Evidence-based review of antifungal prophylaxis in neutropenic patients with haematological malignancies.
BACKGROUND
There is still no consensus on the efficacy of antifungal prophylaxis in neutropenic patients after more than 50 clinical trials.


METHODS
This review evaluates the current evidence from all available meta-analyses of the use of intravenous amphotericin B, fluconazole and itraconazole for this indication.


RESULTS
Four systematic reviews with meta-analysis and one evidence-based review without meta-analysis were evaluated. Efficacy of fluconazole has been shown on short-term follow-up after allogeneic stem cell transplantation but only itraconazole was effective in neutropenic patients with haematological malignancies for prolonged prophylaxis after allogeneic stem cell transplantation. Direct comparison between fluconazole and itraconazole for this indication shows the superiority of itraconazole which was the only drug able to prevent invasive Aspergillus infections in our previously published meta-analysis of 13 trials and 3597 patients. Efficacy of itraconazole correlates closely with its dose; an effect was seen only in clinical trials using at least 400 mg/day oral solution or 200 mg/day intravenous solution. With this dose, invasive fungal infections were reduced by 53% and mortality from invasive fungal infections was reduced by 47% (P<0.05). Toxicity of itraconazole is rare and usually not severe and drug interactions are easily manageable.


CONCLUSIONS
Itraconazole is recommended for antifungal prophylaxis in high-risk neutropenic patients with haematological malignancies or for prolonged prophylaxis after allogeneic stem cell transplantation based on unambiguous evidence of efficacy and low toxicity from clinical trials and systematic reviews.
Glasmacher
Axel
A
Department of Internal Medicine I, University of Bonn, 53105 Bonn, Germany. glasmacher@uni-bonn.de
Prentice
Archibald Grant
AG
D000666:Amphotericin B / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015725:Fluconazole / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009181:Mycoses / Q000517:prevention & control*; D009503:Neutropenia / Q000150:complications*; D033581:Stem Cell Transplantation
D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B; D015725:Fluconazole