March 21, 2008

Common anti-fungal drug aids ‘preemies’

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Hendrik Weitkamp, M.D., examines patient Demariyona Shields in the NICU. (photo by Dana Johnson)

Common anti-fungal drug aids ‘preemies’

A new protocol to protect the tiniest premature infants from the threat of fungal infection is saving lives and has nearly eradicated the infection from the neonatal intensive care unit.

Hendrik Weitkamp, M.D., assistant professor of Neonatology at the Monroe Carell Jr. Children's Hospital at Vanderbilt, said an effort to improve quality assurance led the NICU to begin using a common antifungal medication in what some might view as a risky population — extremely low-birthweight babies.

“When these tiny babies get a fungal infection, they can be very sick,” Weitkamp said. “They have many of the same systemic symptoms of sepsis, like serious changes in blood pressure and organ failure. Usually when a baby looks septic we initially think about a bacterial infection, but 12 percent of invasive infections in NICUs are from a fungal organism, the most common of which is Candida albicans.”

After reviewing infection data, the decision was made to begin a protocol of giving the highest-risk babies — defined as those weighing less than 750 grams at birth and/or fewer than 26 weeks gestation — a preventive dose of fluconazole twice a week for six weeks while they have invasive tubes that make them high risk for blood infection.

Some hospitals already use preventive fluconazole, but they included all premature infants weighing less than 1,500 grams at birth, twice the weight limit set by Vanderbilt's NICU.

Vanderbilt began the protocol in 2005. To prove that giving fluconazole as a preventive was of clear benefit to such tiny babies, Weitkamp teamed with Amy Potts, Pharm.D., from the Children's Hospital Pharmacy, and Asli Ozdas, Ph.D., from the Department of Biomedical Informatics, on a retrospective study comparing the first 42 babies to receive the new prevention with 44 babies of the same description from the previous year.

The results were recently published in the online Journal of Perinatology.

“We had no cases of invasive fungal infection for the 40 babies who got prophylactic fluconazole, but the comparison group the year before had nine infants who developed invasive Candida albicans infection,” Weitkamp said.

Potential side effects of the drug include occasional mild kidney, blood or liver malfunctions.

“We felt the results were a strong reason to continue to use the drug as a preventive in a targeted, highest-risk population,” Weitkamp said. “Since we started the protocol, we almost completely eradicated Candida infections from our nursery. Our infection rates are now less than half of what other large academic children's hospitals in the country report."

But there are lingering concerns of development of drug resistance.

Weitkamp said the question is just as important in the treatment of fungal infections, so prophylaxis is being carefully monitored for any signs that it encourages more difficult strains of Candida to flourish, or that Candida albicans might become resistant to fluconazole itself.