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Research

"Clinical and Applied Research Strategies for the Prevention and Control of Fungal Diseases"

CDC # U01CK000692 (PI: Peter G. Pappas, MD)

Specific Aims

Specific Aims

Specific Aim 1: To develop and maintain reliable and innovative methods of surveillance, assessing specific risk factors and outcomes in invasive fungal infections including, but not limited to, the endemic fungi, candidiasis, cryptococcosis, and selected mold infections in varied populations

Specific Aim 2: To assess the adequacy and performance of current fungal diagnostics and to create a repository of clinical specimens from patients with proven and probably fungal infections for purposes of developing new fungal diagnostics.

Specific Aim 3: To assess the impact of public health interventions and educational strategies on the early recognition and management of invasive fungal infections

U01 Projects

  1. Prospective nationwide online registry of endemic mycoses (PI Pullen, Univ Minnesota) This ongoing study was initiated in October 2024, and has screened over 149 patients with endemic mycoses, of whom 10 have provided consent to be followed longitudinally and to be approached for other potential studies. The PI and his team are making modifications to the screening and consent process in order to more effectively identify and enroll patients into this very innovative study. If successful, this project will provide important insights into the current epidemiology and management of the endemic mycoses in the US, and would do so at a fraction of the cost of conventional surveys. (SA 1)

  2. Candida diagnostics survey (PIs Al-Obaidi, Univ Arizona; Permpalung, Johns Hopkins). This survey explorers the diagnostic capabilities and antifungal stewardship efforts relating to invasive candidiasis/candidemia at 100’s of hospitals across the United States.  The purpose of this work is to understand the strengths and weaknesses of the diagnostic infrastructure and stewardship efforts in a wide range of hospitals (community to academic) to better understand the challenges in early and accurate diagnosis of invasive Candida infections, the most common invasive fungal infection in the United States.  This study has received IRB approval and contracts have been finalized.  Study is expected to last 6 months and is scheduled to begin imminently.  (SA 2)

  3. Short course antifungal therapy for candidemia (SCAT) (PI Vazquez, Augusta Univ). This is a randomized, open-labeled clinical trial comparing short course antifungal therapy (7 days) versus standard of care (14 days) for uncomplicated candidemia. This is the first of its kind study designed to enroll approximately 150 patients in order to achieve 120 evaluable patients. 15 clinical sites across United States have been selected, and enrollment is expected to begin in late summer 2025.  The results of this trial could have significant impact on the management of uncomplicated candidemia, reflecting improved outcomes as measured by decreased days of hospitalization and its associated complications, lower healthcare costs, and lessen the emergence of resistance to echinocandin therapy. This project is approved but is still in its developmental stage, with the final protocol expected to be completed and submitted to IRB late May 2025, anticipated enrollment August 2025. (SA 1, 3).

  4. SCAT sub-study (PI Nguyen, Univ Pittsburgh) This related sub-study, headed by Dr. Nguyen, will analyze initial qualifying positive blood culture isolates from study participants focusing on the identification of secondary Candida species among the initial isolates and the presence of hetero-resistance among these isolates. This study will provide important insights into the frequency of multi-species candidemia in this patient population, as well as the presence of markers for hetero-resistance to commonly used antifungals. Findings could provide insights into clinical failure and development of high-level antifungal resistance, influencing clinical management. (SA 2, 3)

  5. Mold infection salvage study (PI Eichenberger, Emory Univ). This study is a nationwide multicenter observational study which proposes to identify patients who have failed conventional therapy for invasive mold infections including aspergillosis, mucormycosis, fusariosis, scedosporiosis, and other less common pathogens.  This study will provide important insights into the frequency and current management of these less common infections in some unusually vulnerable patients.  Conduct of the study is largely contingent on the ability to implement the Common Data Model (CDM) project outlined below.  This study is approved but has not been implemented awaiting application of the CDM (#8) as described below. (SA 1, 2)

  6. Invasive fungal disease in BTKi recipients (PI Huggins, Duke Univ). This project aims to describe the epidemiology of invasive fungal disease among Bruton’s Tyrosine Kinase inhibitors (BTKi) recipients by reviewing “big data” repositories and insurance claims from US patients.  This project will provide important insights into the risk of this morbid complication among a broad range of BTKi recipients in the US.  The study will be initiated in June 2025 and is expected to be complete within 6 months of rollout. (SA 1)

