽  
Nico G. Hartwig ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Fungal Species ◽  
Invasive Fungal Infections ◽  
Antifungal Treatment ◽  
Test Panel ◽  
Clinical Specimens ◽  
Oncological Patients ◽  
Fungal Dna

Abstract Invasive fungal infections (IFI) play an increasingly important role as life-threatening complications in immunocompromised patients. Recent surveys show that annually 450.000 patients suffer from invasive mycoses worldwide. Early application of antimycotic agents is an essential prerequisite for successful therapy. However, standardized diagnostic techniques permitting rapid, and sensitive screening for the clinically relevant fungi have been lacking. Moreover, the increasing incidence of invasive infections caused by hitherto uncommon fungal species requires diagnostic tests with very broad specificity. We developed a panfungal real-time PCR (RQ-PCR) screening assay targeting the highly conserved region of the 28S ribosomal multicopy gene. Universal primers and probes for two test panels in two separate PCR reactions were established facilitating the detection and quantitative assessment of a broad range of pathogenic fungi. The reaction of test panel I covers a range of moulds including species from the fungal genera Aspergillus, Fusarium, Penicillium, Cladosporium, and Scedosporium. The test panel of reaction II facilitates the detection of yeasts from the genera Candida, Cryptococcus, Malassezia, and Trichosporon as well as Zygomycetes (Mucor, Rhizopus, Rhizomucor, Absidia), and other emerging fungal pathogens. In total, more than 80 human pathogenic fungal species can be detected and quantified. The detection limit of the panfungal RQ-PCR assay in clinical specimens was shown to be in the range of 1 fg fungal DNA, which corresponds to a fraction of a single fungal genome. To assess the clinical applicability of the technique, more than 1.000 clinical specimens derived from 144 well-documented pediatric hemato-oncological patients at high risk of invasive fungal infection were analyzed. The specimens investigated included predominantly serial plasma samples (n>950), and a small number of other materials including bronchotracheal secretion, bronchoalveolar lavage, lung biopsy, liver biopsy, and cerebrospinal fluid. In about 65% of the patients analyzed, evidence of fungemia was found in serial specimens. In a large proportion of these patients (31%), both reactions revealed positive results indicating mixed fungal infections. Isolated positivity of reaction I or II was observed in 29% and 5%, respectively. The high percentage of patients with PCR-detectable fungal DNA in normally sterile clinical specimens raises questions about the interpretation and clinical relevance of the findings. The possible occurrence of contamination was largely excluded by the implementation of multiple controls at all stages of the diagnostic process. The great sensitivity of RQ-PCR analysis may permit the detection of low-level fungal DNAemia which may not generally reflect an imminent risk of severe fungal disease. Interpretation of the molecular findings therefore has to be performed with caution. Current evaluation of the RQ-PCR data in relation to the EORTC definitions of proven, probable and possible invasive fungal infection, which are based on clinical criteria, host factors, and microbiological criteria, revealed a very good correlation. Indeed, most patients with repeatedly positive RQ-PCR results, which had been generated in a double-blind fashion, received antifungal treatment on the basis of other findings. The assay presented is a powerful tool for rapid and economic screening of IFIs and ongoing analyses are expected to reveal how the technique could be implemented in clinical diagnostics to support timely onset and management of antifungal treatment.

Invasive fungal infections are associated with severe depletion of circulating RANTES

2005 ◽  
Vol 54 (11) ◽  
pp. 1017-1022 ◽  
Author(s):  
Michael Ellis ◽  
Basel al-Ramadi ◽  
Ulla Hedström ◽  
Hussain Alizadeh ◽  
Victor Shammas ◽  
...  
Keyword(s):  
T Cell ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Host Response ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Time Of Death ◽  
Haematological Malignancies ◽  
Platelet Counts ◽  
The Mean

