Introduction
Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. Several studies in the last years have reported on prevalence of invasive fungal infections (IFI), defined as involvement of lung, central nervous system, sinuses and bloodstream infections (BSI). We retrospectively reviewed data of hospitalized patients with hematological malignancies (HM) in which a diagnosis of fungemia was made between January 2011 and December 2015 at 33 adult and pediatric Italian Hematology Departments participating to the SEIFEM consortium. During the study period we recorded 215 fungal BSI among 215 patients with HM. Microbiological evaluation revealed that 8% of isolated strains was represented by molds, and among yeasts non-Candida strains accounted for 11% of all fungi. BSI was due to Candida spp in the residual 174 patients (81%), and Candida albicans represented 34% of all isolated strains in our population.
Among patients with Candida spp infection, 80 (46%) had a breakthrough infection during antifungal prophylaxis with fluconazole (45%) or a mold active drug (55%). Seventeen patients (9.7%) had no specific treatment for candidemia: 70.5% deceased before identification of isolate, while 29.5% survived despite absence of antifungal therapy. Treatment was an echinocandin in 52% of patients, followed by liposomal amphotericin B in 25% and fluconazole in 14%. Five patients (3%) were treated with various combination of two class of antifungal while in 6% other azoles were used.
Efficacy of treatment could be evaluated in 148 patients only: we assessed 48.7% of effective treatment in our series, even if 5 out of 72 patients still died of hematological progression or other complications. We assessed further 21% of efficacy among 55 patients which underwent second line antifungals. Overall mortality at 30 days was 38%, that lowered to 19% when considering only death related to candidemia. Factors associated with overall and attributable mortality in univariate analysis were ECOG >2, isolation of C.albicans, gastro-intestinal symptoms, multiorgan failure (MOF), septic shock, course of antifungal therapy, efficacy of first line and second line antifungal therapy. Use of steroids was significant only for overall mortality, while age >60 years and BSI from central venous catheter (CVC) were significant for attributable mortality only. Recovery of neutrophils count was found statistically significant for overall survival only in patients with acute myeloid leukemia.
Prophylaxis administration had no impact over survival, and none of antifungal drugs could demonstrate a superiority regarding overall and attributable mortality. Sex, age, type and phase of disease, occurrence of mucositis, diabetes, parenteral nutrition, previous surgical procedure or allogeneic transplant, dosage and duration of steroids, insertion and type of CVC, empirical antifungal therapy, fever, CVC related candidemia were not statistically significant in univariate analysis. In multivariate analysis ECOG >2 and efficacy of treatment retained their statistical significance for overall mortality, while ECOG >2, clinical signs of MOF and septic shock were statistically significant for attributable mortality. This retrospective multicentric study shows that epidemiology of fungal BSI is changing, and the efficacy of antifungal treatment is constantly improving both overall and attributable mortality in the last decades.