MIAMI — Antifungal prophylaxis for very-low-birth-weight infants could decrease overall incidence of invasive infections and mortality, considerations that may outweigh valid concerns about emerging resistance, according to a poster presentation at a meeting on fungal infections sponsored by Imedex.
“We were seeing a lot of cases of invasive candidiasis in newborns,” Jaime G. Deville, M.D., said in an interview. So he and his associate performed a retrospective cohort study of all neonates at University of California Medical Center in Los Angeles from 1998 to 2002 with proven mycotic disease.
The impetus for the study was a patient with a particularly severe infection. The premature infant had an extremely low birth weight, approximately 650 g and was admitted to the neonatal intensive care unit (NICU). After receiving “all kinds of antibiotics” for sepsis over 2 months, he developed a heart valve infection. Physicians discovered a mass approximately one-fourth the size of his heart, Dr. Deville said. “At the same time, he started to grow Candida albicans.” Surgeons removed the mass, and the patient survived.
Opportunistic infections in the NICU are becoming increasingly common. They are associated with high mortality, prolonged hospital stays, and increased costs, according to Dr. Deville, a pediatrician specializing in infectious disease at the UCLA Medical Center.
The researchers assessed changes in invasive candidiasis incidence, fungal species, risk factors, and possible ways to intervene.
“To be honest, I was very surprised about the very high incidence in very-low-birth-weight infants,” Dr. Deville said in an interview. In this population, incidence of invasive fungal infections was 23% in 1998, 18% in 1999, 57% in 2000, 59% in 2001, and 50% in 2002. The incidence dropped in 2002 because “there was more awareness by the end of the 5-year period.”
Reports in the literature state a lower incidence of invasive fungal infections in newborns, perhaps because these studies are compiled from large pediatric databases, Dr. Deville said. “We think the incidence of invasive fungal infections is much larger than it appears in published papers.”
UCLA is a large tertiary-care center and “our population is selected toward the very sick.” For example, of the 1,686 infants admitted to the NICU during the study, 52% had a primary diagnosis of prematurity, 26% had congenital heart disease, 12% had chromosomal abnormalities, and 10% had noncardiac major malformations.
Overall, mortality from invasive fungal infections in the NICU was 43% in 1998, 50% in 1999, 38% in 2000, 42% in 2001, and 17% in 2002. Again, the researchers attributed the decrease after 2001 to a better index of suspicion for the fungal infections.
High incidence and mortality in very-low-birth-weight infants raise the question of prophylactic treatment in this high-risk population, Dr. Deville said.
That automatically raises concerns about resistance. “It's a very valid concern, but prophylaxis will decrease the overall incidence,” he said. “I don't think it outweighs the decision to 'prophylax'—overall you will see less [invasive candidiasis] and prevent mortality.”
“The take-home message is once you have a sick newborn [who appears] to have an infection, consider candida,” Dr. Deville said. The typical patient is a premature infant in the NICU for a month or 2 with multiple bacterial infections, fevers, and lowered blood pressure.
Early empiric therapy might reduce morbidity and mortality in these neonates. Treatment with amphotericin B is an option, but the drug has a lot of side effects, he said. Also, amphotericin B is delivered by a slow infusion that can take up to 4 hours to administer. Azole therapy is quicker but must be given intravenously in this population.
“We're excited about the echinocandins—they are less toxic than other agents,” he said.