Antifungal treatment strategies in high risk patients

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Abstract
We discuss different strategies for the treatment of invasive fungal infections (IFI) in high risk patients with a focus on patients experiencing profound and prolonged neutropenia, comprising those with acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) during remission induction chemotherapy and on patients undergoing allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, invasive aspergillosis (IA) is the most frequently observed form of IFI, as opposed to high risk intensive care unit (ICU) patients in whom an increased incidence of invasive candidiasis (IC) can be observed. In both groups, initiation of early treatment has a profound impact on mortality rates, but adequate diagnostic tools are lacking. These circumstances have led to the parallel use of different treatment strategies, e.g. prophylaxis, empiric, pre-emptive and targeted treatment of IFI. The optimum treatment strategies for these severe infections are a matter of extensive research and discussion. A review of major clinical trials on the issue reveals that comparisons between different treatment strategies cannot be made. Considering the complexity of the issue, we advocate an eclectic treatment approach that reduces morbidity and mortality from IFI without compromising tolerability. In allogeneic HSCT recipients, patients receiving induction chemotherapy for AML or MDS and those under immunosuppressive medication for graft vs. host disease after allogeneic HSCT, we recommend prophylaxis with posaconazole. For empiric treatment of persistently febrile neutropenic patients, we opt for caspofungin as first and liposomal amphotericin B deoxycholate (L-AmB) as second line choice. If the diagnosis of IA can be established, voriconazole should be favoured over the alternative, liposomal amphotericin B (L-AmB). While high risk ICU patients benefit from fluconazole prophylaxis for IC, the choice of an optimal agent for targeted therapy depends largely on the neutrophil count. In non-neutropenic patients, we recommend an echinocandin as the first line treatment option. Patients with susceptible Candida spp. may be switched to fluconazole. Caspofungin or micafungin might be preferred to anidulafungin in the neutropenic patient. L-AmB is a valuable second line treatment option for both groups of patients.