Download PDF
Am J Perinatol 2014; 31(12): 1043-1048
DOI: 10.1055/s-0034-1371358
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Efficacy of Prophylactic Fluconazole Therapy in Decreasing the Incidence of Candida Infections in Extremely Low Birth Weight Preterm Infants

Merih Cetinkaya
1   Division of Neonatology, Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
,
Tugba Erener Ercan
1   Division of Neonatology, Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
,
Ozge Kurum Saglam
2   Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
,
Gokhan Buyukkale
1   Division of Neonatology, Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
,
Sultan Kavuncuoglu
2   Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
,
Fatih Mete
2   Department of Pediatrics, Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey
› Author Affiliations
Further Information

Publication History

26 August 2013

06 January 2014

Publication Date:
28 February 2014 (online)

Also available at
    Permissions and Reprints

Abstract

Objective Systemic fungal infections are major causes of morbidity and mortality, and are associated with significant neurodevelopmental impairment in premature infants. Our objective was to evaluate the efficacy of fluconazole prophylaxis in prevention of systemic fungal infections among preterm infants.

Study Design This observational pre-post cohort study was performed in preterm infants with a birth weight of < 1,000 g who were given prophylactic fluconazole starting on the first postnatal day at a dose of 3 mg/kg twice a week. These infants were compared with preterm infants who were not given prophylaxis.

Results Prophylaxis group consisted of 90 infants and control group consisted of 107 infants. Systemic fungal infection was observed in five patients (4.7%) in the control group while no fungal infection was detected in the prophylaxis group (p = 0.03). There were no significant differences between two groups in terms of demographic features, maternal and neonatal risk factors, and all-cause mortality rates. No adverse reactions were seen during the prophylaxis period.

Conclusions We suggest that intravenous fluconazole prophylaxis at a dose of 3 mg/kg twice a week is a safe and effective strategy for decreasing systemic fungal infections even in neonatal intensive care units with low rates of invasive Candida infection.

