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  • Original Article
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Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis

Abstract

Background:

Extremely low birth weight (ELBW) infants are at increased risk for invasive candidiasis and associated morbidity and mortality. The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians.

Objectives:

To evaluate the effectiveness and safety of fluconazole prophylaxis in ELBW infants.

Study design:

ELBW infants (BW1000 g) born during the pre-prophylaxis era (PPE, January 1998–February 2002) were compared with prophylaxis era (PE, March 2002–September 2005). Infants born during PE received fluconazole prophylaxis for 6 weeks, as long as they had intravenous access. Demographic and clinical data were collected. The two groups were compared for baseline demographics, risk factors for candidiasis, the incidence of invasive candidiasis, liver enzymes, alkaline phosphatase, and bilirubin (total and direct).

Results:

Nine out of 137 infants (6.6%) developed invasive candidiasis during PPE compared to none of 140 (0%) during PE (P=0.006). During PE, 60/140 (42.9%) infants developed conjugated hyperbilirubinemia compared to 12/137 (8.8%) during PPE (P<0.001).

Conclusion:

Although a fluconazole prophylaxis regimen for ELBW infants was effective in preventing invasive candidiasis, an increase in the incidence of conjugated hyperbilirubinemia was observed. Further studies are needed to evaluate the safety of fluconazole prophylaxis in this population.

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References

  1. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA et al. Late-onset sepsis in very low birth weigh neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Part 1): 285–291.

    Article  Google Scholar 

  2. Benjamin DK, Stoll BJ, Fanaroff AA, McDonald SA, Oh W, Higgins RD, et al., on behalf of the NICHD Neonatal Research Network. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18–22 months. Pediatrics 2006; 117 (1): 84–92.

    Article  Google Scholar 

  3. Baley JE . Neonatal candidiasis: the current challenge. Clin Perinatol 1991; 18: 263–280.

    Article  CAS  Google Scholar 

  4. Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz LG . Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med 2001; 345 (23): 1660–1666.

    Article  CAS  Google Scholar 

  5. Bendel CM . Nosocomial neonatal candidiasis. Pediatr Infect Dis J 2005; 24 (9): 831–832.

    Article  Google Scholar 

  6. Feja KN, Wu F, Roberts K, Loughrey M, Nesin M, Larson E et al. Risk factors for candidemia in critically ill infants: a matched case–control study. J Pediatr 2005; 147: 156–161.

    Article  Google Scholar 

  7. Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Grossman LB . Twice weekly fluconazole prophylaxis for prevention of invasive candida infection in high-risk infants of &lt;1000 g birth weight. J Pediatr 2005; 147: 172–179.

    Article  CAS  Google Scholar 

  8. Kicklighter SD, Springer SC, Cox T, Husley TC, Turner RB . Fluconazole for prophylaxis against canidal rectal colonization in the very low birth weight infant. Pediatrics 2001; 107: 293–298.

    Article  CAS  Google Scholar 

  9. McGuire W, Clerihew L, Austin N . Prophylactic intravenous antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev 2004; (1): CD003850.

  10. Manzoni P, Arisio R, Mostert M, Leonessa M, Farina D, Latino MA et al. Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study. Pediatrics 2006; 117: e22–e32.

    Article  Google Scholar 

  11. Healy CM, Baker CJ, Zaccaria E, Campbell JR . Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit. J Pediatr 2005; 147: 166–171.

    Article  CAS  Google Scholar 

  12. Bertini G, Perugi S, Dani C, Filippi L, Prates S, Rubatelli F . Fluconazole prophylaxis prevents invasive fungal infection in high-risk, very low birth weight infants. J Pediatr 2005; 147: 162–165.

    Article  CAS  Google Scholar 

  13. Uko S, Soghier LM, Vega M, Marsh J, Reinersman GT, Herring L et al. Targeted short-term fluconazole prophylaxis among low birth weight and extremely low birth weight infants. Pediatrics 2006; 117 (4): 1243–1252.

    Article  Google Scholar 

  14. McKiernan PJ . Neonatal cholestasis. Semin Neonatol 2002; 7: 153–165.

    Article  CAS  Google Scholar 

  15. Fanaroff AA . Fluconazole for the prevention of fungal infections: get ready, get set, caution. Pediatrics 2006; 117: 214–215.

    Article  Google Scholar 

  16. Long SS, Stevenson DK . Reducing candida infections during neonatal intensive care: management choices, infection control and fluconazole prophylaxis. J Pediatr 2005; 147: 135–141.

    Article  Google Scholar 

  17. Saiman L, Ludington E, Pfaller M, Rangel-Frausto S, Wiblin RT, Dawson J et al. Risk factors for candidemia in neonatal intensive care unit patients. The National Epidemiology of Mycosis Survey Study Group. Pediatr Infect Dis J 2000; 19: 319–324.

    Article  CAS  Google Scholar 

  18. Karlowicz MG, Rowen JL, Barnes-Eley ML, Burke BL, Laeson ML, Bendel CM et al. The role of birth weight and gestational age in distinguishing extremely low birth weight infants at high risk of developing candidemia from infants at low risk: a multicenter study. Pediatr Res 2002; 51: 301A.

    Google Scholar 

  19. Chapman RL, Faix RG . Persistently positive cultures and outcome in invasive neonatal candidiasis. Pediatr Infect Dis J 2000; 19 (9): 822–827.

    Article  CAS  Google Scholar 

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Correspondence to Z H Aghai.

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Aghai, Z., Mudduluru, M., Nakhla, T. et al. Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis. J Perinatol 26, 550–555 (2006). https://doi.org/10.1038/sj.jp.7211570

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  • DOI: https://doi.org/10.1038/sj.jp.7211570

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