Consider Narrow Fluconazole Strategy if Candida Incidence Is Low

BOSTON – A narrow, targeted approach to fluconazole prophylaxis prevents most cases of neonatal candidiasis among extremely low-birth-weight infants in centers with a low incidence of the fungal infection, a study has shown.

Because of the high rates of mortality and neurodevelopmental impairment associated with candidiasis infection in at-risk infants, the Infectious Diseases Society of America recommends that centers with a high incidence of the infection consider routine fluconazole prophylaxis for extremely low-birth-weight neonates (less than 1,000 g at birth). The recommendation does not extend to low-incidence centers, however, because of the unknown risks for neurologic and cognitive disorders after fluconazole exposure in premature infants, said Dr. Karen M. Puopolo, a neonatologist at Brigham and Women’s Hospital in Boston.

To assess the theoretical efficacy of fluconazole prophylaxis in extremely low-birth-weight (ELBW) infants in a low-incidence center, Dr. Puopolo and her colleagues reviewed the clinical details of blood culture–proven neonatal Candida infections that occurred in a single tertiary care neonatal intensive care unit (NICU) from January 2003 to October 2010.

Using demographic data and antibiotic exposure information gleaned from medical and administrative records of nearly 1,400 ELBW infants, "we developed four different possible criteria for fluconazole prophylaxis, including fluconazole prophylaxis for all babies born with a birth weight less than 1,000 g, all babies born with a birth weight less than 1,000 g who also received 7 or more days of antibiotics, all babies born with a birth weight less than 750 g, and all babies born with a birth weight less than 750 g who also received 7 or more days of antibiotics," she explained at the annual meeting of the Pediatric Academic Societies.

For the number needed to treat (NNT) calculations, the investigators assumed that fluconazole prophylaxis would be 100% effective, and for the antibiotic exposure calculation, which was based on a review of antibiotic use in the NICU, they assumed that 50% of the infants with a birth weight less than 1,000 g and 80% with a birth weight less than 750 g would be treated with antibiotics for 7 or more days, Dr. Puopolo said.

During the period of study, 1,381 ELBW infants were exposed to fluconazole prophylaxis, including 878 weighing less than 1,000 g at birth, of which 293 had a minimum of 7 days of antibiotic therapy, and 393 weighing less than 750 g at birth, of which 179 had a minimum of 7 days of antibiotic therapy, Dr. Puopolo said. "Twenty cases of neonatal candidiasis were identified, with 18 [3%] occurring in ELBW infants surviving beyond 72 hours of life," she said. The mean birth weight of the infected infants was 702 g, and the mean gestational age and age at infection were 24.5 weeks and 21.4 weeks.

With respect to the number needed to treat analysis, the narrowest targeted approach – routine fluconazole prophylaxis in neonates weighing less than 750 g who had been exposed to a minimum of 7 days of antibiotic therapy – was the most efficient. In this subgroup, according to Dr. Puopolo, "we would need to treat 13 infants to prevent one fungal infection." The NNT in the 750-g, 1000-g with 7 or more days of antibiotic exposure, and 1,000-g groups were 15, 19, and 33, respectively.

If this approach were applied to the number of babies in each of the four prophylaxis categories, all 18 infections would have been targeted in the most liberal exposure group, while 567 of the babies would have been unnecessarily exposed to the antifungal drug. In the increasingly narrower exposure groups, 16, 15, and 14 of the infections would have been targeted. Although 2, 3, and 4 of the infections, respectively, would have been missed in these groups, far fewer babies would have been unnecessarily exposed to fluconazole, said Dr. Puopolo.

National guidelines do not recommend fluconazole prophylaxis in centers with a lower-than-average incidence of neonatal invasive Candida infections in the NICU, but "our findings suggest that individual NICUs should consider different approaches to fluconazole prophylaxis based on their incidence of candidiasis," Dr. Puopolo said. "A narrow targeted approach can prevent most cases of neonatal candidiasis with the lowest number needed to treat."