Keywords

Candida - fluconazole - infection - preterm - prophylaxis
 

  • References

  • 1 Shetty SS, Harrison LH, Hajjeh RA , et al. Determining risk factors for candidemia among newborn infants from population-based surveillance: Baltimore, Maryland, 1998-2000. Pediatr Infect Dis J 2005; 24 (7) 601-604
    CrossrefPubMedSearch in Google Scholar
  • 2 Manzoni P, Jacqz-Aigrain E, Rizzollo S , et al. Antifungal prophylaxis in neonates. Early Hum Dev 2011; 87 (Suppl. 01) S59-S60
    CrossrefPubMedSearch in Google Scholar
  • 3 Stoll BJ, Hansen N, Fanaroff AA , et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110 (2 Pt 1) 285-291
    CrossrefPubMedSearch in Google Scholar
  • 4 Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin Microbiol Rev 2004; 17 (3) 638-680
    CrossrefPubMedSearch in Google Scholar
  • 5 Benjamin Jr DK, Stoll BJ, Fanaroff AA , et al; National Institute of Child Health and Human Development Neonatal Research Network. Neonatal candidiasis among extremely low birth weight infants: risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months. Pediatrics 2006; 117 (1) 84-92
    CrossrefPubMedSearch in Google Scholar
  • 6 Stoll BJ, Hansen NI, Adams-Chapman I , et al; National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292 (19) 2357-2365
    CrossrefPubMedSearch in Google Scholar
  • 7 Castagnola E, Jacqz-Aigrain E, Kaguelidou F , et al. Fluconazole use and safety in the nursery. Early Hum Dev 2012; 88 (Suppl. 02) S11-S15
    CrossrefPubMedSearch in Google Scholar
  • 8 Kaufman DA. “Getting to Zero”: preventing invasive Candida infections and eliminating infection-related mortality and morbidity in extremely preterm infants. Early Hum Dev 2012; 88 (Suppl. 02) S45-S49
    CrossrefPubMedSearch in Google Scholar
  • 9 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
    CrossrefPubMedSearch in Google Scholar
  • 10 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 (2) 172-179
    CrossrefPubMedSearch in Google Scholar
  • 11 Manzoni P, Stolfi I, Pugni L , et al; Italian Task Force for the Study and Prevention of Neonatal Fungal Infections; Italian Society of Neonatology. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. N Engl J Med 2007; 356 (24) 2483-2495
    CrossrefPubMedSearch in Google Scholar
  • 12 Kaufman DA, Manzoni P. Strategies to prevent invasive candidal infection in extremely preterm infants. Clin Perinatol 2010; 37 (3) 611-628
    CrossrefPubMedSearch in Google Scholar
  • 13 Martin A, Pappas A, Lulic-Botica M, Natarajan G. Impact of 'targeted' fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?. J Perinatol 2012; 32 (1) 21-26
    CrossrefPubMedSearch in Google Scholar
  • 14 Aydemir C, Oguz SS, Dizdar EA , et al. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Arch Dis Child Fetal Neonatal Ed 2011; 96 (3) F164-F168
    CrossrefPubMedSearch in Google Scholar
  • 15 Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 1993; 17 (2) 103-109
    CrossrefPubMedSearch in Google Scholar
  • 16 Hsieh E, Smith PB, Jacqz-Aigrain E , et al. Neonatal fungal infections: when to treat?. Early Hum Dev 2012; 88 (Suppl. 02) S6-S10
    CrossrefPubMedSearch in Google Scholar
  • 17 Austin N, McGuire W. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cochrane Database Syst Rev 2013; 4: CD003850
    PubMedSearch in Google Scholar
  • 18 Adams-Chapman I, Bann CM, Das A , et al; Eunice Kennedy Shriver National Institutes of Child Health and Human Development Neonatal Research Network. Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. J Pediatr 2013; 163 (4) 961-967 , e3
    CrossrefPubMedSearch in Google Scholar
  • 19 Uko S, Soghier LM, Vega M , et al. Targeted short-term fluconazole prophylaxis among very low birth weight and extremely low birth weight infants. Pediatrics 2006; 117 (4) 1243-1252
    CrossrefPubMedSearch in Google Scholar
  • 20 Bertini G, Perugi S, Dani C, Filippi L, Pratesi S, Rubaltelli FF. Fluconazole prophylaxis prevents invasive fungal infection in high-risk, very low birth weight infants. J Pediatr 2005; 147 (2) 162-165
    CrossrefPubMedSearch in Google Scholar
  • 21 Long SS, Stevenson DK. Reducing Candida infections during neonatal intensive care: management choices, infection control, and fluconazole prophylaxis. J Pediatr 2005; 147 (2) 135-141
    CrossrefPubMedSearch in Google Scholar
  • 22 McCrossan B, McHenry E, McCrossan BA, McHenry E, O'Neill F, Ong G, Sweet DG. Selective fluconazol prophylaxis in high-risk babies to reduce invasive fungal infection. Arch Dis Child Fetal Neonatal Ed 2007; 92: F454-F458
    CrossrefPubMedSearch in Google Scholar
  • 23 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 (2) 166-171
    CrossrefPubMedSearch in Google Scholar
  • 24 Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole-resistant Candida species. Pediatrics 2008; 121 (4) 703-710
    CrossrefPubMedSearch in Google Scholar
  • 25 Aziz M, Patel AL, Losavio J , et al. Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants. Pediatr Infect Dis J 2010; 29 (4) 352-356
    PubMedSearch in Google Scholar
  • 26 Benjamin Jr DK, Stoll BJ, Gantz MG , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics 2010; 126 (4) e865-e873
    CrossrefPubMedSearch in Google Scholar
  • 27 Howell AJ, Isaacs D, Halliday R ; Australasian Study Group For Neonatal Infections. Oral nystatin prophylaxis and neonatal fungal infections. Arch Dis Child Fetal Neonatal Ed 2009; 94 (6) F429-F433
    CrossrefPubMedSearch in Google Scholar
  • 28 Wynn JL, Tan S, Gantz MG , et al; NICHD Neonatal Research Network. Outcomes following candiduria in extremely low birth weight infants. Clin Infect Dis 2012; 54 (3) 331-339
    CrossrefPubMedSearch in Google Scholar