  7. Candida auris laboratory surveillance study (PI Zhang, Johns Hopkins Univ). This is a prospective lab-based study to be performed at 5-6 US clinical sites for the purpose of comparing various screening techniques for Candida auris colonization surveillance. Focus will be on high risk individuals admitted to ICUs and from nursing homes, and will compare conventional screening cultures to PCR and other molecular based diagnostics included investigational diagnostics.  This would represent the first truly prospective and multicenter comparative study of the various techniques to identify auris colonization and higher risk individuals, with the goal of identifying the most efficient and cost-effective methodology available. This study is approved and awaiting implementation in June 2025. (SA 2, 3)

  8. MSGERC registry of patients with invasive fungal infections utilizing a common data model (CDM): A prospective multisite longitudinal study (PIs Long, McGwin, McCarty, Pappas, UAB; Alexander, Duke Univ). The development of a common data model (CDM) involves the creation of a detailed computer program that we will allow for the rapid identification of patients with qualifying invasive fungal infections (cryptococcosis, endemic fungi, aspergillosis and rare molds, and invasive candidiasis). The chief purpose of this project is to gather key demographic, diagnostic, treatment, and outcome data for a wide range of individuals with invasive fungal infections in the most efficient manner possible, eliminating much of the human element related to conventional data accrual. The system utilizes hospital records from participating sites, and extracts these key data on patients identified with IFIs. This approach is well described the literature as “OMOP” (observational medical outcomes partnership). The development and implementation of this program is absolutely key to our ability to perform long-term prospective studies of IFIs in a more efficient and accurate manner. This program is being developed at UAB by Drs. McGwin and Long, and will be provided to investigators at Emory University, University of Michigan, Johns Hopkins University, Henry Ford Hospital, and Mayo Clinic Rochester as well as other initial sites for beta-testing and refinement. The first roll out relates to cryptococcosis, to be followed by mold infections, candidiasis and the endemic fungi. Once the system has been field tested and “perfected”, this program will be made available to all MSGERC participating sites in the US, of which more than 30 have shown keen interest. Currently, the study has significant potential impact on future surveillance studies, education and awareness, and public health policy.  (SA 1, 3)

  9. Correlations between airborne fungi in indoor and outdoor environments and invasive fungal infections at a tertiary care hospital (PI Clancy and Nguyen, Univ Pittsburgh). This study is a corollary to an existing CDC-funded study to the same investigators. This study will evaluate environmental airborne fungi and correlate these to incident invasive mold infections among vulnerable patients.  This study is IRB approved and expected to be completed by spring 2026. (SA 3)

  10. Defining the scope and clinical outcomes of invasive candidiasis causing by Candida auris beyond bloodstream infections (PI Al-Obaidi, Univ Arizona). This observational registry will evaluate complications of Candida auris infections as defined by non-bloodstream, “metastatic” infections. This study is unique in that it gathers data from a large number of clinical sites and will provide critical insights into the risk of metastatic involvement with auris and the most common anatomical sites involved.  Treatment and outcome data will also be captured.  The study is expected to begin enrollment in September 2025, will enroll for about 6 months, and will include both retrospective and prospective cases from across the US. (SA 1, 3)

  11. Prevalence of antifungal resistance among Aspergillus species and dermatophytes in the US (PI Wiederhold, UTHSCSA). This is an ongoing study being performed at the Fungus Testing Laboratory at UTHSCSA, and includes antifungal susceptibility testing (AFST) of all relevant specimens submitted from sites across the US, including the most common Aspergillus species and many of the cryptic Aspergillus AFST among dermatophytes is being explored, with particular focus on Trichophyton rubrum and Trichophyton indotineae, two important emerging dermatophytes in the US. These data could have tremendous importance towards informing the treatment approaches among selected patients with these infections and can provide insights into the prevalence and geographic regions most closely associated with these agents. Preliminary data for dermatophyte AFST suggests that T. indotineae and T. rubrum isolates in the US demonstrate elevated terbinafine MICs without cross-resistance to itraconazole in 85% and 18%, respectively. (SA 2, 3)

  12. Host Response Study Add-On for Mold Infection Salvage Study (MISS) (PI Steinbrink, Emory). This will be a prospective, multi-center, cohort study with the aim to define conserved elements of the host transcriptional immune response that clarify host-specific risk factors for failure of first-line antifungal treatment and breakthrough invasive mold infections.