National Institutes of Health Awards Arkansas Children’s Research Institute, Children’s Hospital of Philadelphia $9.7 Million for Antifungal Therapy Study

(LITTLE ROCK, AR.) Aug. 29, 2022 – Scientists at Arkansas Children’s Research Institute and Children’s Hospital of Philadelphia will use $9.7 million in funding from the National Institutes of Health to conduct a first-of-its-kind study to determine if a shorter course of therapy effectively treats uncomplicated candidemia, the most common invasive fungal disease in children.

The seven-year project will help researchers understand whether children with uncomplicated candidemia that has improved after seven days of antifungal therapy can stop treatment at that time or should continue for another seven days which is the current standard of care. This research marks the first randomized, controlled trial to define the optimal duration of therapy for any invasive fungal disease in any age group.

While invasive candidiasis can have severe and potentially deadly consequences in immunocompromised patients, much of the invasive candidiasis diagnosed in children is uncomplicated candidemia. Unlike in adults, the vast majority of children with uncomplicated candidemia improve relatively quickly on appropriate antifungal therapy. However, in certain cases, candidemia can result in a more complicated infection that impacts other organs and the musculoskeletal system. Currently, the minimal duration of therapy for candidemia is 14 days regardless of whether it is complicated or uncomplicated. This standard approach can result in unnecessarily long durations of antifungal therapy for uncomplicated candidemia.

Researchers will examine the benefits and consequences of the shorter-term treatment of uncomplicated candidemia and assess whether a new molecular biomarker that already allows for rapid diagnoses of children with invasive candidiasis can also indicate the shorter course of therapy may be a better option for patients.

“This study will build a foundation for improved guidelines that allow us to treat children more rapidly, reduce the medicine they need and get them back to thriving quickly,” said William Steinbach, MD, the study’s co-principal investigator, pediatrician in chief at Arkansas Children’s and chair of the Department of Pediatrics and associate dean for Child Health at the University of Arkansas for Medical Sciences (UAMS). “The results also will inform future trials in adults and allow us to change guidelines for care of all patients with these diseases.”

Also leading the study will be Brian Fisher, DO, MSCE, MPH, an attending physician and director of the Pediatric Infectious Diseases Fellowship Training Program at Children’s Hospital of Philadelphia.

“In addition to being one of the first clinical trials to compare different durations of therapy for invasive fungal disease, this study will also utilize a novel outcome measure referred to as Desirability of Outcome Ranking or ‘DOOR,’” Fisher said. “This outcome approach, developed by Dr. Scott Evans at the George Washington University, captures both the benefits and consequences of an intervention which makes it an ideal measure for a trial assessing different durations of antifungal therapy.”

Randomized clinical trials and studies of bacterial infections such as pneumonia, urinary tract infections and Gram-negative bacteremia have proven that shorter durations of therapy are effective and spare patients some of the unintended consequences of continued anti-infective exposures.

The study will leverage the International Pediatric Fungal Network (PFN), a 55-site international research consortium focused on defining the best ways to diagnose and treat deadly invasive fungal infections in children. Drs. Steinbach and Fisher co-lead the network, with a study coordinating center now housed at Arkansas Children’s Research Institute. Its data coordinating center is located at Children’s Hospital of Philadelphia.