Tacke, D., Buchheidt, D., Karthaus, M., Krause, S.W., Maschmeyer, G., Neumann, S., . . . Cornely, O.A. (2014). Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Annals of Hematology, 93, 1449–1456.
DOI Link
Purpose & Patient Population
PURPOSE: To update key recommendations regarding the use of antifungal prophylaxis to incorporate data from recently published studies
TYPES OF PATIENTS ADDRESSED: Adult patients with hematologic malignancies; guidelines are further divided into recommendations for neutropenic patients (defined as < 500 cells/ml for more than seven days) excluding allogeneic hematopoietic stem cell transplant (HSCT); HSCT pre- and postengraftment and in the presence or absence of graft versus host disease (GvHD); and patients with other hematologic or oncologic diseases
Type of Resource/Evidence-Based Process
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Following the literature search, data were extracted and tabulated, then preliminary recommendations were proposed for discussion by a committee. Evidence tables were revised after e-mail discussion, then presented for final discussion at a guideline conference.
SEARCH STRATEGY: Not applicable
KEYWORDS: Invasive fungal infection, antifungal prophylaxis, itraconazole, fluconazole, posaconazole, amphotericin B, and liposomal
INCLUSION CRITERIA: Not applicable
EXCLUSION CRITERIA: Not applicable
Phase of Care and Clinical Applications
PHASE OF CARE: Multiple phases of care
Results Provided in the Reference
This update includes information from 14 clinical trials (eight randomized) involving 2,899 patients published since 2009. The quality of evidence and the strength of recommendations were guided by criteria from the Infectious Diseases Society of America and the United States Public Health Service grading systems and are presented in table format.
Guidelines & Recommendations
For neutropenic patients with acute myeloid leukemia or myelodysplastic syndrome (MDS) during remission-induction chemotherapy, the strongest recommendations were for posaconazole oral suspension (200 mg orally three times per day) or tablets (300 mg orally daily). Moderate evidence supported the same posaconazole dosing for consolidation therapy, very severe aplastic anemia, or the palliative treatment of MDS. Inhaled liposomal amphotericin B (12.5 mg biweekly) also is supported by moderate evidence. There is poor support for recommending caspofungin (50 mg IV daily), fluconazole (400 mg orally daily), itraconazole capsules (any dose), itraconazole oral solution (2.5–7.5 mg/kg daily), itraconazole (200 mg IV daily), liposomal amphotericin B (50 mg IV every 48 hours), and voriconazole (200 mg IV twice per day). The guidelines recommend against amphotericin B deoxycholate IV or inhaled.
In patients receiving pre-engraftment HSCT, fluconazole (400 mg orally daily), micafungin (50 mg IV daily), voriconazole (200 mg orally twice per day), and posaconazole suspension and tablets (dosed as above) have moderate evidence to support their use. Itraconazole (400 mg orally daily) had poor evidence supporting its recommendation.
Following engraftment, patients were further stratified into those with and without GVHD. If GVHD was present, posaconazole (same dosing as pre-engraftment) had good evidence to support the recommendation for its use. There was moderate evidence to avoid fluconazole in the presence of GVHD. In the absence of GVHD, oral fluconazole and posaconazole (all using the same dosing as for pre-engraftment) had poor evidence to support their recommendation. Itraconazole, voriconazole, and micafungin (all using the same dosing as for pre-engraftment) also had poor evidence to support their recommendation regardless of GVHD status.
In all other patients with malignancies, itraconazole (at any dose) had a poor recommendation. There was good evidence to support the avoidance of fluconazole (< 400 mg per day), amphotericin B deoxycholate, ketoconazole, miconazole, clotrimazole, nystatin, and oral amphotericin B (all at any dose).
Limitations
Only eight of the 14 studies considered were randomized, controlled trials.
Nursing Implications
Unlike previous versions, the newest guidelines provide separate recommendations for allogeneic HSCT in the pre- and postengraftment phases and in the presence or absence of GVHD. If GVHD is present, posaconazole is considered the drug of choice while fluconazole use is discouraged. Because the labeling of antifungal compounds can vary by country, the guidelines may not necessarily follow approved indications. They do, however, reflect published evidence.
