Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

Abstract

Objective: Previous reports suggest a benefit of fluconazole prophylaxis in extremely low birth weight (ELBW) infants <1000 g. Our aim was to evaluate if limiting fluconazole prophylaxis to targeted highest risk infants effectively prevents invasive fungal infections, has no undesired side effects and limits unnecessary drug exposure.Study Design: This nonrandomized retrospective pre-post intervention study compared two groups of infants: (1) Infants <26 weeks gestation and/or <750 g birth weight, requiring central vascular access and admitted to the Monroe Carell Jr Children's Hospital at Vanderbilt neonatal intensive care unit (NICU) prior to 5 days of age, who received fluconazole prophylaxis and (2) a matched control group from the year prior to prophylaxis. This target population was selected for fluconazole prophylaxis based on prior infection control data from our institution and a number needed to treat of <15 to prevent one episode of fungemia. Following implementation and integration through the institution's computerized physician order entry (CPOE) system, provider adherence to the protocol was assessed during the prophylaxis period.Result: A total of 86 patients were included in the study, 44 in the no-prophylaxis group and 42 in the prophylaxis group. In the targeted prophylaxis group, no invasive fungal infections were observed as compared to nine infants with invasive infections in the no-prophylaxis group (P ¼ 0.004). No significant adverse effects were recorded. Targeting the highest risk infants reduced the number of infants <1000 g requiring prophylaxis from 80 to 42 (48% reduction) with no preventable infection missed. Provider compliance was 91% following implementation of this protocol through the CPOE system using a standardized order set. Conclusion:Targeting the highest risk infants for fluconazole prophylaxis through CPOE can effectively prevent invasive fungal infections and limit drug exposure with no unwanted side effects.

Prevention of invasiveCandidainfections in preterm infants: the time is now

“…In infants weighing under 1000 g with ICI, mortality rates range from 23 to 66% of the control patients in prophylaxis studies [5][6][7][8][9][10][11][12][13][14][15]. There is a marked difference in mortality between infants weighing under 1000 g and larger infants with ICI.…”

“…Weitkamp et al recently reported the importance of examining ICI incidence in each NICU, as many flaws exist when solely relying on the literature for incidence rates [15]. The NICU reported that their rate of Candida BSI was 6.8%, while the rate of all ICIs was 10% for infants weighing under 1000 g.…”

Impact of ‘targeted’ fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?

“…Rates of invasive candidiasis in two randomized controlled trials and one targeted retrospective study ranged from 13.2 to 20%. 6,13,15 A much lower incidence of 7% Candida bloodstream infections is reported among the NICHD Neonatal Research Network centers for PT infants with birth weights <1000 g. 1 According to the National Mycoses Study Group, 3.1% of VLBW (<1500 g) infants develop Candida bloodstream infections, whereas a 1% rate were reported in the UK prospective surveillance study. 21,22 Whether our results can be extrapolated to other centers with low rates remains to be determined.…”

“…The OR for invasive fungal infection was similar to 4-to 6-week fluconazole courses, with a lower number of doses (median 6) per infant; 51% of all VLBW infants received prophylaxis. Weitkamp et al 15 used a targeted approach of FP to 42 PT infants (<750 g birth weight or <26 weeks gestational age with a central line access) for 6 weeks, and again demonstrated a reduction in invasive fungal infections, compared with historic controls. In our center, the mean birth weight and gestational age of infants with invasive candidiasis in the control period was 786 g and 26 weeks, respectively.…”

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

“…To date there have been five randomized controlled trials (RCTs) [52,[65][66][67][68], eight retrospective reviews [19,20,[73][74][75][76][77][78], and a Cochrane review [79] examining fluconazole prophylaxis in neonates.…”