What is the best intravenous (IV) antifungal treatment for invasive fungal sinusitis?

From the Guidelines

The best intravenous antifungal treatment for invasive fungal sinusitis is typically liposomal amphotericin B at a dose of 5-10 mg/kg/day, as recommended by the most recent guidelines 1. This should be initiated immediately upon diagnosis or strong suspicion of invasive fungal sinusitis, as this condition is rapidly progressive and potentially fatal. The treatment duration is generally 4-6 weeks, depending on clinical response. For patients with mucormycosis, higher doses of liposomal amphotericin B (10 mg/kg/day) are recommended. In cases of Aspergillus infection, voriconazole may be used as an alternative, with a loading dose of 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours, as suggested by the Infectious Diseases Society of America guidelines 1. Renal function should be monitored closely during amphotericin B therapy due to its nephrotoxicity. Surgical debridement is an essential adjunct to antifungal therapy, as medications alone are often insufficient. After the initial IV therapy, patients typically transition to oral antifungals (such as posaconazole or voriconazole) for an extended period of 3-6 months. The aggressive approach with high-dose antifungals is justified by the poor tissue penetration of these medications into necrotic tissue and the angioinvasive nature of these fungi, which causes thrombosis and further limits drug delivery to infected areas. It's worth noting that the European position paper on rhinosinusitis and nasal polyps 2020 also supports the use of voriconazole in the setting of Aspergillus species 1. However, the most recent and highest quality study, which is the 2016 update by the Infectious Diseases Society of America, should be prioritized 1.

Some key points to consider when treating invasive fungal sinusitis include:

• The importance of prompt initiation of antifungal therapy
• The need for surgical debridement as an adjunct to medical therapy
• The potential for nephrotoxicity with amphotericin B therapy
• The option to use voriconazole as an alternative in cases of Aspergillus infection
• The transition to oral antifungals after initial IV therapy
• The need for close monitoring of renal function and adjustment of dosages as necessary.

Overall, the treatment of invasive fungal sinusitis requires a comprehensive approach that includes both medical and surgical interventions, and should be guided by the most recent and highest quality evidence available 1.

From the FDA Drug Label

In a clinical study of IA, the median duration of intravenous voriconazole therapy was 10 days (range 2 to 85 days).

Infection Loading dose Maintenance Dose Intravenous infusion Intravenous infusion Invasive Aspergillosis 9 mg/kg every 12 hours for the first 24 hours 8 mg/kg every 12 hours after the first 24 hours

Initiate therapy with an intravenous infusion regimen. Consider an oral regimen only after there is a significant clinical improvement.

The best intravenous antifungal treatment for invasive fungal sinusitis is not explicitly stated in the provided drug label. However, Invasive Aspergillosis is mentioned, which can be related to invasive fungal sinusitis.

• The recommended dosing regimen for Invasive Aspergillosis is:
  • Loading dose: 9 mg/kg every 12 hours for the first 24 hours
  • Maintenance dose: 8 mg/kg every 12 hours after the first 24 hours 2

From the Research

Treatment Options for Invasive Fungal Sinusitis

• The best intravenous antifungal treatment for invasive fungal sinusitis is a topic of ongoing research, with various studies suggesting different treatment options.
• Voriconazole has been shown to be effective in treating invasive fungal sinusitis, with studies indicating its potential as a new standard treatment 3, 4.
• Liposomal amphotericin B is also considered an effective alternative drug for adjuvant medical treatment, particularly in cases where conventional amphotericin B is not tolerated 5, 6.
• Itraconazole and amphotericin B have been found to be equally efficacious in the management of invasive fungal sinusitis, although itraconazole has fewer side effects compared to amphotericin B 7.

Key Considerations

• The choice of antifungal treatment may depend on various factors, including the type of fungus, the extent of the disease, and the patient's immune status.
• Surgery is often necessary to remove necrotic tissue and obtain diagnostic samples, and reversal of immunosuppression is crucial in the management of invasive fungal sinusitis 6.
• Early diagnosis and aggressive treatment are essential to improve outcomes, as mortality rates for invasive fungal sinusitis remain high 6.