Effectiveness of Oral Nystatin Prophylaxis in the Prevention of Candida Colonization in Very Low Birth Weight Preterm Neonates; a Randomized Controlled Trial

Document Type : Original Article


1 Department of Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran

2 Department of Pediatric, Zanjan University of Medical Sciences, Zanjan, Iran


Background: The present study aimed to assess the effectiveness of oral nystatin as antifungal prophylaxis in the prevention of fungal colonization in premature neonates admitted to neonatal intensive care units (NICUs).
Methods: This randomized controlled trial was conducted on 106 neonates admitted to NICUs in the first 72 h of their life with gestational age, gestational age of fewer than 32 weeks, and birth weight of less than 1500 g. The neonates were randomly assigned to two groups: the case group (received nystatin, n=53) and the control group (did not receive nystatin, n=53). After one week, swabs were prepared from the oral and rectal mucosa of the subjects for smear and fungal culture.
Results: The results obtained from the culture revealed that nystatin prophylaxis significantly decreased the colonization of Candida in premature neonates (P=0.03). Moreover, nystatin prophylaxis was significantly associated with Candida colonization in preterm infants with the following characteristics: a gestational age of 28-32 weeks (0 (0.0%) vs. 5 (10.9%)) (P= 0.05), very low birth weight (VLBW) infants (0 (0.0%) vs. 8 (16.0%))  (P=0.007), neonates born via normal vaginal delivery (NVD) (1 (11.1%) vs. 8 (72.7%)) (P=0.01), infants born after preterm rupture of the membrane (PROM) (1 (10.0%) vs. 6 (75.0%)) (P=0.01), and neonates taking broad-spectrum antibiotics (1 (3.7%) vs. 7 (26.9%)) (P=0.02).
Conclusion: The present study demonstrated that nystatin prophylaxis might be considered an effective drug in the prevention of Candida colonization and might lower the risk of SFIs; nonetheless, it had no significant effect on extremely low birth weight (ELBW) neonates. Since nystatin is safe, well-tolerated, affordable, and effective, further studies are required to confirm it as a therapeutic option for ELBW newborns with Candida infections.


  1. Calley JL, Warris A. Recognition and diagnosis of invasive fungal infections in neonates. J Infect. 2017;74:S108–13.
  2. Ahangarkani F, Shokohi T, Rezai MS, Ilkit M, Mahmoodi Nesheli H, Karami H, et al. Epidemiological features of nosocomial candidaemia in neonates, infants and children: a multicentre study in Iran. Mycoses. 2020;63(4):382–94.
  3. Howell A, Isaacs D, Halliday R, Infections ASGFN. Oral nystatin prophylaxis and neonatal fungal infections. Arch Dis Childhood-Fetal Neonatal Ed. 2009;94(6):F429–33.
  4. Isaacs D. Fungal prophylaxis in very low birth weight neonates: nystatin, fluconazole or nothing? Curr Opin Infect Dis. 2008;21(3):246–50.
  5. Chapman RL. Prevention and treatment of Candida infections in neonates. In: Seminars in perinatology. Elsevier; 2007. p. 39–46.
  6. Ting JY, Roberts A, Synnes A, Canning R, Bodani J, Monterossa L, et al. Invasive fungal infections in neonates in Canada: epidemiology and outcomes. Pediatr Infect Dis J. 2018;37(11):1154–9.
  7. Manzoni P, Jacqz-Aigrain E, Rizzollo S, Franco C, Stronati M, Mostert M, et al. Antifungal prophylaxis in neonates. Early Hum Dev. 2011;87:S59–60.
  8. Zaini F, Mehbod AS, Emami M. Comprehensive medical mycology. Tehran: Tehran University publications; 2013.
  9. Ozturk MA, Gunes T, Koklu E, Cetin N, Koc N. Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit. Mycoses. 2006;49(6):484–92.
  10. Aydemir C, Oguz SS, Dizdar EA, Akar M, Sarikabadayi YU, Saygan S, 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 Childhood-Fetal Neonatal Ed. 2011;96(3):F164–8.
  11. Rundjan L, Wahyuningsih R, Oeswadi CA, Marsogi M, Purnamasari A. Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial. BMC Pediatr. 2020;20:1–9.
  12. Ganesan K, Harigopal S, Neal T, Yoxall CW. Prophylactic oral nystatin for preterm babies under 33 weeks’ gestation decreases fungal colonisation and invasive fungaemia. Arch Dis Childhood-Fetal Neonatal Ed. 2009;94(4):F275–8.
  13. Islam S, Khan KA, Nahar N, Rahman M, Kabir A. Oral Nystatin: An effective prophylaxis for fungal infection in preterm babies in a tertiary level hospital. J Pediatr Neonatal Care. 2016;5(9):726769.
  14. Manzoni P, Farina D, Galletto P, Leonessa M, Priolo C, Arisio R, et al. Type and number of sites colonized by fungi and risk of progression to invasive fungal infection in preterm neonates in neonatal intensive care unit. J Perinat Med. 2007;35(3):220-6.
  15. 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):1660–6.