What is the role of antifungal (anti-fungal) prophylaxis?

From the Guidelines

Antifungal prophylaxis is recommended for high-risk patients, such as those with profound, protracted neutropenia and grade III or IV mucositis, to prevent invasive fungal infections. For patients undergoing hematopoietic stem cell transplantation or with prolonged neutropenia due to chemotherapy, a mold-active triazole, such as posaconazole 300mg daily, is recommended where the risk of invasive aspergillosis is high 1. The choice of antifungal agent should be based on the likely pathogens, patient-specific factors, and potential drug interactions.

Key Considerations

• Antifungal prophylaxis should be considered in patients with a high risk of invasive candidiasis or invasive mold infection, such as those with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) during the neutropenic period associated with chemotherapy 1.
• A mold-active antifungal, such as posaconazole, should be considered in patients with late-stage post-allogeneic stem cell transplantation or graft-versus-host disease (GVHD) 1.
• Echinocandins, such as micafungin or caspofungin, are alternatives for patients with liver dysfunction or drug interactions 1.

Patient-Specific Factors

• The risk of invasive fungal infections should be assessed individually for each patient, taking into account factors such as the type and duration of immunosuppression, the presence of GVHD, and the use of corticosteroids or biological agents.
• Regular monitoring of liver function and drug levels is essential during antifungal prophylaxis to minimize the risk of adverse effects and ensure optimal efficacy.

Recent Guidelines

• The most recent guidelines recommend the use of systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation recipients, with a preference for an echinocandin or a mold-active azole 1.

From the FDA Drug Label

14.2 Prophylaxis of Aspergillusand CandidaInfections withNoxafil ® Oral Suspension Two randomized, controlled studies were conducted using posaconazole as prophylaxis for the prevention of invasive fungal infections (IFIs) among patients at high risk due to severely compromised immune systems.

1. 3 Prophylaxis of Candida Infections in Hematopoietic Stem Cell Transplant Recipients In a randomized, double-blind study, micafungin for injection (50 mg IV once daily) was compared to fluconazole (400 mg IV once daily) in 882 [adult (791) and pediatric (91)] patients undergoing an autologous or syngeneic (46%) or allogeneic (54%) stem cell transplant

Antifungal Prophylaxis is supported by the FDA drug label for:

• Posaconazole (PO): for the prevention of invasive fungal infections (IFIs) among patients at high risk due to severely compromised immune systems 2.
• Micafungin (IV): for the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients 3. Key points include:
• Posaconazole oral suspension was compared to fluconazole capsules in a randomized, double-blind trial for prophylaxis against invasive fungal infections in allogeneic hematopoietic stem cell transplant (HSCT) recipients with Graft versus Host Disease (GVHD) 2.
• Micafungin for injection was compared to fluconazole in a randomized, double-blind study for the prophylaxis of Candida infections in hematopoietic stem cell transplant recipients 3.

From the Research

Antifungal Prophylaxis

• Antifungal prophylaxis is crucial in preventing invasive fungal infections (IFIs) in patients with hematological malignancies, particularly those undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation 4.
• The use of antifungal prophylaxis has reduced the incidence of infections from yeasts, such as candidemia, although mortality rates remain high 4.
• Patients with acute myeloid leukemia (AML) are at high risk of developing IFIs, and antifungal prophylaxis is essential in reducing this risk 5, 6.

Risk Factors for Invasive Fungal Infections

• Neutropenia, intensive care unit (ICU) follow-up, and mechanical ventilation (MV) increase the risk of IFIs in patients with acute leukemia 7.
• Prolonged severe neutropenia and receipt of tacrolimus are associated with an increased risk of breakthrough IFIs in patients with AML 5.
• Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and those with other conditions of severe and prolonged immunosuppression are at high risk of developing IFIs 6.

Diagnosis and Treatment of Invasive Fungal Infections

• Early diagnosis of IFIs is critical in facilitating treatment success, and diagnostic tests such as blood cultures, galactomannan antigen, and diagnostic imaging should be rigorously enforced in patients at risk 6, 8.
• The choice of antifungal therapy requires careful consideration of several factors, including risk stratification, local fungal epidemiologic patterns, and concomitant comorbidities 6, 8.
• Prophylaxis with posaconazole is recommended for allogeneic HSCT recipients, patients receiving induction chemotherapy for AML or myelodysplastic syndrome (MDS), and those undergoing immunosuppressive therapy for graft-versus-host disease after allogeneic HSCT 6.