Identification and in Vitro Susceptibility Pattern of Fungal Pathogens in Immunocompromised Patients with invasive Fungal Infections

2021 ◽  
Vol 30 (3) ◽  
pp. 127-134
Author(s):  
Shaimaa A.S. Selem ◽  
Neveen A. Hassan ◽  
Mohamed Z. Abd El-Rahman ◽  
Doaa M. Abd El-Kareem
Keyword(s):  
Intensive Care ◽  
Fungal Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
University Hospitals ◽  
Vitek 2

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.

Molecular diagnosis and antifungal resistance and biofilm production profiles among Candida species isolated from immunocompromised patients at Menoufia University Hospitals

2020 ◽  
Vol 29 (3) ◽  
pp. 37-45
Author(s):  
Mabrouk M Ghonaim ◽  
Azza Z. Labeeb ◽  
Alyaa I. Eliwa ◽  
Eman H. Salem
Keyword(s):  
Candida Species ◽  
Biofilm Formation ◽  
Antifungal Susceptibility ◽  
High Sensitivity ◽  
Antifungal Resistance ◽  
Common Source ◽  
Immunocompromised Patients ◽  
University Hospitals ◽  
Biofilm Production ◽  
Vitek 2

Background: Accurate and rapid identification of Candida species is necessary for proper diagnosis and treatment of candidiasis due to emergences of drug-resistant strains especially among immunocompromised patients. Objectives: Identification of Candida clinical isolates to the species level using different phenotypic and molecular methods. Biofilm-forming ability and antifungal resistance were also studied. Methodology: Sixty-nine Candida strains were isolated from 220 immunocompromised patients. Identification was performed using chromogenic Candida agar, VITEK 2 system and multiplex polymerase chain reaction (PCR). Biofilm formation was detected by the tube method and antifungal susceptibility was tested using the VITEK2 system. Results: The most common source of Candida isolates was from urine (33.3%) and ICUs (56.6%). VITEK 2 system detected 9 spp.: C. albicans (34.8%), C. tropicalis (21.7%), C. famata (8.7%), C. lusitaniae (7.2%), C. cruzi (7.2%), C. ciferri (5.8%), C. dubliniensis (5.8%), C. parapsilosis (5.8 %) and C. glabrata. Candida isolates showed high resistance to flucytocine (49.3%), and high sensitivity to fluconazole, micafungin, voriconazole and caspofungin (88.4%, 81.2% and 81.2 % respectively). Only 30.4% of all Candida isolates were biofilm producers. There was a positive relationship between antifungal resistance and biofilm formation among Candida isolates. Conclusion: C. albicans was the predominant species. Chromogenic Candida agar and VITEK 2 system were valuable tests compared to PCR in speciation of Candida isolates. Antifungal susceptibility was significantly related to biofilm production and its evaluation is important for proper treatment..

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 768 Re-directed T cell therapy to control invasive aspergillosis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A816-A816
Author(s):  
Karishma Bavisi ◽  
Sebastian Wurster ◽  
Nathaniel Albert ◽  
Sattva Neelapu ◽  
Dimitrios P Kontoyiannis ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Wall ◽  
Invasive Aspergillosis ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Immunocompromised Patients ◽  
Fungal Cell ◽  
Car T Cells ◽  
Car T

