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Background: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making., Methods: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC., Results: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents., Conclusion: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs) and be well tolerated. This prospective, randomized, open-label, multicentre study compared the efficacy and safety of voriconazole (234 patients) versus itraconazole (255 patients) in alloHCT recipients. The primary composite endpoint, success of prophylaxis, incorporated ability to tolerate study drug for ≥ 100 d (with ≤ 14 d interruption) with survival to day 180 without proven/probable IFI. Success of prophylaxis was significantly higher with voriconazole than itraconazole (48·7% vs. 33·2%, P < 0·01); more voriconazole patients tolerated prophylaxis for 100 d (53·6% vs. 39·0%, P < 0·01; median total duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events were vomiting (16·6%), nausea (15·8%) and diarrhoea (10·4%) for itraconazole, and hepatotoxicity/liver function abnormality (12·9%) for voriconazole. More itraconazole patients received other systemic antifungals (41·9% vs. 29·9%, P < 0·01). There was no difference in incidence of proven/probable IFI (1·3% vs. 2·1%) or survival to day 180 (81·9% vs. 80·9%) for voriconazole and itraconazole respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis after alloHCT, based on differences in the primary composite endpoint. Voriconazole could be given for significantly longer durations, with less need for other systemic antifungals., (2011 Blackwell Publishing Ltd.)

Invasive fungal diseases (IFDs) have been widely studied in recent years, largely because of the increasing population at risk. Aspergillus and Candida species remain the most common causes of IFDs, but other fungi are emerging. The early and accurate diagnosis of IFD is critical to outcome and the optimisation of treatment. Rapid diagnostic methods and new antifungal therapies have advanced disease management in recent years. Strategies for the prevention and treatment of IFDs include prophylaxis, and empirical and pre-emptive therapy. Here, we review the available primary literature on the clinical and economic burden of IFDs in Europe from 2000 to early 2011, with a focus on the value and outcomes of different approaches. [ABSTRACT FROM AUTHOR]