Serum RANTES (regulated on activation, normal T-cell expressed and secreted) concentrations were measured in 14 patients who had haematological malignancies and developed invasive fungal infections (three of them definite, eight probable and three possible). RANTES levels fell substantially from pre-chemotherapy values at the start of and throughout the fungal infection, and recovered in patients who survived the fungal infection. However, in patients who died from the invasive fungal infection, RANTES levels did not recover. For survivors the mean ± sd levels for RANTES were 7656 ± 877 pg ml−1 on the day prior to chemotherapy, 3723 ± 2443 pg ml−1 on the first day of fungal infection diagnosis (significantly different from baseline; P = 0.001) and 9078 ± 2256 pg ml−1 at recovery from the fungal infection (significantly different from lowest value; P < 0.0001). Platelet counts were closely correlated with the RANTES levels (r = 0.63, P < 0.001). The RANTES concentrations for the three patients who died were similar to those who survived at all equivalent timepoints, but were significantly lower at the time of death (792 ± 877) compared to the values at recovery for survivors (P = 0.005). The finding that patients who died from an invasive fungal infection had very low platelet counts and RANTES concentrations suggests that these could play a role in host response to such infections.

scholarly journals Fungal Infections in Liver Transplant Recipients

2021 ◽  
Vol 7 (7) ◽  
pp. 524
Author(s):  
Michael Scolarici ◽  
Margaret Jorgenson ◽  
Christopher Saddler ◽  
Jeannina Smith
Keyword(s):  
Liver Transplantation ◽  
Liver Transplant ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Morbidity And Mortality ◽  
Transplant Recipients ◽  
Liver Transplant Recipients

Invasive fungal infections (IFIs) are one of the most feared complications associated with liver transplantation, with high rates of morbidity and mortality. We discuss the most common invasive fungal infections in the setting of liver transplant, including Candida, Aspergillus, and Cryptococcal infections, and some less frequent but devastating mold infections. Further, we evaluate the use of prophylaxis to prevent invasive fungal infection in this population as a promising mechanism to reduce risks to patients after liver transplant.

Prophylactic and Preemptive Anti-Fungal Therapy after Cord Blood Transplantation: A Retrospective Analyses of 188 Adult Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5320-5320
Author(s):  
Yoshiko Matsuhashi ◽  
Shinsuke Takagi ◽  
Hisashi Yamamoto ◽  
Daisuke Kato ◽  
Naofumi Matsuno ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Cord Blood ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Cord Blood Transplantation ◽  
Invasive Fungal Infections ◽  
Blood Transplantation ◽  
Group A ◽  
Group B ◽  
Anti Fungal

Abstract Background: Therapeutic outcomes for hematological diseases have recently been markedly improved due to the introduction of hematopoietic stem cell transplantation (HSCT), improvement of therapeutic regimens, and advancement of support therapy. Although invasive fungal infections have been one of the major causes of morbidity and mortality after cord blood transplantation(CBT), proper prophylactic and therapeutic approach to them has not been clearly established yet. To address this, we performed retrospective analysis to assess the effectiveness and safety of various antifungal agents for prevention and treatment of invasive fungal infections. Patients and Methods: Medical records of a total of 188 patients who underwent umbilical CBT at Toranomon hospital between March 2002 and December 2005 were reviewed. The diagnosis included AML (n=53), ML (n=32), MDS (n=25), ALL (n=24), ATL (n=22), CML (n=7), AA (n=5), MM (n=3), and others (n=17). The median age was 54 (range; 17–79). The conditioning regimen consisted of fludarabine (125mg/m2), melphalan (80 mg/m2) and 4 Gy TBI for most of the patients. The incidence of breakthrough invasive fungal infection within 50 days after transplant was analysed. Results: Forty-eight of the 188 were administered prophylactic anti-fungal agents other than fluconazole (FLCZ) due to prior mold infection, intorelant to FLCZ, and so on, were excluded. Remaining 140 patients who received FLCZ categolized into 2 groups; those who had empirically switched FLCZ to micafungin (MCFG) and/or amphotericin B (AMPH) and/or itraconazole (ITCZ) capsule at the first sign of infection (group A, n=69), and those who had continued FLCZ (group B, n=71). Four breakthrough invasive fungal infections were observed, 3 of them were invasive pulmonary aspergillosis (IPA), and 1 of them was tricosporon sepsis. Interestingly, all of these 4 were in group B, whereas no breakthrough infections were observed in those who were in group A. All 3 diagnosed IPA died of its exacerbation despite MCFG and/or AMPH treatment. Conclusion: Proper administration of prophylactic anti-fungal agents can reduce the incidence of invasive fungal infection early after CBT. Although FLCZ has less activity to aspergillus, prophylactic FLCZ is effective enough to prevent breakthrough fungal infection. Immediate switch to other agents at the first sign of infection, such as MCFG, AMPH, ITCZ which are active against aspergillus could be recommended to prevent breakthrough infections.