Dr. Puopolo said she had no relevant financial disclosures.

BOSTON – A narrow, targeted approach to fluconazole prophylaxis prevents most cases of neonatal candidiasis among extremely low-birth-weight infants in centers with a low incidence of the fungal infection, a study has shown.

Because of the high rates of mortality and neurodevelopmental impairment associated with candidiasis infection in at-risk infants, the Infectious Diseases Society of America recommends that centers with a high incidence of the infection consider routine fluconazole prophylaxis for extremely low-birth-weight neonates (less than 1,000 g at birth). The recommendation does not extend to low-incidence centers, however, because of the unknown risks for neurologic and cognitive disorders after fluconazole exposure in premature infants, said Dr. Karen M. Puopolo, a neonatologist at Brigham and Women’s Hospital in Boston.

To assess the theoretical efficacy of fluconazole prophylaxis in extremely low-birth-weight (ELBW) infants in a low-incidence center, Dr. Puopolo and her colleagues reviewed the clinical details of blood culture–proven neonatal Candida infections that occurred in a single tertiary care neonatal intensive care unit (NICU) from January 2003 to October 2010.

Using demographic data and antibiotic exposure information gleaned from medical and administrative records of nearly 1,400 ELBW infants, "we developed four different possible criteria for fluconazole prophylaxis, including fluconazole prophylaxis for all babies born with a birth weight less than 1,000 g, all babies born with a birth weight less than 1,000 g who also received 7 or more days of antibiotics, all babies born with a birth weight less than 750 g, and all babies born with a birth weight less than 750 g who also received 7 or more days of antibiotics," she explained at the annual meeting of the Pediatric Academic Societies.

For the number needed to treat (NNT) calculations, the investigators assumed that fluconazole prophylaxis would be 100% effective, and for the antibiotic exposure calculation, which was based on a review of antibiotic use in the NICU, they assumed that 50% of the infants with a birth weight less than 1,000 g and 80% with a birth weight less than 750 g would be treated with antibiotics for 7 or more days, Dr. Puopolo said.

During the period of study, 1,381 ELBW infants were exposed to fluconazole prophylaxis, including 878 weighing less than 1,000 g at birth, of which 293 had a minimum of 7 days of antibiotic therapy, and 393 weighing less than 750 g at birth, of which 179 had a minimum of 7 days of antibiotic therapy, Dr. Puopolo said. "Twenty cases of neonatal candidiasis were identified, with 18 [3%] occurring in ELBW infants surviving beyond 72 hours of life," she said. The mean birth weight of the infected infants was 702 g, and the mean gestational age and age at infection were 24.5 weeks and 21.4 weeks.

With respect to the number needed to treat analysis, the narrowest targeted approach – routine fluconazole prophylaxis in neonates weighing less than 750 g who had been exposed to a minimum of 7 days of antibiotic therapy – was the most efficient. In this subgroup, according to Dr. Puopolo, "we would need to treat 13 infants to prevent one fungal infection." The NNT in the 750-g, 1000-g with 7 or more days of antibiotic exposure, and 1,000-g groups were 15, 19, and 33, respectively.

If this approach were applied to the number of babies in each of the four prophylaxis categories, all 18 infections would have been targeted in the most liberal exposure group, while 567 of the babies would have been unnecessarily exposed to the antifungal drug. In the increasingly narrower exposure groups, 16, 15, and 14 of the infections would have been targeted. Although 2, 3, and 4 of the infections, respectively, would have been missed in these groups, far fewer babies would have been unnecessarily exposed to fluconazole, said Dr. Puopolo.

National guidelines do not recommend fluconazole prophylaxis in centers with a lower-than-average incidence of neonatal invasive Candida infections in the NICU, but "our findings suggest that individual NICUs should consider different approaches to fluconazole prophylaxis based on their incidence of candidiasis," Dr. Puopolo said. "A narrow targeted approach can prevent most cases of neonatal candidiasis with the lowest number needed to treat."

Dr. Puopolo said she had no relevant financial disclosures.

