Prophylaxis, other measures help decrease Candida rate in NICUs

David A. Kaufman, MD

This CDC study lead by Chitnis and colleagues demonstrates the fruits of the NHSN’s (National Healthcare Safety Network’s) work and infection database. This study demonstrated the decrease in rates of Candida CLABSIs over the 10-year time period between 1999 and 2009. The reduction was most significant for those infants weighing less than 1,000 g, but was lower for most of the other birth weight groups as well. The paper discussed that the decrease is most likely due to antifungal prophylaxis, central line bundles and/or infection control measures (eg, reduction in the use of gastric acid inhibitors, postnatal steroids, third-generation and higher cephalosporins and carbapenems). The data from the NHSN currently does not have these practices linked to infection rates, though hopefully in the future these could be linked and examined. These findings support that all three of these practices should be part of every NICU’s guidelines for infection prevention.

It is important to note that while the definition for Candida CLABSI is the best we have currently, Candida species commonly disseminate after colonization of the skin, respiratory and gastrointestinal tracts (without overt cellulitis, pneumonia or NEC) and less often from central venous catheters (even if in place at the time of infection). Due to this, at times it is difficult to assign the central line as the cause when infections arise from those sites. Additionally, antifungal prophylaxis is part of CLABSI bundles in our institution and in some publications (Aly H. Pediatrics. 2005;115(6):1513-8).

In discussing which interventions could contribute to reducing Candida CLABSIs, antifungal prophylaxis is the only one that has been subjected to randomized controlled trials. Examining the trends of the decrease over the 10-year period, one initially sees a small impact possibly related to infection control practices from 1999 to 2000 and then large sharp decreases after 2001 and 2005 most likely related to antifungal prophylaxis in infants weighing less than 1,000 g.

The first study of fluconazole prophylaxis was published in 2001 and then a group of studies in 2005 followed by 2 to 3 per year since that time — (now totaling more than 20 studies in more than 5,000 infants (Kaufman DA. Neoreviews. 2011;12(7):e381-e392). NICU CLABSI interventions and publications started around 2005 to 2009 and may have contributed to the later fall in infections. The paper does point out that while there are a greater number of NICUs reporting infection data to the NHSN and likely instituting CLABSI bundles, not all CLABSI infections have been reduced — MRSA rates have increased and MSSA remained unchanged. This raises the question of the efficacy of the CLABSI bundles alone reducing these Candida infections. 

Another question is: Can antifungal prophylaxis targeted to less than 1,000 g effect infections in infants greater than 1,000 g? Fluconazole prophylaxis leads to reduced colonization, which in turn can reduce horizontal transmission leading to infection to other infants in the NICU, eg, of similar and/or greater birth weights. In our NICU (since 2005), we have also expanded prophylaxis to those infants greater than 1,000 g who have NEC or gastroschisis. With this approach we have observed no Candida infections in infants greater than 1,000 g. The decrease in larger infants could also be due to some NICUs using targeted prophylaxis in infants less than 1,500 g.

The AAP Red Book 2012 released on June 15, 2012, guidelines that included updated information regarding antifungal prophylaxis for preterm infants less than 1,000 g (AAP. Red Book: 2012). This report states that, “On the basis of current data, fluconazole is the preferred agent for prophylaxis, because it has been shown to be effective and safe. Fluconazole prophylaxis is recommended for ELBW infants cared for in NICUs with moderate (5% to10%) or high (10% or greater) rates of invasive candidiasis. The recommended regimen for ELBW neonates is fluconazole administered intravenously during the first 48 to 72 hours after birth at a dose of 3 mg/kg, twice weekly, for 4 to 6 weeks, or until IV access no longer is required for care. This dosage and duration of chemoprophylaxis has not been associated with emergence of fluconazole-resistant Candida species.”

In conclusion, to best eliminate or achieve the lowest rates of Candida CLABSIs, antifungal prophylaxis, CLABSI bundles and infection control practices should be part of every NICU’s guidelines for infection prevention.