Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014

Abstract

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Voriconazole for prophylaxis of invasive fungal infections after allogeneic hematopoietic stem cell transplantation

“…Several major international bodies have published recommendations for prophylaxis of IFIs in recipients of alloHSCT; a summary of selected guidelines and recommendations are presented in Table 1 [18,22,[37][38][39][40][41][42][43][44]. In general, fluconazole, itraconazole, and voriconazole are recommended for prophylaxis of IFI in recipients of alloHSCT who have no additional risk factors, with posaconazole recommended in patients with GVHD (although the level of supporting evidence varies between agents).…”

“…In general, fluconazole, itraconazole, and voriconazole are recommended for prophylaxis of IFI in recipients of alloHSCT who have no additional risk factors, with posaconazole recommended in patients with GVHD (although the level of supporting evidence varies between agents). In patients at high risk of IFI (please see previous description of IFI risk factors), primary prophylaxis with mold-active triazoles such as itraconazole, posaconazole, or voriconazole is typically recommended [18,22,37,38,45]. However, the local epidemiology of yeast/mold infections should also be taken into account when selecting appropriate prophylaxis [37].…”

“…Individual risk factors include: older age; use of broad-spectrum antibiotics (and the effect on gut microbiota); iron overload; use of central venous catheter; diabetes; prior IFI (or species colonization); and lower respiratory tract infection [17,18]. Additionally, patients receiving transplantation from a haploidentical donor have been shown to be at an elevated risk of IFI compared with HLA-matched siblings [19].…”

“…Itraconazole was subsequently shown to provide improved protection against aspergillosis [27] and IFIs [28] over 180 days after alloHSCT compared with fluconazole; however, tolerability issues are present, and absorption and bioavailability are unpredictable [27,28]. Newer-generation triazoles provide improved prophylactic options for IFIs in immunocompromised patients [18], with voriconazole demonstrating similar efficacy to fluconazole [29] and itraconazole [30] with improved tolerability compared with the latter; and with posaconazole therapy, which was non-inferior to fluconazole for prophylaxis against IFIs and IA events in patients with GVHD [31]. Use of prophylactic agents has resulted in improved patient outcomes over time [32,33].…”

Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology

“…We were pleased that a previous version of the Australasian paediatric antifungal guidelines (2007) was included [3], yet note that the comprehensive update of paediatric and adult Australian and New Zealand antifungal guidelines were omitted [4][5][6][7][8][9][10][11][12]. Published in December 2014, these expanded guidelines included manuscripts on prophylaxis, empiric and diagnostic-driven antifungal strategies, treatment of yeast, invasive mould and Pneumocystis jirovecii infection.…”