Summary of ‘Antifungal therapy in infants and children with proven, probable or suspected invasive fungal infections’

Authors


Abstract

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: 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 of Systematic Reviews 2010, Issue 2. Art. No.: CD006343. DOI: 10.1002/14651858.CD006343.pub2. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Objectives

  • This review aims to investigate different antifungal therapies in children with proven, probable or suspected invasive fungal infections (IFI).

Relevance

  • Most children who develop fungal infections have received chemotherapy for a malignancy or have undergone a haematopoietic stem cell or solid organ transplant. The incidence of IFI in these groups is between 5% and 25%.

  • Early and aggressive treatment of suspected infections with empiric antifungal therapy is common.

  • Conventional amphotericin B deoxycholate is a broad spectrum antifungal agent that has been the usual treatment in the past for most IFI. Its use is complicated by nephrotoxicity and infusion-related reactions. More recently, other agents such as lipid formulations of amphotericin B, triazole derivatives and echinocandins have increased treatment options.

Participants

  • This review included seven trials with a total of 629 participants.

Comparison

  • This review looked at trials that compared antifungal agents to other antifungal agents or combination of agents, no treatment or an inactive placebo.

Results

  • Four trials compared lipid amphotericin B with amphotericin B deoxycholate in suspected IFI. Two trials compared micafungin with liposomal amphotericin B—one in proven invasive candidiasis and one in suspected IFI. The seventh trial compared flucanozole to itraconozole in proven invasive candidiasis.

  • Quality of the trials was moderate to high, with one being reported only in abstract form.

  • No difference was found for the primary outcomes of all-cause mortality, infection-related mortality, and resolution of infection (if the child had a proven IFI) in any trial or in pooled data but these outcomes were not reported for all seven trials.

  • With regard to secondary outcomes, treatment with a lipid preparation of amphotericin B (vs conventional amphotericin B) significantly decreased nephrotoxicity (RR: 0.43, 95% CI: 0.21, 0.90). Also in comparison with conventional amphotericin B, liposomal amphotericin decreased infusion-related chills (RR: 0.37; 95% CI: 0.21, 0.64) but amphotericin B colloidal dispersion (another lipid amphotericin preparation) increased infusion-related chills (RR 1.76, 95% CI 1.09 to 2.85, p = 0.02) with each comparison being based on only one study. There was no significant difference in any other secondary outcomes including partial resolution of proven IFI, resolution of fever, progression of disease, breakthrough fungal infections, or other adverse events. Again, reporting was incomplete for all outcomes.

Implications

  • Recognizing the paucity of data, it is reasonable to recommend a lipid preparation of amphotericin B over conventional amphotericin B in children with suspected or proven IFI to minimize nephrotoxicity if cost permits.

  • Echinocandins may be considered as an alternative to amphotericin B preparations as efficacy and safety appear to be comparable. Again, data is limited.

  • There are no pediatric RCTs with newer triazoles (voriconazole and posaconazole).

How Recent is the Evidence

  • Databases were searched up to September 2008.

Research Gaps

  • Further epidemiological studies clarifying differences between neonates, children and adults with IFI are needed.

  • Further randomized controlled antifungal trials enrolling children are required.

Ancillary