scholarly journals Liquid biopsy for infectious diseases: Sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

2018 ◽  
Author(s):  
David K. Hong ◽  
Timothy A. Blauwkamp ◽  
Mickey Kertesz ◽  
Sivan Bercovici ◽  
Cynthia Truong ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Invasive Fungal Disease ◽  
Invasive Fungal Infections ◽  
High Morbidity ◽  
Non Invasive ◽  
Treatment Information ◽  
Life Threatening ◽  
Pathogen Dna ◽  
Microbiologic Diagnosis ◽  
Free Plasma

AbstractDiagnosis of life-threatening deep-seated infections currently requires invasive sampling of the infected tissue to provide a microbiologic diagnosis. These procedures can lead to high morbidity in patients and add to healthcare costs. Here we describe a novel next-generation sequencing assay that was used to detect pathogen-derived cell-free DNA in peripheral blood of patients with biopsy-proven invasive fungal infections. The non-invasive nature of this approach could provide rapid, actionable treatment information for invasive fungal infections when a biopsy is not possible.

scholarly journals The role of chest ultrasound in diagnosing invasive fungal infections in acute leukemia patients

2016 ◽  
Vol 11 (2) ◽  
pp. 132-137
Author(s):  
Ana-Maria NEAGU ◽  
◽  
Ana-Maria VLĂDĂREANU ◽  
Horia BUMBEA ◽  
Diana CÎŞLEANU ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Fungal Infections ◽  
Low Cost ◽  
Empirical Therapy ◽  
Invasive Fungal Infections ◽  
Diagnostic Methods ◽  
High Morbidity ◽  
Non Invasive ◽  
Chest Ultrasound

Acute leukemia patients are the category of highest risk to develop invasive fungal infections, have high morbidity and mortality rates related to these complications. The diagnosis of these infections must be accurate and early. That is the main reason for searching non-invasive, fast, available and low cost diagnostic methods. Imagistic diagnosis is essential, computer tomography is the gold standard. Chest ultrasound has most of these characteristics, offers valuable informations and they are accurate when compared to the chest tomography results. The decision to initiate antifungal therapy is significantly better than the empirical therapy, having lower mortality rate among these patients.

Recent advances in the treatment of life-threatening, invasive fungal infections

2013 ◽  
Vol 14 (17) ◽  
pp. 2361-2374 ◽  
Author(s):  
Richard H Drew ◽  
Mary L Townsend ◽  
Melanie W Pound ◽  
Steven W Johnson ◽  
John R Perfect
Keyword(s):  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Recent Advances ◽  
Life Threatening

scholarly journals Multiplex PCR Based Strategy for Detection of Fungal Pathogen DNA in Patients with Suspected Invasive Fungal Infections

2020 ◽  
Vol 6 (4) ◽  
pp. 308
Author(s):  
Joana Carvalho-Pereira ◽  
Filipa Fernandes ◽  
Ricardo Araújo ◽  
Jan Springer ◽  
Juergen Loeffler ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Fungal Species ◽  
Cross Reactivity ◽  
Invasive Fungal Infections ◽  
Clinical Samples ◽  
Correct Identification ◽  
Colony Pcr ◽  
Pcr Multiplex ◽  
Pathogen Dna ◽  
Species Specific

A new and easy polymerase chain reaction (PCR) multiplex strategy, for the identification of the most common fungal species involved in invasive fungal infections (IFI) was developed in this work. Two panels with species-specific markers were designed, the Candida Panel for the identification of Candida species, and the Filamentous Fungi Panel for the identification of Aspergillus species and Rhizopusarrhizus. The method allowed the correct identification of all targeted pathogens using extracted DNA or by colony PCR, showed no cross-reactivity with nontargeted species and allowed identification of different species in mixed infections. Sensitivity reached 10 to 1 pg of DNA and was suitable for clinical samples from sterile sites, with a sensitivity of 89% and specificity of 100%. Overall, the study showed that the new method is suitable for the identification of the ten most important fungal species involved in IFI, not only from positive blood cultures but also from clinical samples from sterile sites. The method provides a unique characteristic, of seeing the peak in the specific region of the panel with the correct fluorescence dye, that aids the ruling out of unspecific amplifications. Furthermore, the panels can be further customized, selecting markers for different species and/or resistance genes.