Voriconazole prophylaxis in leukemic patients: A retrospective single-center study

2019 ◽  
Vol 26 (4) ◽  
pp. 873-881
Author(s):  
Vivian Bui ◽  
Sandra AN Walker ◽  
Marion Elligsen ◽  
Anju Vyas ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Retrospective Chart Review ◽  
Liver Function Tests ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Acute Myeloid

Background Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. Objectives The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. Methods A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. Results Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%–3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). Conclusions Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.

Invasive fungal infections in Colombian patients with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (7) ◽  
pp. 1116-1122 ◽  
Author(s):  
Y Santamaría-Alza ◽  
J Sánchez-Bautista ◽  
J F Fajardo-Rivero ◽  
C L Figueroa
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Fungal Infection ◽  
Disease Activity ◽  
Invasive Fungal Infection ◽  
Lupus Erythematosus ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Bivariate Analysis ◽  
Systemic Lupus ◽  
Pericardial Disease

Introduction Systemic lupus erythematosus is an autoimmune disease with multi-organ involvement. Complications, such as invasive fungal infections usually occur in patients with a greater severity of the disease. Objective The objective of this study was to determine the prevalence and risk variables associated with invasive fungal infections in a Colombian systemic lupus erythematosus population. Materials and methods A cross-sectional, retrospective study that evaluated patients with systemic lupus erythematosus for six years. The primary outcome was invasive fungal infection. Descriptive, group comparison and bivariate analysis was performed using Stata 12.0 software. Results Two hundred patients were included in this study; 84.5% of the patients were women and the median age was 36 years; 68% of the subjects had haematological complications; 53.3% had nephropathy; 45% had pneumopathy and 28% had pericardial impairment; 7.5% of patients had invasive fungal infections and the most frequently isolated fungus was Candida albicans. Pericardial disease, cyclophosphamide use, high disease activity, elevated ESR, C3 hypocomplementemia, anaemia and lymphopenia had a significant association with invasive fungal infection ( P < 0.05). Conclusions We describe for the first time the prevalence of invasive fungal infection in a Colombian population with systemic lupus erythematosus, which was higher than that reported in other latitudes. In this population the increase in disease activity, the presence of pericardial impairment and laboratory alterations (anaemia, lymphopenia, increased ESR and C3 hypocomplementemia) are associated with a greater possibility of invasive fungal infections. Regarding the use of drugs, unlike other studies, in the Colombian population an association was found only with the previous administration of cyclophosphamide. In addition, patients with invasive fungal infections and systemic lupus erythematosus had a higher prevalence of mortality and hospital readmission compared with patients with systemic lupus erythematosus without invasive fungal infection.

scholarly journals Invasive Fungal Infections in Canada from 1992 to 1994

1998 ◽  
Vol 9 (6) ◽  
pp. 347-352 ◽  
Author(s):  
LE Nicolle ◽  
C Rotstein ◽  
AM Bourgault ◽  
G St-Germain ◽  
G Garber ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Histoplasma Capsulatum ◽  
Fungal Infections ◽  
Case Fatality ◽  
Invasive Fungal Infections ◽  
Immunodeficiency Virus ◽  
Clinical Surveillance ◽  
Record Review ◽  
Major Pathogens

PURPOSE: To describe the frequency, characteristics and impact of invasive fungal infection in Canada.METHODS: Nominal case reporting with standardized data collection from selected sites across Canada. Cases were found primarily through laboratory review with supplementation by record review and clinical surveillance at some sites.RESULTS: The frequency of invasive fungal infection varied from 3.54 to 6.64/100,000 population per year.Candidaspecies were responsible for 66% of all reports; 80% of candidal infections were bloodstream isolates.Crytococcus neoformans,Aspergillusspecies andHistoplasma capsulatumeach accounted for 5% to 10% of cases, and all other organisms less than 5% each. Human immunodeficiency virus infection was an important comorbidity for cryptococcus and histoplasma infections, and was associated with increased mortality for only histoplasma infections. Geographical variation of histoplasma, blastomyces and coccidioidomyces infection was confirmed. Case fatality was high for all invasive fungal infections, except coccidioidomycosis, blastomycosis and sporotrichosis.CONCLUSIONS:Candidaspecies infections are the major pathogens in invasive fungal infections in Canada; all other species occur relatively infrequently. The potential for therapeutic intervention to limit mortality requires further assessment.

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