BackgroundOpportunistic invasive fungal infections (IFI) are a major threat to immunocompromised populations such as patients with acute myeloid leukemia (AML) and allogenic hematopoietic stem cell transplant (HSCT) recipients(1,2). Specifically, Aspergillus fumigatus (AF) is responsible for high morbidity and mortality in cancer patients. As antifungal therapy has limited efficacy in immunocompromised patients, we sought to develop fungus-specific chimeric antigen receptor (CAR) T cells as a novel immune augmentation strategy to treat IFIs including invasive aspergillosis. To target fungal pathogens, we fused the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-ζ domains upon binding to β-1,3-glucan carbohydrates in the fungal cell wall(3). The generated Dectin-1 CAR+ T cells showed high specificity for β-1,3-gucan and inhibited the growth and branching of AF germlings in an in-vitro co-culture assay. However, we found poor efficacy of Dectin-1 CAR+ T cells against mature AF hyphae, likely due to changes in the fungal cell wall that hamper T-cellular binding to β-1,3-glucan carbohydrates. To overcome this limitation, we have recently developed an AF-specific CAR (AF-CAR) based on a monoclonal antibody which recognizes a surface epitope of mature AF hyphae.MethodsLentiviral vectors were used to generate AF-CAR expressing T cells from human peripheral blood mononuclear cells. Heat killed AF-293 hyphae was used for co-culture studies with No DNA T cells, and AF-CAR expressing T cells. Cell clusters, binding with AF hyphae were noticed in AF-CAR incubated wells whereas no such cell cluster were observed in NoDNA T cells incubated wells.ResultsWhen co-incubated with AF hyphae, AF-CAR+ T cells efficiently targeted mature hyphae and formed lytic synapses with hyphal filaments. The released cytolytic granules damage hyphae and controls branch node formation. Furthermore, exposure to AF hyphae stimulated significant upregulation of activation markers CD69 and CD154 on AF-CAR+ T cells. The activated CAR T cell secretes proinflammatory cytokines which can boost innate immune system to fight against IFI.ConclusionsIn summary, these results indicate that we have successfully generated a novel anti-Aspergillus CAR construct with good in-vitro targeting efficacy against mature AF hyphae. After thorough evaluation of fungicidal activity, cytokine response patterns, and release of cytotoxic mediators, we plan to embark on preclinical tolerability and efficacy studies in a murine model of invasive pulmonary aspergillosis. Thus, we report the production of Aspergillus specific CAR T cells to provide long term protection to immunocompromised patients, such as AML patients and HSCT recipients, from invasive Aspergillus infections.AcknowledgementsThis study was supported by NIAID-R33 AI127381.Ethics ApprovalThis study was approved by IBC committee, University of Texas MD Anderson Cancer Center, Houston, Texas, 77030.ReferencesPappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freifeld A, Anaissie EJ, Brumble LM, Herwaldt L, Ito J, Kontoyiannis DP, Lyon GM, Marr KA, Morrison VA, Park BJ, Patterson TF, Perl TM, Oster RA, Schuster MG, Walker R, Walsh TJ, Wannemuehler KA, Chiller TM. Invasive fungal infections among organ transplant recipients: results of the transplant-associated infection surveillance network (TRANSNET). Clin Infect Dis 2010;50(8):1101–11.Bhatt VR, Viola GM, Ferrajoli A. Invasive fungal infections in acute leukemia. Ther Adv Hematol 2011;2(4):231–47.Kumaresan PR, Manuri PR, Albert ND, Maiti S, Singh H, Mi T, Roszik J, Rabinovich B, Olivares S, Krishnamurthy J, Zhang L, Najjar AM, Huls MH, Lee DA, Champlin RE, Kontoyiannis DP, Cooper LJ, Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection. Proc Natl Acad Sci U S A 2014;111(29):10660–5.

scholarly journals Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 922
Author(s):  
Said El Zein ◽  
Joya-Rita Hindy ◽  
Souha S. Kanj
Keyword(s):  
Fungal Pathogens ◽  
Case Reports ◽  
Antifungal Susceptibility ◽  
Case Series ◽  
Source Control ◽  
Immunocompromised Patients ◽  
Tissue Samples ◽  
Flight Mass Spectrometry ◽  
Life Threatening

Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy.

scholarly journals Galleria mellonella for the Evaluation of Antifungal Efficacy against Medically Important Fungi, a Narrative Review

2020 ◽  
Vol 8 (3) ◽  
pp. 390 ◽  
Author(s):  
Sana Jemel ◽  
Jacques Guillot ◽  
Kalthoum Kallel ◽  
Françoise Botterel ◽  
Eric Dannaoui
Keyword(s):  
Fungal Pathogens ◽  
Galleria Mellonella ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Development Of Resistance ◽  
Antifungal Efficacy

The treatment of invasive fungal infections remains challenging and the emergence of new fungal pathogens as well as the development of resistance to the main antifungal drugs highlight the need for novel therapeutic strategies. Although in vitro antifungal susceptibility testing has come of age, the proper evaluation of therapeutic efficacy of current or new antifungals is dependent on the use of animal models. Mammalian models, particularly using rodents, are the cornerstone for evaluation of antifungal efficacy, but are limited by increased costs and ethical considerations. To circumvent these limitations, alternative invertebrate models, such as Galleria mellonella, have been developed. Larvae of G. mellonella have been widely used for testing virulence of fungi and more recently have proven useful for evaluation of antifungal efficacy. This model is suitable for infection by different fungal pathogens including yeasts (Candida, Cryptococcus, Trichosporon) and filamentous fungi (Aspergillus, Mucorales). Antifungal efficacy may be easily estimated by fungal burden or mortality rate in infected and treated larvae. The aim of the present review is to summarize the actual data about the use of G. mellonella for testing the in vivo efficacy of licensed antifungal drugs, new drugs, and combination therapies.

