Question

• Does antifungal prophylaxis decrease the rates of fungal infections and improve outcomes in very/extremely low birth weight (VLBW/ELBW) neonates?

Clinical Bottom Lines

1. Fluconazole decreased the rates of all grades of colonization in all sites in VLBW neonates.¹  Colonization is the single most important factor leading to systemic infection.
2. Prophylactic fluconazole significantly decreased the rate of progression from colonization to systemic infection.
3. Prophylactic fluconazole decreased the incidence of presumed and proven fungal infections in the patient population studied.
4. Mortality was found to be lower in colonized neonates, though not lower when the population was taken as a whole.

Summary of Key Evidence

1. Incidence of systemic fungal infection was significantly lower in the treatment group (p<.0001).¹
2. Number needed to treat to prevent one fungal infection was 14.
3. Number needed to treat to prevent 1 death from a fungal infection was 100.
4. Overall mortality was similar in both groups.
5. The overall incidence of fluconazole-resistant species did not increase.  There was also no increase in the resistance rates of Candida albicans to fluconazole.

Additional Comments

1. Candidal sepsis is the third leading cause of sepsis in VLBW neonates.
2. A survey performed by the CDC has noted that currently about 1/3 of perinatologists perform some kind of fungal prophylaxis.²
3. The type of study that was performed (retrospective cohort study) is limited in its ability to be generalized to other patient populations.  Double-blinded placebo-controlled trials need to be performed.
4. The only double-blinded and placebo-controlled trial to date utilizing fungal prophylaxis has noted benefit in the patients studied (characteristics chiefly involved central lines and intubation).

Citation

1. Manzoni P, Arisio R, Mostert M, et al.  Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study. Pediatrics 2006;117:e22-32.
2. Burwell LA, Kaufman D, Blakely J, Stoll BJ, Fridkin SK Antifungal prophylaxis to prevent neonatal candidiasis: A survey of perinatal physician practices. Pediatrics 2006;118:e1019-26.

CAT Author: Dave Selewski, MD

CAT Appraisers: Cynthia Chi, MD

Date appraised: June 13, 2007