Environmental molds are a class of fungi that are all around us, common in soil, plants, and water. Fusarium represents a large genus of fungi, with hundreds of species, seven of which can infect humans. They rarely trouble healthy people but can cause devastating, often fatal infections in patients with severely weakened immune systems. They can enter the body through the airway or skin lesions, requiring the innate and adaptive immune systems (importantly neutrophils) to clear them before they invade blood vessels, causing thrombosis and tissue death.
A new retrospective study in Transplant Infectious Disease from the Pergam Lab at Fred Hutch Cancer Center and the University of Washington examines cases spanning nine years of invasive fusariosis (IF), or infection caused by Fusarium, studying how this infection behaves in the modern era of routine antifungal prevention.
Lead author Dr. Paulina Vega weighs in: “Fusarium infection remains a leading cause of non-relapse mortality in immunocompromised patients with hematologic malignancies, and we are observing an increasing number of invasive mold infections, especially those caused by non-Aspergillus molds. Much of the available literature on fusariosis comes from regions closer to the equator, and understanding the epidemiology, environmental exposures, clinical presentations and outcomes across different geographic areas is important to helping clinicians recognize and manage these infections more effectively.”
Their study reviewed every adult cancer patient diagnosed with proven IF at Fred Hutch/UW Medical Center between July 2015 and June 2024, identifying 22 cases. Nearly half (45%) of patients lived in the greater Seattle metropolitan area, with additional cases from Central Washington (18%) and Eastern Washington (5%); the remaining cases came from out-of-state patients (California, Hawaii, Alaska, Tennessee, and Ohio) who traveled to the center for specialized cancer care. Among species identified, Fusarium fujikuroi species complex was most common (50% of cases), followed by Fusarium solani species complex (27%).
The patients at risk were mainly those with acute myeloid leukemia undergoing intensive chemotherapy, particularly re-induction treatment for relapsed disease, and nearly all were neutropenic for several weeks before infection. Fever and distinctive skin nodules were the most common warning signs of IF, and despite minimal respiratory symptoms, chest CT scans revealed pulmonary nodules in 82% of patients, underscoring the value of imaging even when patients don't complain of breathing problems.
Eighteen of 22 patients (82%) developed fusariosis while already taking preventive antifungals, most commonly the drug posaconazole, a mold-active triazole routinely given to high-risk leukemia patients. This happened largely because Fusarium shows inherently poor susceptibility to azole drugs: lab testing found posaconazole minimum inhibitory concentrations (MICs)—the drug concentration needed to stop fungal growth—were above the testable threshold in most isolates, meaning the prophylactic drug was ineffective even at high doses.
Once infection was diagnosed, treatment looked very different from prevention. All patients started on liposomal amphotericin B, a differently-acting antifungal with better in vitro activity against Fusarium. Most patients (64%) escalated to combination therapy: pairing amphotericin B with a mold-active triazole, and 59% ultimately received triple therapy, adding terbinafine, a drug that showed consistently low MICs in the lab despite being used only occasionally in clinical guidelines. Despite this aggressive, multi-drug approach, combination therapy didn't outperform monotherapy—mortality was statistically similar between groups (69% vs. 67%), highlighting how uncertain the evidence base remains for treating IF.
"Our study raises a million-dollar question: what is the best treatment for invasive fusariosis? To date, the available data are limited, and our study highlights the wide variability in treatment practices, ranging from monotherapy to triple antifungal therapy. This variability reflects the complexity of the disease, the intrinsic resistance of Fusarium species to available antifungal agents, and the lack of good data regarding the optimal approach,” says Vega.
Tragically, overall mortality in the patients with IF was 68%, with fusariosis directly implicated in 10 out of 15 deaths, with other attributed primary to relapsed leukemia. The findings reinforce that fusariosis remains a challenging threat in cancer care, exposing a concerning gap where prophylactic drugs fail and highlighting the need for larger, multi-center prospective studies to identify combination treatment strategies that can improve survival.
“We are currently taking a closer look at the cutaneous manifestations of fusarium among this patient population. As it is known, skin lesions are often one of the earliest visible signs of infection that lead to the diagnosis. By the time cutaneous lesions appear, are we already too late in the diagnosis of this disease? Is improvement of skin findings associated with better outcomes?” Vega adds. “Many questions remain unanswered, but we hope our work increases awareness among physicians caring for immunocompromised patients, promotes earlier recognition and diagnosis of fusariosis and highlights the urgent need for greater collaboration across centers to improve outcomes for patients with these devastating infections.”
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. David Fredricks and Steven Pergam contributed to this research.
The spotlighted research was supported by the Institute of Translational Health Sciences, National Institute of Allergy and Infectious Diseases of the National Institutes of Health and National Cancer Institute Cancer Center support.
Vega P, Bhattacharyya P, Lieberman JA, Kuczmarski TM, Yoke LH, So LM, Smith HZ, Lengermann R, Cohen S, Fredricks DN, Pergam SA. 2026. Fusariosis in Patients With Hematologic Malignancies in the Era of Antifungal Prophylaxis. Transpl Infect Dis. doi: 10.1111/tid.70203.
Science Spotlight writer Kelly Mitchell is a postdoctoral fellow in the Paddison Lab at Fred Hutch Cancer Center. She utilizes live cell reporters and CRISPR screening to study how glioblastoma cancer cells resist chemotherapy and radiation treatment. She obtained her PhD in cellular biology from Albert Einstein College of Medicine.