Treatment of Fusarium Infection of the Central Nervous System: A Review of Past Cases to Guide Therapy for the Ongoing 2023 Outbreak in the United States and Mexico

Abstract

Introduction Fusariosis of the central nervous system (CNS) is extremely uncommon. Treatment and outcome data from previously published cases may provide some guidance in light of the ongoing fungal meningitis outbreak in 2023 involving Fusarium spp. in the United States and Mexico. Methods We reviewed the published literature describing cases of invasive fusariosis of the (CNS) that included data on patient demographic characteristics, treatment, and outcome. Results Twenty-six cases met inclusion criteria. The mean age was 36 years, 55% involved females, 60% had underlying hematologic malignancy, and another 16% were on immunosuppressants. The majority of infections were from Fusarium solani species complex. Overall 72% of patients died. The majority received monotherapy with amphotericin B, although some received voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole with or without adjuvant surgery. Among the survivors, 3 received amphotericin B monotherapy, 2 voriconazole monotherapy, 1 combination therapy of both, and one surgery only. Conclusion The overall mortality rate in published cases of fusariosis of the CNS was high, although—unlike during the current outbreak—the preponderance of patients were severely immunocompromised. While historically the majority were treated with amphotericin B monotherapy, some recent patients were treated with voriconazole monotherapy or combination therapy with amphotericin B plus voriconazole. Current guidelines recommend monotherapy with voriconazole or lipid formulations of amphotericin B or combination of both for the treatment of invasive fusariosis, which is in line with the findings from our literature review and should be considered during the ongoing 2023 outbreak.

Social determinants of health as drivers of fungal disease

“…Increased risk for candidemia has been associated with poor health care infrastructure and access in lower income countries. 126 Overcrowded intensive care units, insufficient air conditioning/ventilation systems, and lack of efficient infection control services predispose individuals from lower income countries to a greater risk for hospital and ICU outbreaks of IFIs, as recently shown for COVID-19-associated pulmonary aspergillosis, CAM, and CNS fusariosis outbreaks in Mexico, 123 , 127 , 128 as well as invasive Candida infections caused by fluconazole resistant C. parapsilosis 129 and C. auris . 130 Cryptococcosis is associated with advanced HIV infection as well as other medical comorbidities such as diabetes mellitus, corticosteroid use, and malignancy.…”

Advanced genetic techniques in fungal pathogen research

“…However, with global warming, fungi are adapting to higher temperatures, allowing them to survive and thrive in warm-blooded hosts. Recent outbreaks of emerging fungal pathogens, such as Exserohilum rostratum ( 11 ), Fusarium solani ( 12 ), and C. auris ( 13 ), highlight the inherent pathogenic potential of the fungal kingdom that can result in unexpected, growing fungal diseases worldwide. Moreover, many common pathogenic species are now becoming resistant to the limited number of treatments available ( 14 ).…”

Editorial: Emerging fungal pathogens: perspectives

“…In this context, despite the publication of the WHO FPPL, classically opportunistic fungi have been reported as agents of infections in immunocompetent patients. Recently, articles were published describing Fusarium solani as the causal agent of an outbreak of meningitis in Mexico and USA, both in immunosuppressed and immunocompetent patients ( Hoenigl et al., 2023 ; García-Rodríguez et al., 2024 ). In 2023, our group also published a case report of meningoencephalitis caused by Penicillium chrysogenum , a fungus widely distributed in nature, which, like C. auris , present in the high-priority group, acquired the ability to adapt to temperatures and cause diseases in healthy hosts ( de Oliveira et al., 2023 ).…”