VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

The optimal management of invasive fungal infections (IFIs) in children requires prompt and precise diagnosis that enables timely implementation of appropriate antifungal therapy and decreased use of unnecessary toxic antifungals. Areas covered: Traditional approaches such as culture, microscopy and histopathology remain the gold standard but are often not sufficiently sensitive and specific. These limitations have led to the development of alternative non-invasive diagnostic methods that in most cases detect fungal components, such as antigens or nucleic acids. To date, galactomannan and 1,3 β-D-glucan assays are the most efficient non-culture methods for diagnosis and monitoring of antifungal therapy. New technologies from nano-sciences are applied, like T2Candida assay. However, these are not standardized or validated in children. Herein, we focus on IFI diagnosis emphasizing current perspectives, interpretation difficulties, and need for further evaluation in pediatrics. Expert commentary: The new diagnostic tools may enhance diagnostic capacity in combination with traditional methods.

Scedosporium and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. We herein assessed the ability of Scedosporium apiospermum ( SA ) and Fusarium solani species complex ( FSSC ) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB) and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT reduction assay. Planktonic cell and biofilm MIC50’s were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5-32 mg/L) with VRC (0.125-64 mg/L) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MIC50’s of D-AMB and L-AMB against SA isolates were 1 and 2 mg/L and against FSSC isolates were 0.5 and 1 mg/L, respectively. Biofilm MIC50’s of VRC against SA and FSSC were 32 mg/L and >256 mg/L, respectively. Synergistic effects were observed at 2-4 mg/L of L-AMB combined with 4-16 mg/L of VRC against SA biofilms (mean ΔE±standard error: 17% ± 3.7%). Antagonistic interactions were found at 0.5-4 mg/L of L-AMB combined with 0.125-16 mg/L of VRC against FSSC isolates with -28% ± 2%. D-AMB and L-AMB were more efficacious against SA and FSSC biofilms than VRC.

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Background Mould infections caused by Scedosporium apiospermum and Fusarium solani species complex (FSSC) biofilms are rising among immunocompromised and immunocompetent patients. Little is known about the immunomodulatory effects of antifungal agents against these moulds. We examined the effects of deoxycholate and liposomal amphotericin B (DAmB, LAmB) and voriconazole on antifungal activities and immune responses of neutrophils (PMNs) against mature biofilms compared with their planktonic counterparts. Methods Antifungal activity of human PMNs exposed to mature biofilms and planktonic cells for 24 h was determined at effector-to-target ratios of 2:1 and 5:1, alone or combined with DAmB, LAmB and voriconazole, assessed as fungal damage by XTT assay. Cytokine production was evaluated by multiplex ELISA, following PMN stimulation with biofilms in the presence/absence of each drug. Results All drugs showed additive or synergistic effects with PMNs against S. apiospermum at 0.03–32 mg/L. They showed antagonism primarily against FSSC at 0.06–64 mg/L. Increased IL-8 was produced by PMNs exposed to S. apiospermum biofilms plus DAmB or voriconazole compared with PMNs exposed to biofilms alone (P < 0.01). During combined exposure, IL-1β was increased, an effect only counteracted by increased levels of IL-10 caused by DAmB (P < 0.01). LAmB and voriconazole caused similar IL-10 levels with those released by biofilm-exposed PMNs. Conclusions The synergistic, additive or antagonistic effects of DAmB, LAmB or voriconazole on biofilm-exposed PMNs are organism-specific, with FSSC exhibiting greater resilience than S. apiospermum to antifungals. Biofilms of both moulds caused dampened immune responses. The drug-mediated immunomodulating effect on PMNs, evidenced by IL-1β, enhanced host protective functions.