Browsing by Author "Nguyen, M Hong"
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Item Open Access A Mycoses Study Group International Prospective Study of Phaeohyphomycosis: An Analysis of 99 Proven/Probable Cases.(Open forum infectious diseases, 2017-01) Revankar, Sanjay G; Baddley, John W; Chen, Sharon C-A; Kauffman, Carol A; Slavin, Monica; Vazquez, Jose A; Seas, Carlos; Morris, Michele I; Nguyen, M Hong; Shoham, Shmuel; Thompson, George R; Alexander, Barbara D; Simkins, Jacques; Ostrosky-Zeichner, Luis; Mullane, Kathleen; Alangaden, George; Andes, David R; Cornely, Oliver A; Wahlers, Kerstin; Lockhart, Shawn R; Pappas, Peter GBackground
Phaeohyphomycosis is infection caused by dematiaceous, or darkly pigmented, fungi. The spectrum of disease is broad, and optimal therapy remains poorly defined. The Mycoses Study Group established an international case registry of patients with proven/probable phaeohyphomycosis with the goal of improving the recognition and management of these infections.Methods
Patients from 18 sites in 3 countries were enrolled from 2009-2015. Cases were categorized as local superficial, local deep (pulmonary, sinus, osteoarticular infections), and disseminated infections. End points were clinical response (partial and complete) and all-cause mortality at 30 days and end of follow-up.Results
Of 99 patients, 32 had local superficial infection, 41 had local deep infection, and 26 had disseminated infection. The most common risk factors were corticosteroids, solid organ transplantation, malignancy, and diabetes. Cultures were positive in 98% of cases. All-cause mortality was 16% at 30 days and 33% at end of follow-up, and 18 of 26 (69%) with dissemination died. Itraconazole was most commonly used for local infections, and voriconazole was used for more severe infections, often in combination with terbinafine or amphotericin B.Conclusions
Phaeohyphomycosis is an increasingly recognized infection. Culture remains the most frequently used diagnostic method. Triazoles are currently the drugs of choice, often combined with other agents. Further studies are needed to develop optimal therapies for disseminated infections.Item Open Access Coronavirus Disease 2019-Associated Invasive Fungal Infection.(Open forum infectious diseases, 2021-12) Baddley, John W; Thompson, George R; Chen, Sharon C-A; White, P Lewis; Johnson, Melissa D; Nguyen, M Hong; Schwartz, Ilan S; Spec, Andrej; Ostrosky-Zeichner, Luis; Jackson, Brendan R; Patterson, Thomas F; Pappas, Peter GCoronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections.Item Open Access Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical Trial Design: Unintended Consequences for Prevention Trials?(Open forum infectious diseases, 2021-10) Wingard, John R; Alexander, Barbara D; Baden, Lindsey R; Chen, Min; Sugrue, Michele W; Leather, Helen L; Caliendo, Angela M; Clancy, Cornelius J; Denning, David W; Marty, Francisco M; Nguyen, M Hong; Wheat, L Joseph; Logan, Brent R; Horowitz, Mary M; Marr, Kieren ABackground
Consensus definitions for the diagnosis of invasive fungal diseases (IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical trials, for instance by increasing biomarker cutoff limits to define positivity. To date, there is a paucity of data as to the impact of the revised definitions on clinical trials.Methods
In this study, we sought to determine the impact of the new definitions on classifying invasive aspergillosis (IA), the most common invasive mold disease in immunocompromised patients. We reclassified 226 proven and probable IA cases plus 139 possible IFD cases in the Aspergillus Technology Consortium (AsTeC) and in an antifungal prophylaxis trial (BMT CTN 0101) using the new criteria.Results