scholarly journals Liquid biopsy for infectious diseases: sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

2018 ◽  
Vol 92 (3) ◽  
pp. 210-213 ◽  
Author(s):  
David K. Hong ◽  
Timothy A. Blauwkamp ◽  
Mickey Kertesz ◽  
Sivan Bercovici ◽  
Cynthia Truong ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Liquid Biopsy ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Pathogen Dna ◽  
Free Plasma

scholarly journals Combination Treatment of Invasive Fungal Infections

2005 ◽  
Vol 18 (1) ◽  
pp. 163-194 ◽  
Author(s):  
Pranab K. Mukherjee ◽  
Daniel J. Sheehan ◽  
Christopher A. Hitchcock ◽  
Mahmoud A. Ghannoum
Keyword(s):  
Treatment Outcome ◽  
Combination Therapy ◽  
Fungal Infections ◽  
Clinical Success ◽  
Treatment Strategies ◽  
Historical Review ◽  
Invasive Fungal Infections ◽  
High Morbidity ◽  
Interpretation Criteria

SUMMARY The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections.

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)

Overview of the lipid formulations of amphotericin B

2002 ◽  
Vol 49 (suppl_1) ◽  
pp. 31-36 ◽  
Author(s):  
Bertrand Dupont
Keyword(s):  
Effective Dose ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Limiting Factors ◽  
Double Blind Study ◽  
Double Blind ◽  
Life Threatening ◽  
The Impact ◽  
Lipid Formulations

Abstract Invasive fungal infections have been increasingly recognized as a major cause of morbidity and mortality in the immunocompromised host. Amphotericin B has a broad spectrum and has remained the drug of choice for life-threatening invasive fungal infections. However, adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose: the prescription of amphotericin B is a compromise between toxicity and efficacy. Lipid formulations offer a better therapeutic index by circumscribing amphotericin B toxicity. Three lipid formulations are available in most countries: AmBisome, the only true liposome; Abelcet, with a ribbon-like structure; and Amphocil/Amphotec, composed of disc-like structures. All these formulations contain amphotericin B, but they differ in shape, size, reticuloendothelial clearance, Cmax, AUC and visceral diffusion. The impact of these differences in pharmacokinetics and pharmacodynamics on clinical efficacy is still unclear. Efficacy has been shown in neutropenic patients with fever of unknown origin, systemic candidosis, invasive aspergillosis, cryptococcal meningitis and a variety of other difficult-to-treat mycoses, such as Fusarium or Zygomycetes infections. The effective dose may vary from one formulation to the other and is c. 3–5 mg/kg/day. All formulations are less nephrotoxic than amphotericin B. In one randomized double-blind study, AmBisome 3 or 5 mg/kg/day was less nephrotoxic and gave fewer infusion-related events than Abelcet 5 mg/kg/day. Abelcet induces fewer infusion-related side effects than Amphocil. All formulations seem at least as effective as amphotericin B. In some patients with life-threatening mycosis who failed treatment with, or were intolerant to, amphotericin B, the lipid formulations were effective. Further studies with comparable selected high-risk patients are warranted to clarify the usefulness and the indications of each of the formulations. Cost is a factor limiting prescription in many institutions, where use is often restricted to patients intolerant of, or refractory to, amphotericin B.

scholarly journals Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

2021 ◽  
Vol 28 (1) ◽  
pp. 837-841
Author(s):  
Omar Alkharabsheh ◽  
Alhareth Alsayed ◽  
Diana M. Morlote ◽  
Amitkumar Mehta
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Case Reports ◽  
Invasive Fungal Infections ◽  
Lymphocytic Leukemia ◽  
High Morbidity ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitors

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib.

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