Mellinghoff, S.C., Panse, J., Alakel, N., Behre, G., Buchheidt, D., Christopeit, M., . . . Cornely, O.A. (2018). Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO). Annals of Hematology, 97, 197–207.

PURPOSE: To provide evidence-based guidelines for the prevention of fungal infections

TYPES OF PATIENTS ADDRESSED: Adults with hematologic malignancies, particularly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) receiving chemotherapy

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Guideline was prepared by German clinical experts in hematology, oncology, stem cell transplantation, and infectious diseases. This was done by a stepwise consensus process. Data was extracted and tabulated; the preliminary recommendations were discussed and sent to a committee of authors. Once revised by the authors, there was a discussion by email and telephone conference. If the vote was not unanimous, the majority vote was adopted. The final version was approved by the AGIHO plenary session. 

DATABASES USED: Not specifically described     

INCLUSION CRITERIA: Clinical trials regarding antifungal prophylaxis in patients with hematologic malignancies

PHASE OF CARE: Active anti-tumor treatment

There were seven clinical trials since the 2014 edition of the recommendations that were included in the 2017 update. These trials included a total of 1,227 patients.

Allogeneic stem cell transplantation recommendations were removed from this guideline and placed in a separate guideline.

Recommended antifungal prophylaxis in patients with neutropenia (neutrophils less than 500 cells/mcl for more than seven days (summary of table 2):

• Posaconazole is the level A recommendation (strongest level recommendation)
• Amphotericin B, liposomal, inhalation is a level B recommendations (moderate evidence to support a recommendation for use)
• IV amphotericin B and IV liposomal; caspofungin, fluconazole, itraconazole, intraconazole (IV), voriconazole, micafungin, and isavuconazole are all level C recommendations (poor evidence to support routine use)
• Amphotericin B deoxycholate is level D recommendation (supports a recommendation against use)

Recommendations for dosages (from table 3):

• Posaconazole, oral suspension – 200 mg three times per day
• Posaconazole, tablets – 300 mg daily (twice daily on day 1 only)
• Posaconazole, IV – 300 mg twice daily on day 1 only, then daily.
• Amphotericin B, liposomal, inhalation – 12.5 mg twice weekly
• Amphotericin B, liposomal, IV – 50 mg every 48 hours or 5 mg/kg twice weekly or 15 mg/kg single infusion (less supported)
• Caspofungin 50 mg daily (IV)
• Fluconazole – 400 mg daily
• Itraconazole, capsules – any dose
• Itraconazole, oral solution – 2.5–7.5 mg/kg per day or 200 mg
• Itraconazole, IV – 200 mg daily
• Voriconazole – 200 mg twice daily
• Amphotericin B deoxycholate – any dose
• Micafungin – 50 mg daily
• Isavuconazole – 200 mg daily (three times per day on days 1 and 2 only)

Recommendation for therapeutic drug monitoring (table 4):

• Voriconaozle – target level is 1-2 mg/L (level B)
• Posaconazole – target level is greater than 500 ng/mL (level C)

The guidelines are limited to a very specific group of patients–those with hematologic malignancies that will have a low neutrophil count (less than 500 cells/mcl for more than 7 days)

There is strong support for the use of antifungal prophylaxis, but the cost and effectiveness of the antifungal agent must be taken into account. Know the common fungal infectious causes in the geographical area and choose the right drug according to the specific fungus that is thought to be most prominent. Education about fungal infections as well as prevalence in this population is critical.