The incidence of invasive candidiasis declined substantially in recent years among more than 700,000 infants treated in 322 neonatal intensive care units of a national health care system, according to a report published online January 20 in Pediatrics.
The study sample included such a large proportion of all low-birth-weight (LBW) neonates that "our findings are likely representative of the actual burden of disease in this population," so the results provide "evidence for an overall downward trend of invasive candidiasis in the NICU population across the country," said Dr. Sofia Aliaga of the division of neonatal-perinatal medicine at the University of North Carolina, Chapel Hill, and her associates.
The decline in candidiasis cases was associated with a concomitant rise in the use of antifungal prophylaxis, an increase in empirical antifungal therapy, and a decrease in the use of broad-spectrum antibacterial antibiotics in this patient population. Although a retrospective cohort study such as this cannot determine causality, these changes in clinical practice probably contributed heavily to the decline in invasive neonatal candidiasis, they noted.
To track rates of neonatal candidiasis over time, Dr. Aliaga and her colleagues assessed 709,325 infants treated in NICUs across the country from 1997 through 2010. The researchers identified 2,063 neonates (0.3%) who developed invasive candidiasis.
During the study period, the annual incidence of invasive candidiasis declined from 3.6 to 1.4 cases per 1,000 infants. The greatest decrease occurred in the smallest infants: from 82.7 to 23.8 cases per 1,000 neonates weighing less than 750 g and from 24.2 to 11.6 per 1,000 neonates weighing 750-999 g, the investigators said (Pediatrics 2014;133:236-42).
At the same time, the use of fluconazole antifungal prophylaxis rose from 0.1 to 7.4 per 1,000 infants. The use of empirical antifungal therapy rose from 4.0 to 11.5 per 1,000 infants, and the use of broad-spectrum antibiotics decreased from 275.7 to 48.5 per 1,000 infants.
"Exposure to broad-spectrum antibacterial antibiotics was associated with an increased risk of invasive candidiasis (adjusted odds ratio: 1.88)," the researchers said.
Among the smallest infants, each 10% decrease in the use of broad-spectrum antibacterial antibiotics was associated with a 3%-7% decrease in the incidence of the disease. In addition, the results of a regression analysis "imply that, on average, sites that reduced broad-spectrum antibiotic use the most had the largest decrease in candidiasis," Dr. Aliaga and her associates said.
Other factors also may have contributed to the decline in the disease. For example, several NICU quality-improvement initiatives that were implemented in the past 15 years targeted the management of central catheters and were intended to decrease central line–associated bloodstream infections, so they may have helped reduce invasive candidiasis. Compliance with higher dosing recommendations for fluconazole therapy and the introduction of newer antifungal agents such as echinocandins during the study period also may have contributed.
Other contributing factors may have included greater attention to hand-washing protocols in recent years, decreased exposure to other risk factors such as the use of histamine-2 blocking agents and the use of mechanical ventilation, and changes in feeding practices in the NICU.
Even though this cohort study could not demonstrate the reason for the robust decline in invasive candidiasis among NICU patients, it is unlikely that prospective clinical trials to make that determination will be feasible because the current incidence is so low. "Given a cumulative incidence of 1.4 infections per 1,000 infants, a 250-infant study would require 10 years and 100 NICUs [just] to complete enrollment," Dr. Aliaga and her associates noted.
This study was supported by the National Institutes of Health, the U.S. Department of Health and Human Services, and the American Recovery and Reinvestment Act. Dr. Aliaga reported no potential financial conflicts of interest. Her associates reported industry funding for the development of neonatal and pediatric drugs, as well as ties to Astellas (maker of micafungin), Pfizer (maker of anidulafungin and fluconazole), Merck (maker of caspofungin), and Novartis and Gilead (makers of other antifungal agents used against neonatal candidiasis.