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

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

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  • 1Toronto Health Economics and Technology Assessment (THETA) Collaborative, University of Toronto, Toronto, Ontario, Canada.



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.


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.


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.


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.


IFIs; antifungals; evidence synthesis

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