BOSTON – A narrow, targeted approach to fluconazole prophylaxis prevents most cases of neonatal candidiasis among extremely low-birth-weight infants in centers with a low incidence of the fungal infection, a study has shown.

Because of the high rates of mortality and neurodevelopmental impairment associated with candidiasis infection in at-risk infants, the Infectious Diseases Society of America recommends that centers with a high incidence of the infection consider routine fluconazole prophylaxis for extremely low-birth-weight neonates (less than 1,000 g at birth). The recommendation does not extend to low-incidence centers, however, because of the unknown risks for neurologic and cognitive disorders after fluconazole exposure in premature infants, said Dr. Karen M. Puopolo, a neonatologist at Brigham and Women’s Hospital in Boston.

To assess the theoretical efficacy of fluconazole prophylaxis in extremely low-birth-weight (ELBW) infants in a low-incidence center, Dr. Puopolo and her colleagues reviewed the clinical details of blood culture–proven neonatal Candida infections that occurred in a single tertiary care neonatal intensive care unit (NICU) from January 2003 to October 2010.

Using demographic data and antibiotic exposure information gleaned from medical and administrative records of nearly 1,400 ELBW infants, "we developed four different possible criteria for fluconazole prophylaxis, including fluconazole prophylaxis for all babies born with a birth weight less than 1,000 g, all babies born with a birth weight less than 1,000 g who also received 7 or more days of antibiotics, all babies born with a birth weight less than 750 g, and all babies born with a birth weight less than 750 g who also received 7 or more days of antibiotics," she explained at the annual meeting of the Pediatric Academic Societies.

For the number needed to treat (NNT) calculations, the investigators assumed that fluconazole prophylaxis would be 100% effective, and for the antibiotic exposure calculation, which was based on a review of antibiotic use in the NICU, they assumed that 50% of the infants with a birth weight less than 1,000 g and 80% with a birth weight less than 750 g would be treated with antibiotics for 7 or more days, Dr. Puopolo said.

During the period of study, 1,381 ELBW infants were exposed to fluconazole prophylaxis, including 878 weighing less than 1,000 g at birth, of which 293 had a minimum of 7 days of antibiotic therapy, and 393 weighing less than 750 g at birth, of which 179 had a minimum of 7 days of antibiotic therapy, Dr. Puopolo said. "Twenty cases of neonatal candidiasis were identified, with 18 [3%] occurring in ELBW infants surviving beyond 72 hours of life," she said. The mean birth weight of the infected infants was 702 g, and the mean gestational age and age at infection were 24.5 weeks and 21.4 weeks.

With respect to the number needed to treat analysis, the narrowest targeted approach – routine fluconazole prophylaxis in neonates weighing less than 750 g who had been exposed to a minimum of 7 days of antibiotic therapy – was the most efficient. In this subgroup, according to Dr. Puopolo, "we would need to treat 13 infants to prevent one fungal infection." The NNT in the 750-g, 1000-g with 7 or more days of antibiotic exposure, and 1,000-g groups were 15, 19, and 33, respectively.

If this approach were applied to the number of babies in each of the four prophylaxis categories, all 18 infections would have been targeted in the most liberal exposure group, while 567 of the babies would have been unnecessarily exposed to the antifungal drug. In the increasingly narrower exposure groups, 16, 15, and 14 of the infections would have been targeted. Although 2, 3, and 4 of the infections, respectively, would have been missed in these groups, far fewer babies would have been unnecessarily exposed to fluconazole, said Dr. Puopolo.

National guidelines do not recommend fluconazole prophylaxis in centers with a lower-than-average incidence of neonatal invasive Candida infections in the NICU, but "our findings suggest that individual NICUs should consider different approaches to fluconazole prophylaxis based on their incidence of candidiasis," Dr. Puopolo said. "A narrow targeted approach can prevent most cases of neonatal candidiasis with the lowest number needed to treat."

Dr. Puopolo said she had no relevant financial disclosures.