Browsing by Subject "antifungal prophylaxis"

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    Blood Aspergillus PCR: The Good, the Bad, and the Ugly.
    (Journal of fungi (Basel, Switzerland), 2020-01) Egger, Matthias; Jenks, Jeffrey D; Hoenigl, Martin; Prattes, Juergen
    Invasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and improving the diagnostic process are ambitiously searched for. In this context, polymerase chain reaction (PCR) may represent a potential candidate. Its additional value and benefits in diagnosis have been demonstrated and are scientifically established. Nevertheless, standardized and widespread usage is sparse because several factors influence diagnostic quality and need to be considered in order to optimize diagnostic performance and outcome. In the following review, the current role of PCR in the diagnosis of IA is explored, with special focus on the strengths and limitations of PCR in different settings.
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    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 A

    Background

    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.
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    Microbiology and Risk Factors for Hospital-Associated Bloodstream Infections Among Pediatric Hematopoietic Stem Cell Transplant Recipients.
    (Open forum infectious diseases, 2020-04) Akinboyo, Ibukunoluwa C; Young, Rebecca R; Spees, Lisa P; Heston, Sarah M; Smith, Michael J; Chang, Yeh-Chung; McGill, Lauren E; Martin, Paul L; Jenkins, Kirsten; Lugo, Debra J; Hazen, Kevin C; Seed, Patrick C; Kelly, Matthew S
    Background:Children undergoing hematopoietic stem cell transplantation (HSCT) are at high risk for hospital-associated bloodstream infections (HA-BSIs). This study aimed to describe the incidence, microbiology, and risk factors for HA-BSI in pediatric HSCT recipients. Methods:We performed a single-center retrospective cohort study of children and adolescents (<18 years of age) who underwent HSCT over a 20-year period (1997-2016). We determined the incidence and case fatality rate of HA-BSI by causative organism. We used multivariable Poisson regression to identify risk factors for HA-BSI. Results:Of 1294 patients, the majority (86%) received an allogeneic HSCT, most commonly with umbilical cord blood (63%). During the initial HSCT hospitalization, 334 HA-BSIs occurred among 261 (20%) patients. These were classified as gram-positive bacterial (46%), gram-negative bacterial (24%), fungal (12%), mycobacterial (<1%), or polymicrobial (19%). During the study period, there was a decline in the cumulative incidence of HA-BSI (P = .021) and, specifically, fungal HA-BSIs (P = .002). In multivariable analyses, older age (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], 1.01-1.06), umbilical cord blood donor source (vs bone marrow; IRR, 1.69; 95% CI, 1.19-2.40), and nonmyeloablative conditioning (vs myeloablative; IRR, 1.85; 95% CI, 1.21-2.82) were associated with a higher risk of HA-BSIs. The case fatality rate was higher for fungal HA-BSI than other HA-BSI categories (21% vs 6%; P = .002). Conclusions:Over the past 2 decades, the incidence of HA-BSIs has declined among pediatric HSCT recipients at our institution. Older age, umbilical cord blood donor source, and nonmyeloablative conditioning regimens are independent risk factors for HA-BSI among children undergoing HSCT.
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    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 R

    Background

    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.