Home⇛The PCMC Journal⇛vol. 10 no. 1 (2011)

A Randomized Controlled Trial on the Prophylactic Use of Fluconazole in the Prevention of Invasive Fungal Disease Among Very Low Birthweight Newborns Admitted at PCMC

Jeorge S Ducha | Emilio A. Hernandez

Discipline: medicine by specialism

 

Abstract:

Background: Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing invasive fungal infection in very low birth weight and extremely low birth weight infants. preterm infants with birth weight less than 1500 grams in a tertiary referral hospital. The infants were assigned during the first two weeks of life to receive intravenous or oral fluconazole or placebo. We obtained weekly surveillance cultures and liver enzyme tests. Results: There were no significant differences between the control and fluconazole groups in baseline demographic characteristics or risk factors for fungal infection. Fungal infection developed in 24 (16 blood, 7 urine and 1 in CSF) among the control group and two (blood) in the treatment group. There were 12 mortalities which can be related to fungal infection in the control group; the two mortalities in the treatment group were caused by conditions not related to fungemia. The only adverse reaction was mild elevation of liver enzymes which reverts to normal after discontinuation of the drug. This is more prominent in extremely low birth weight neonates.



References:

  1. Fanaroff AA, et al. Incidence, presenting features, risk factors and significance of late-onset septicemia in very low birth weight infants. Pediatr Infect Dis J. 1998;17:593-598.
  2. Ronnestad A, et al. Blood culture isolates during 6 years in a tertiary neonatal intensive care unit. Scand J Infect Dis. 1998;30:245-251.
  3. Stoll BJ, et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr. 1996;129:63-71.
  4. Faix RG. Mucocutaneous and invasive candidiasis among very low birth weight (<1500 grams) infants in intensive care nurseries: a prospective study. Pediatrics. 1989;83:101-107.
  5. Lee BE, et al. Comparative study of mortality and morbidity in premature infants (birth weight <1,250 g) with candidemia or candidal meningitis. Clin Infect Dis. 1998;27:559-565.
  6. Weese-Mayer DE, et al. Risk factors associated with candidemia in the neonatal intensive care unit: a case-control study. Pediatr Infect Dis J. 1987;6:190-196.
  7. Baley JE, et al. Fungal colonization in very low birth weight infants. Pediatrics. 1986;75:225-232.
  8. El-Mohandes, et al. Incidence of Candida parapsilosis colonization in an intensive care nursery population and its association with invasive fungal disease. Pediatr Infect Dis J. 1994;13:520-524.
  9. Hageman JR, et al. Candidal colonization and infection in very low birth weight infants. J Perinatol. 1994;14:251-254.
  10. Huang Y, et al. Association of fungal colonization and invasive disease in very low birth weight infants. Pediatr Infect Dis J. 1998;17:819-822.
  11. Rowen JL, et al. Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates. J Pediatr. 1994;124:789-794.
  12. Sims ME, et al. Prophylactic oral nystatin and fungal infections in very low birth weight infants. Am J Perinatol. 1988;5:33-36.
  13. Wainer S, et al. Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection. Pediatr Infect Dis J. 1992;11:713-716.
  14. Driessen M, et al. Fluconazole vs amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Pediatr Infect Dis J. 1996;15:1107-1112.
  15. Wainer S, et al. Prospective study of fluconazole therapy in systemic neonatal fungal infection. Pediatr Infect Dis. 1997;16:763-767.
  16. Huttova M, et al. Candida fungemia in neonates treated with fluconazole: report of forty cases, including eight with meningitis. Pediatr Infect Dis J. 1998;17:1012-1015.
  17. Saxen H, et al. Pharmacokinetics of fluconazole in very low birth weight infants during the first two weeks of life. Clin Pharmacol Ther. 1993;53:259-276.
  18. Kaufman D, et al. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. N Engl J Med. 2001;345:1160-1166.
  19. Brammer KW, et al. Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis. 1994;13:325-329.
  20. Healy CM, et al. Impact of fluconazole prophylaxis on incidence and outcome of invasive candidiasis in a neonatal intensive care unit. J Pediatr. 2005;146:166-171.
  21. Kicklighter S, et al. Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant. Pediatrics. 2001;107:293-298.
  22. Manzoni P, et al. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med. 2007;356:2483-2495.
  23. Berger RL, Boos DD. P values maximized over a confidence set for the nuisance parameter. J Am Stat Assoc. 1994;89:1012-1016.
  24. Santner TJ, Snell MK. Small-sample confidence intervals for p1-p2 and p1/p2 in 2×2 contingency tables. J Am Stat Assoc. 1980;75:386-394.
  25. Pfizer Philippines. Fluconazole (Diflucan) Pharmacokinetics.
  26. Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326:845-851.
  27. Kern W, Behre G, Rudolf T, et al. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia: results of a prospective randomized phase III study. Cancer. 1998;83:291-301.
  28. Kanda Y, Yamamoto R, Chizuka A, et al. Prophylactic action of oral fluconazole against fungal infection in neutropenic patients: a meta-analysis of 16 randomized controlled trials. Cancer. 2000;89:1611-1625.
  29. Castagnola E, Machetti M, Bucci B, Viscoli C. Antifungal prophylaxis with azole derivatives. Clin Microbiol Infect. 2004;10(Suppl 1):86-95.
  30. Fanaroff AA. Fluconazole for the prevention of fungal infections: get ready, get set, caution. Pediatrics. 2006;117:214-215.
  31. Long SS, Stevenson DK. Reducing Candida infections during neonatal intensive care: management choices, infection control and fluconazole prophylaxis. J Pediatr. 2005;147:135-141.
  32. 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 <1000 grams birth weight. J Pediatr. 2005;147:172-179.
  33. 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.
  34. 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.
  35. 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.
  36. Cotton CM, McDonald S, Stoll B, Goldberg RN, Poole K, Benjamin DK Jr, et al. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth weight infants. Pediatrics. 2006;118:717-722.
  37. Feja KN, Wu F, Roberts K, et al. Risk factors for candidemia in critically ill infants: a matched case-control study. J Pediatr. 2005;147:156-161.
  38. Fridkin SK, Kaufman D, Edwards JR, Shetty S, Horan T. Changing incidence of Candida bloodstream infections among NICU patients in the United States: 1995-2004. Pediatrics. 2006;117:1680-1687.
  39. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161-189.

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