What are the treatment options for Fusarium fungal wound infection?

From the Guidelines

Fusarium wound infections require prompt medical attention with a combination of surgical debridement and antifungal therapy, with voriconazole as the first-line treatment at a loading dose of 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours, as recommended by the ESCMID and ECMM joint guidelines 1. Treatment typically involves voriconazole as first-line therapy, with transition to oral therapy at 200-300 mg twice daily once the patient improves. Alternatively, liposomal amphotericin B at 3-5 mg/kg/day IV may be used, especially in severe cases, as suggested by the practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America 1. Treatment duration typically ranges from 6-12 weeks depending on infection severity and immune status. Surgical debridement of infected tissue is crucial to remove necrotic material and reduce fungal burden. For immunocompromised patients, addressing underlying immune deficiencies is essential for successful treatment. Fusarium species are particularly concerning because they're often resistant to multiple antifungals and can cause invasive infections, especially in immunocompromised individuals. These molds typically enter through traumatic skin injuries, burns, or surgical wounds, producing characteristic red or necrotic lesions. Regular wound monitoring is necessary to assess treatment response, with follow-up cultures to confirm eradication of the infection. Some key points to consider in the management of Fusarium wound infections include:

• The importance of prompt medical attention and combination therapy with surgical debridement and antifungal agents
• The use of voriconazole as first-line therapy, with alternative options such as liposomal amphotericin B in severe cases
• The need for addressing underlying immune deficiencies in immunocompromised patients
• The importance of regular wound monitoring and follow-up cultures to assess treatment response and confirm eradication of the infection. The ESCMID and ECMM joint guidelines provide a comprehensive approach to the diagnosis and management of hyalohyphomycosis, including Fusarium species infections, and recommend voriconazole as the first-line treatment for these infections 1. Additionally, the practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America provide guidance on the treatment of various skin and soft tissue infections, including those caused by Fusarium species 1. Overall, the management of Fusarium wound infections requires a comprehensive approach that includes prompt medical attention, combination therapy with surgical debridement and antifungal agents, and addressing underlying immune deficiencies in immunocompromised patients.

From the FDA Drug Label

1. 4 Scedosporiosis and Fusariosis Voriconazole for injection is indicated for the treatment of serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani, in adults and pediatric patients (2 years of age and older) intolerant of, or refractory to, other therapy [see Clinical Studies (14.4) and Microbiology (12. 4)].

Voriconazole is indicated for the treatment of serious fungal infections caused by Fusarium spp., including Fusarium solani, in adults and pediatric patients (2 years of age and older) intolerant of, or refractory to, other therapy 2.

• The treatment should be initiated with a loading dose regimen of intravenous voriconazole on Day 1 followed by the recommended maintenance dose (RMD) regimen.
• Intravenous treatment should be continued for at least 7 days.
• Once the patient has clinically improved and can tolerate medication given by mouth, the oral tablet form or oral suspension form of voriconazole may be utilized.

From the Research

Characteristics of Fusarium Fungal Wound Infection

• Fusarium species are ubiquitous and can be found in soil, air, and on plants 3
• Fusarium infection is considered an emerging problem and should be suspected in immunocompromised patients experiencing systemic infection 4
• The skin can be an important and early clue to diagnosis since cutaneous lesions may be observed at an early stage of the disease 3

Diagnosis of Fusarium Infection

• Diagnosis of Fusarium infection may be made on histopathology, gram stain, mycology, blood culture, or serology 3
• Culture methods and microscopy are still routinely used in clinical laboratories to identify Fusarium spp, but more sophisticated methods such as serological assays and specific nested PCR assays can improve diagnosis 4
• Mass spectroscopy techniques can also provide accurate and consistent results 4

Treatment of Fusarium Infection

• High dose intravenous amphotericin B formulation is recommended as the first line of therapy in management of fusariosis in patients 4
• Voriconazole is also effective in treating fusariosis, and posaconazole is licensed as salvage therapy against invasive fusariosis 4, 5
• Adjunctive therapies such as surgical debridement of infected tissue, granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) infusions, or granulocyte transfusions are also tools for managing fusariosis 4
• Recovery of neutropenia is essential for patient survival, and treatment should include voriconazole or amphotericin B as first-line and posaconazole as salvage therapy 5

Antifungal Resistance

• Fusarium species have intrinsic resistance to most antifungal agents, resulting in high mortality rates in immunocompromised patients 5, 6
• In vitro resistance of clinical Fusarium species to amphotericin B and voriconazole has been observed, with clinical isolates being more resistant than reference isolates 7
• Species- and strain-specific differences in antifungal susceptibility exist within Fusarium, and susceptibility testing is important to improve the prognosis of these infections 7