Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies: a systematic review

J Antimicrob Chemother. 2014 Jan;69(1):1-11. doi: 10.1093/jac/dkt329. Epub 2013 Aug 23.


Objectives: Patients receiving therapy for haematological malignancies have a higher risk of invasive fungal infections (IFIs). Antifungal prophylaxis is an effective strategy against IFIs, but relative effectiveness estimates across agents are inconclusive. A mixed treatment comparison (MTC) was conducted to estimate the relative effectiveness of all agents for a number of outcomes of interest.

Methods: A systematic review was performed to collect evidence from randomized controlled trials (RCTs) on the risk of IFIs and on mortality after antifungal prophylaxis. The agents analysed were no prophylaxis/placebo, fluconazole, itraconazole, micafungin, caspofungin, liposomal amphotericin B and posaconazole. Meta-analyses and MTCs were used to synthesize the evidence. The primary outcome was the risk of proven or probable IFI. Secondary outcomes were risk of candidiasis/aspergillosis, risk of IFI mortality and risk of all-cause mortality.

Results: Antifungal prophylaxis was more effective than no prophylaxis/placebo in reducing IFI risk. The IFI risk after voriconazole or posaconazole was lower than after fluconazole [relative risk (RR) 0.38, 95% CI 0.14-0.83 and RR 0.34, 95% CI 0.14-0.83] or itraconazole tablets (RR 0.22 95% CI 0.06-0.72 and RR 0.20 95% CI 0.05-0.72). Posaconazole was also found to be more effective than no prophylaxis/placebo in reducing all-cause mortality (RR 0.56, 95% CI 0.30-0.98). Posaconazole had the highest probability of being the most effective agent in reducing IFI risk and all-cause mortality.

Conclusions: IFI prophylaxis has a positive effect on IFI risk reduction. However, its effect on all-cause mortality is not as pronounced. The analysis has additionally pinpointed posaconazole as potentially the most effective IFI prophylaxis in neutropenic patients.

Keywords: IFIs; antifungals; evidence synthesis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Chemoprevention / methods*
  • Hematologic Neoplasms / complications*
  • Hematologic Neoplasms / therapy
  • Humans
  • Mycoses / drug therapy*
  • Mycoses / epidemiology
  • Mycoses / mortality
  • Mycoses / prevention & control*
  • Neutropenia / chemically induced
  • Neutropenia / complications*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Survival Analysis


  • Antifungal Agents