Antifungal Therapy in Infants and Children with Invasive Fungal Infections

A Cochrane review [Abstract] 1 included 7 studies with a total of 629 children with prolonged fever and neutropenia (suspected fungal infection) and candidaemia or invasive candidiasis (proven fungal infection). Four studies compared a lipid preparation of amphotericin B with conventional amphotericin B (n=395), 1 study compared an echinocandin with a lipid preparation of amphotericin B (n=82) in suspected infection; 1 study compared an echinocandin with a lipid preparation of amphotericin B in children with candidaemia or invasive candidiasis (n=109) and 1 study compared different azole antifungals in children with candidaemia (n=43). No difference in all-cause mortality and other primary endpoints (mortality related to fungal infection or complete resolution of Fungal Infections) were observed. No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia.

When lipid preparations and conventional amphotericin B were compared in children with prolonged fever and neutropenia, nephrotoxicity was less frequently observed with a lipid preparation (RR 0.43, 95% CI 0.21 to 0.90, statistical heterogeneity I² =59%). The number of children needing to receive a lipid preparation of amphotericin B to avoid one child developing nephrotoxicity was 6 (95% CI 4 to 12). Children receiving liposomal amphotericin B were less likely to develop infusion-related reactions compared with conventional amphotericin B (chills: RR 0.37, 95% CI 0.21 to 0.64). Children receiving a colloidal dispersion were more likely to develop such reactions than with liposomal amphotericin B (chills: RR 1.76, 95% CI 1.09 to 2.85). The rate of other clinically significant adverse reactions attributed to the antifungal agent (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy; hypokalaemia and hepatotoxicity) were not significantly different. When echinocandins and lipid preparations were compared, the rate of clinically significant adverse reactions (total reactions; total reactions leading to treatment discontinuation, dose reduction or change in therapy) were not significantly different.

Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies).

References

• Blyth CC, Hale K, Palasanthiran P, O'Brien T, Bennett MH. Antifungal therapy in infants and children with proven, probable or suspected invasive Fungal Infections. Cochrane Database Syst Rev 2010;(2):CD006343. [PubMed]