gms | German Medical Science

Background: Risk for invasive fungal infections (IFIs) is high in children undergoing antineoplastic chemotherapy or hematopoietic stem cell transplant (HSCT). Despite timely diagnosis and appropriate antifungal therapy, clinical outcome may be poor and prolonged antifungal treatment is needed.

Methods: This multi-center, retrospective study, analyzed characteristics, treatment modalities and outcome of 133 proven-probable invasive fungal diseases (IFD) occurred between January 2006 and December 2012 in 128 children and adolescents.

Results: Among the 133 cases of IFDs reported during the study period, 79 (59%) were classified as probable and 54 (41%) as proven. According to the time of diagnosis of IFD, 75 episodes (56%) occurred after HSCT, 19 after relapse of disease and 39 after primary diagnosis, usually during remission-induction chemotherapy. Severe neutropenia was present in 75% of episodes. Thirty-two cases of Candida spp (mostly Candida non-albicans), 99 moulds and 2 other species were detected. In the first 2 weeks from diagnosis of IFD, monotherapy and combined antifungal therapy were used in 59% and 36% of episodes, respectively; 5% of episodes were not treated for several reasons. Among the 78 episodes treated with mono-therapy during the first 14 days, the treatment was switched to combination in 6% of cases, remained unvaried in 81%, was withdrawn in 13%. The median duration of antifungal therapy was longer for the episodes treated with combination therapy (69 days, range 6-90) compared to episodes treated with mono-therapy (48 days, range 3-90), p ns. At 90-days from diagnosis of IFI, in 49 episodes, antifungal therapy was on going.

A favorable response (complete or partial remission) to antifungal therapy at 90 days was obtained in 81 episodes (89%). Overall survival (OS) probability at 90 days was 68% (59-76). According to the timing of diagnosis of IFD, 90-day OS was 62% after HSCT, 74% after relapse, and 79% after diagnosis of underlying disease, p ns. Absence of severe neutropenia at diagnosis of IFD (p=0.04) and absence of antifungal prophylaxis (p=0.03) were significantly associated to a better overall survival in univariate analysis.

Conclusions: In the last decade, we observed an improvement of OS compared to previous reported results. In absence of precise pediatric therapeutic guidelines, we recorded that the use of combination therapy, as off-label therapeutic approach, was present in almost half episodes. Prospective studies are needed to assess the cost/effectiveness ratio of combination versus mono-therapy in paediatric IFI.