The Case for Empiric Antifungal Therapy for Invasive Candidiasis in Preemies

April 05, 2012

By Megan Brooks

NEW YORK (Reuters Health) Apr 03 - Empiric therapy in extremely low birth weight (ELBW) infants with invasive Candida helps avoid death and neurodevelopmental impairment, according to retrospective data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.

"In infants at high risk of invasive Candida infections, clinicians should strongly consider using empiric antifungal therapy; do not wait for the blood culture results to be known to start therapy," senior investigator Dr. D. Brian Smith from Duke University Medical Center and Duke Clinical Research Institute told Reuters Health.

In a report online now in The Journal of Pediatrics, he and his colleagues note that Candida species are a leading cause of death in neonatal intensive care units. The incidence of candidemia in ELBW infants ranges from 2% to 20%. Blood culture -- the standard way to diagnose candidemia -- takes an average of two days to become positive and can yield false-negative results. Relying on blood culture results, therefore, can lead to underdiagnosis of Candida infection and delays in antifungal therapy, which could have fatal consequences in preemies.

When invasive Candida infection is suspected in adults with fever and neutropenia, empirical therapy (before blood culture results are available or in the face of a negative result) has been shown to improve outcomes. Yet, there are no randomized trials evaluating empiric therapy for infants at high risk of invasive Candida infections, Dr. Smith said, "and previous studies of empiric therapy were small."

His new paper reports outcomes of 136 infants with a birth weight of 1000 g or less who were cared for at Neonatal Research Network sites. All had a least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal agent on the day of, or the day before the first positive culture was drawn. Thirty-nine infants received empiric therapy (most often amphotericin B) and 97 did not.

The investigators report that 47 of the 136 infants died (35%) and the incidence of neurodevelopmental impairment (NDI) was 32% (23 of 73 infants). The rate of death or NDI at 18-22 months adjusted age was 60% (74 of 124 infants), which authors say is "consistent with data from previous studies of infants with Candida infection."

Of note, say the researchers, fewer infants who received empiric antifungal therapy died or developed NDI (19 of 38; 50%) compared with those who did not (55 of 86; 64%), yielding an odds ratio of 0.27.

The authors note in their report that the most recent guidelines from the Infectious Disease Society of America for the management of adult and pediatric patients with invasive and mucosal candidiasis do not address the issue of empiric therapy in infants.

"As NICUs are faced with caring for increasing numbers of extremely premature infants, guidelines for empiric antifungal therapy will be essential," they conclude.

For now, said Dr. Smith, "clinicians should add empiric antifungal therapy in the highest risk infants," that is, those who are extremely premature, have been exposed to broad spectrum antibiotics, or have thrombocytopenia.


J Pediatr 2012.


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