Fewer cases met the more stringent diagnostic 2020 criteria after applying the reclassification criteria to define probable IA. Of 188 evaluable probable cases, 41 (22%) were reclassified to 40 possible IA and 1 probable IFD. Reclassification to possible IFD occurred in 22% of hematologic malignancy (HM) patients, 29% of hematopoietic cell transplant (HCT) patients, and in no lung transplant (LT) patients. Date of diagnosis was established a median (range) of 3 (1-105) days later in 15% of probable IA cases using the new criteria. Applying the new definitions to the BMT CTN 0101 trial, the power to detect the same odds ratio decreased substantially.Conclusions
The updated IA consensus definitions may impact future trial designs, especially for antifungal prophylaxis studies.Item Open Access Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.(PloS one, 2015-01) Brasier, Allan R; Zhao, Yingxin; Spratt, Heidi M; Wiktorowicz, John E; Ju, Hyunsu; Wheat, L Joseph; Baden, Lindsey; Stafford, Susan; Wu, Zheng; Issa, Nicolas; Caliendo, Angela M; Denning, David W; Soman, Kizhake; Clancy, Cornelius J; Nguyen, M Hong; Sugrue, Michele W; Alexander, Barbara D; Wingard, John RInvasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment for hematologic malignancy. Upon further validation, early detection of probable IPA in leukemia treatment will provide opportunities for earlier interventions and interventional clinical trials.Item Open Access Invasive Aspergillosis as an Under-recognized Superinfection in COVID-19.(Open forum infectious diseases, 2020-07) Thompson Iii, George R; Cornely, Oliver A; Pappas, Peter G; Patterson, Thomas F; Hoenigl, Martin; Jenks, Jeffrey D; Clancy, Cornelius J; Nguyen, M HongPulmonary aspergillosis has been increasingly reported following severe respiratory viral infections. Millions have been infected by SARS-CoV-2, placing large numbers of patients at-risk for COVID-19 associated pulmonary aspergillosis (CAPA). Prompt recognition of this syndrome and is paramount to improve outcomes.Item Open Access Real-world Use of Mold-Active Triazole Prophylaxis in the Prevention of Invasive Fungal Diseases: Results From a Subgroup Analysis of a Multicenter National Registry.(Open forum infectious diseases, 2023-09) Nguyen, M Hong; Ostrosky-Zeichner, Luis; Pappas, Peter G; Walsh, Thomas J; Bubalo, Joseph; Alexander, Barbara D; Miceli, Marisa H; Jiang, Jeanette; Song, Yi; Thompson, George RBackground
Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed the real-world use of mold-active triazoles (MATs) for the prevention of IFDs.Methods
This subgroup analysis of a multicenter, observational, prospective registry in the United States from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient characteristics and patterns of MAT use. Exploratory assessments included the frequency of breakthrough IFDs and MAT-related adverse drug reactions (ADRs).Results
A total of 1177 patients (256 isavuconazole, 397 posaconazole, 272 voriconazole, and 252 multiple/sequenced MATs at/after index/enrollment) were included in the prophylaxis subgroup analysis. Patient characteristics were similar across MAT groups, but risk factors varied. Hematological malignancy predominated (76.5%) across all groups. Breakthrough IFDs occurred in 7.1% (73/1030) of patients with an investigator's assessment (5.0% [11/221] isavuconazole; 5.3% [20/374] posaconazole; 4.0% [9/226] voriconazole; and 15.8% [33/209] multiple/sequenced MATs). Aspergillus (29.5% [18/61]) and Candida (36.1% [22/61]) species were the most common breakthrough pathogens recovered. ADRs were reported in 14.1% of patients, and discontinuation of MATs due to ADRs was reported in 11.1% of patients (2.0% [5/245] isavuconazole; 8.2% [30/368] posaconazole; and 10.1% [27/267] voriconazole).Conclusions
Breakthrough IFDs were uncommon in patients who received MATs for prophylaxis. Candida and Aspergillus species were the most commonly reported breakthrough pathogens. The discontinuation of MATs due to ADRs was infrequent. These findings support prophylactic strategies with isavuconazole, posaconazole, and voriconazole in high-risk patients.