When and how to treat
invasive fungal infections (IFIs) is discussed in this review, with a focus on the two most prevalent non-endemic IFIs, namely invasive
aspergillosis and
invasive candidiasis. Early treatment initiation in patients with IFIs has a profound impact on mortality rates, but reliable diagnostic measures are lacking. This situation has led to the parallel use of different treatment strategies, e.g. prophylaxis, empirical and pre-emptive treatment, as well as targeted treatment in response to a definite diagnosis of IFI. Identifying high-risk patients is the first step in reducing IFI-related mortality. Patients at risk of invasive
aspergillosis comprise (i) those with acute myelogenous leukaemia (AML) or
myelodysplastic syndrome (MDS) during
remission induction chemotherapy; (ii) patients undergoing allogeneic haematopoietic
stem cell transplantation (HSCT); (iii) recipients of solid organ transplants; and (iv) those with other conditions of severe and prolonged immunosuppression. Patients at high risk of
invasive candidiasis are less well defined. Risk factors are diverse and include haematological
malignancy,
neutropenia, age <1 month or >65 years, and recent abdominal surgery. The individual risk further depends on the presence of a variety of other risk factors, including
central venous catheters, use of broad spectrum antibacterials, prolonged intensive care unit (ICU) stay,
total parenteral nutrition, mucosal Candida spp. colonization and
renal failure.Extensive research has been conducted to facilitate the best possible treatment strategies for these severe
infections. Optimal timing and choice of
antifungal agents largely remain a matter of controversy. After having reviewed the major clinical trials, we conclude that comparisons between different treatment strategies cannot be made, neither at present nor in the near future. The complexity of the clinical problem leads to an eclectic treatment approach to reduce morbidity and mortality from IFIs without compromising tolerability. We recommend prophylaxis with
posaconazole for allogeneic HSCT recipients, patients receiving
induction chemotherapy for AML or MDS, and those undergoing immunosuppressive therapy for
graft-versus-host disease after allogeneic HSCT. For the empirical treatment of persistently
febrile neutropenia,
caspofungin is our first- and
liposomal amphotericin B deoxycholate (LAmB) our second-line choice. Once a diagnosis of invasive
aspergillosis has been established,
voriconazole should be the preferred treatment option, with LAmB being an alternative.
Fluconazole prophylaxis for
invasive candidiasis should remain restricted to high-risk ICU patients. Once a diagnosis has been established, the
drug of choice for adequate treatment depends largely on neutrophil count and haemodynamic stability. In non-neutropenic patients, an
echinocandin should be considered the first-line treatment option, while patients with susceptible Candida spp. may be switched to
fluconazole. In neutropenic patients,
caspofungin or
micafungin might be preferred to
anidulafungin as first-line treatment. LAmB is a second-line treatment option in both settings.Early diagnosis of IFIs is imperative to facilitate treatment success. In all patients at risk for IFIs, blood cultures,
galactomannan antigen and diagnostic imaging should be rigorously enforced.