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Invasive Fusariosis: A Retrospective Case Series Evaluating In Vitro Minimum Inhibitory Concentrations and Clinical
Victor Kovac1,2,3,4, Sarah P Hammond2,4,5, Nicolas C Issa1,2,3
1Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Abstract:
Invasive fusariosis (IF) is a rare but aggressive infection seen in immunocompromised patients that often exhibits elevated minimum inhibitory concentrations (MICs) to antifungal drugs, making the optimal therapeutic remains unknown. We identified all cases of IF between January 2015 and April 2024 and collected patient characteristics, including clinical presentation, therapy, and 12-week outcomes, as well as organism species identification and susceptibility testing. Twenty-one patients were diagnosed with either proven (n = 14) or probable (n = 7) IF. The mean age was 60 years and 71% were male. Hosts had hematologic disorders in 71% of which 80% had acute leukemia. Seventy-three percent were neutropenic at the time of IF diagnosis and 40% had received allogeneic stem cell transplantation. Infections were localized in 57% and disseminated in 43%. Skin was the most common site of involvement (67%), followed by pulmonary (42%) and sinus (21%). The most common species was Fusarium solani complex (38%). Susceptibility testing was performed on 81% of isolates. MICs were ≥4 µg/mL for mold-active triazoles in 94% and ≥1 µg/mL for terbinafine in 65%. The most common definitive regimens were a triazole plus terbinafine (62%) and triazole monotherapy (19%). Surgical debridement was performed in 52%. Seventy-six percent of patients survived to 12 weeks. Fifty-seven percent achieved complete responses, 29% partial responses, and 14% failed to respond to therapy at 12 weeks. Mortality in patients with IF is high. Despite elevated MICs, clinical responses to triazole antifungals with or without the addition of terbinafine are observed.
Insights
Invasive fusariosis (IF) is a serious fungal infection in immunocompromised patients. Despite high antifungal drug resistance, combination therapy with triazoles and terbinafine shows promising clinical responses and survival.
Area of Science:
- Mycology
- Infectious Diseases
- Clinical Medicine
Background:
- Invasive fusariosis (IF) is a rare, aggressive fungal infection primarily affecting immunocompromised individuals.
- Optimal treatment for IF remains challenging due to elevated antifungal drug minimum inhibitory concentrations (MICs).
Purpose of the Study:
- To analyze patient characteristics, treatment strategies, and outcomes for invasive fusariosis.
- To evaluate the efficacy of antifungal therapies in patients with IF, considering organism susceptibility.
Main Methods:
- Retrospective analysis of 21 proven or probable IF cases (January 2015 - April 2024).
- Collection of data on patient demographics, clinical presentation, antifungal susceptibility testing, therapeutic regimens, and 12-week outcomes.
- Identification of causative *Fusarium* species.
Main Results:
- The study included 21 patients (mean age 60 years, 71% male), predominantly with hematologic disorders (71%) and neutropenia (73%).
- *Fusarium solani* complex was the most common species (38%). High MICs were observed for triazoles (94%) and terbinafine (65%).
- Combination therapy (triazole + terbinafine) was used in 62% of patients, with a 76% 12-week survival rate and 57% complete response.
Conclusions:
- Invasive fusariosis carries a high mortality rate, particularly in patients with hematologic malignancies.
- Despite elevated MICs, combination antifungal therapy including triazoles and terbinafine demonstrates clinical efficacy and improves survival in IF.
- Early diagnosis, species identification, susceptibility testing, and aggressive management including surgical debridement are crucial for improving outcomes.
