Fluconazole Prophylaxis against Fungal Colonization and Infection in Preterm Infants

Kaufman, David; Boyle, Robert; Hazen, Kevin C.; Patrie, James T.; Robinson, Morton J.; Donowitz, Leigh G.

doi:10.1056/nejmoa010494

Cited by 477 publications

(403 citation statements)

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“…7,[9][10][11][12]14,15,18 In solid organ and bone marrow transplant patients, antifungal prophylaxis with fluconazole has been successfully used for years to prevent colonization and infection due to Candida species and markedly reduced the need for empiric amphotericin B therapy. 19,20 However, because of the lack of larger multicenter randomized trials and data on long-term Fluconazole prophylaxis for highest risk infants J-H Weitkamp et al neurodevelopmental outcomes as well as concerns about unwanted side effects and development of Candida resistance, fluconazole prophylaxis in high-risk infants remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…7,9,10 In our protocol, patients with a birth weight between 750 and 1000 g were not included unless they were less than 26.0 weeks gestational age. Using the same prophylaxis protocol entry criteria for infants between 750 and 1000 g birth weight, 47 additional infants would have been targeted for fluconazole prophylaxis between 1 November 2005 and 31 October 2006.…”

Section: Limiting Drug Exposure By Targeting Highest Risk Infantsmentioning

confidence: 99%

“…[2][3][4] Early colonization of the skin and mucous membranes with Candida species can progress to candidemia in up to 60% of ELBW infants. [5][6][7] In addition to mortality, neonatal candidemia has been associated with increased NICU lengths of stay and hospital costs. 8 Kaufman et al 7 published the only prospective, randomized, double-blind clinical trial to date that demonstrates effectiveness and safety of fluconazole administration in preventing fungal colonization and invasive fungal infection in ELBW infants during the first 6 weeks of life.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7] In addition to mortality, neonatal candidemia has been associated with increased NICU lengths of stay and hospital costs. 8 Kaufman et al 7 published the only prospective, randomized, double-blind clinical trial to date that demonstrates effectiveness and safety of fluconazole administration in preventing fungal colonization and invasive fungal infection in ELBW infants during the first 6 weeks of life. Later, the same group suggested a twice weekly dosing protocol with similar efficacy but decreased cost and less drug exposure.…”

Section: Introductionmentioning

confidence: 99%

“…Previous reports suggest a benefit of fluconazole prophylaxis in ELBW infants <1000 g at high risk of fungal infections. 7 But instead of adopting a fluconazole prophylaxis protocol used by others, 9 we followed the recommendation by McGuire et al 17 to select a target population that would benefit most from fluconazole prophylaxis. For infants <26 weeks gestational age and/or <750 g birth weight, we calculated a number needed to treat of 12 to prevent one episode of fungemia and 26 to prevent one death from fungemia.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Limiting Drug Exposure By Targeting Highest Risk Infantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2008

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Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

Benjamin

Hudak

Duara

et al. 2014

JAMA

110

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IMPORTANCE Invasive candidiasis in premature infants causes mortality and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole is unknown. OBJECTIVE To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes—defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18–22-months corrected age. RESULTS Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%–22%) vs 21% in the placebo group (95% CI, 15%–28%; odds ratio 0.73 [95% CI 0.43–1.23]; P=.24; treatment difference −5% [95% CI, −13%–3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%–6%] vs the placebo group (9% [95% CI, 5%–14%]; P=.02; treatment difference −6% [95% CI, −11%–−1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole 31% [95% CI, 21–41%] vs placebo, 27% [95% CI, 18–37%]; P=.60; treatment difference 4% [95% CI, −10–17%]). CONCLUSIONS AND RELEVANCE Among infants with a birth weight of less 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely-low-birth-weight infants. TRIAL REGISTRATION ClinicalTrials.gov number NCT00734539

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Prophylactic oral antifungal agents to prevent systemic candida infection in preterm infants

Austin

Darlow²

2003

Cochrane Database of Systematic Reviews

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Fluconazole Prophylaxis against Fungal Colonization and Infection in Preterm Infants

Abstract: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.

Cited by 477 publications

References 37 publications

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

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

Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

Prophylactic oral antifungal agents to prevent systemic candida infection in preterm infants

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