scholarly journals In vitro activity of four triazole antifungal drugs against clinically common and uncommon yeast species

2019 ◽  
Author(s):  
Narges Aslani ◽  
Tahereh Shokohi ◽  
Mohammad Reza Ataollahi ◽  
Saham Ansari ◽  
Yousef Gholampour ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Yeast Species ◽  
Fungal Infections ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Active Agent ◽  
Antifungal Drugs ◽  
Selection Of

Background and Purpose: Incidence of fungal infections caused by opportunistic fungal pathogens, such as yeasts and yeast-like species, has undergone an increase in otherwise healthy individuals. These pathogens account for high mortality and show reduced susceptibility to the routine antifungal drugs. Accordingly, antifungal susceptibility testing is an urgent need in the determination of the susceptibility spectrum of antifungals and selection of appropriate antifungal agents for the management of patients with fungal infection.Materials and Methods: The present study was conducted on 110 yeast strains belonging to 15 species recovered from clinical specimens. Susceptibility of the isolates to four antifungal drugs (i.e., fluconazole, itraconazole, voriconazole, and posaconazole) was tested according to the Clinical and Laboratory Standards Institute guidelines M27-A3 and M27-S4.Results: Fluconazole exhibited no activity against 4.3% (n=2) of C. albicans isolates, whereas the remaining 44 isolates had a minimum inhibitory concentration (MIC) range of 0.125-4 μg/ml. Voriconazole had the lowest geometric mean MIC (0.03 μg/ml) against all isolated yeast species, followed by posaconazole (0.07 μg/ml), itraconazole (0.10 μg/ml), and fluconazole (0.60 μg/ml). Overall, all of the isolates had reduced voriconazole MICs with a MIC range of 0.016-0.5 μg/ml, except for one isolate of C. albicans that had a MIC of 1 μg/ml. Candida haemulonii as a multidrug-resistant fungus showed a fluconazole MIC of > 64 μg/ml.Conclusion: The current study provides insight into the antifungal susceptibility profiles of clinically common and uncommon yeast species to four triazole antifungal agents. According to our findings, voriconazole was the most active agent. Awareness about antifungal susceptibility patterns is highly helpful in the selection of appropriate antifungal drugs and identification of the efficiency of the currently used agents.

Prevention, Diagnosis, and Treatment of Invasive Fungal Infections in Patients with Cancer and Neutropenia

2004 ◽  
Vol 2 (5) ◽  
pp. 455-469 ◽  
Author(s):  
Thomas A. Cumbo ◽  
Brahm H. Segal
Keyword(s):  
Fungal Infection ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Detection Methods ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Effective Prevention ◽  
Nccn Guidelines ◽  
Patients With Cancer

Invasive fungal infections are a major cause of morbidity and mortality in patients with prolonged neutropenia and in allogeneic hematopoietic stem cell transplant recipients. The degree and duration of neutropenia influence the risk of opportunistic fungal infections. Because Candida and Aspergillus species are the major causes of invasive fungal infections in neutropenic patients, the fungal section of the NCCN guidelines focus on these two pathogens. Effective prevention and therapy of invasive fungal pathogens is a priority in highly immunocompromised patients with cancer. Three strategies in preventing and treating patients at high risk for fungal infection will be considered: (1) prophylaxis; (2) empirical therapy; and (3) treatment for probable or proven fungal infection. In addition to more effective antifungal agents, growing interest has been noted in novel non-culture detection methods to facilitate early diagnosis of invasive fungal infections.

scholarly journals Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections

2020 ◽  
Vol 7 (1) ◽  
pp. 17
Author(s):  
Frederic Lamoth ◽  
Russell E. Lewis ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Antifungal Therapy ◽  
Susceptibility Testing ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Invasive Fungal Infections ◽  
Antifungal Susceptibility Testing ◽  
Candida Auris ◽  
Candida Spp ◽  
Neutropenic Patients

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.

scholarly journals Prevalence and impact of invasive fungal infections in intensive care

Critical Care ◽  
2013 ◽  
Vol 17 (S2) ◽  
Author(s):  
JM Patel ◽  
K Couper ◽  
T Melody ◽  
R O'Brien ◽  
D Parekh
Keyword(s):  
Intensive Care ◽  
Fungal Infections ◽  
Invasive Fungal Infections
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