Oral Nystatin Prophylaxis for the Prevention of Fungal Colonization in Very Low Birth Weight Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abdulrahman Al-Matary 1, Lina Almahmoud 2, Raneem Masmoum 3, Sultan Alenezi 4, Salem Aldhafiri 4, Abdullah Almutairi 5, Hussain Alatram 6, Athbi Alenzi 6, Mohammed Alajm 7, Ali Artam Alajmi 7, Hadil Alkahmous 8, Fulwah A Alangari 3, Abdulrahman AlAnzi 9, Salihah Ghazwani 10, Ahmed Abu-Zaid 11

Affiliations

doi: 10.7759/cureus.28345

Abstract

We conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the prophylactic role of oral nystatin in the prevention of fungal colonization in very low birth weight (VLBW) infants compared with placebo or no treatment intervention. From inception until June 2022, we screened four major databases for pertinent RCTs and examined their risk of bias. The main outcomes were the rate of fungal colonization, rate of invasive fungal infection, rate of mortality, mean length of stay in the neonatal intensive care unit (NICU), and mean duration of antibiotic treatment. We summarized data as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI), using the fixed-effects model. Five RCTs met our inclusion criteria. One RCT was evaluated as having "high risk," one RCT was evaluated as having "some concerns," and three RCTs were evaluated as having "low risk" of bias. Compared with the control group, oral nystatin prophylaxis was correlated with substantial decrease in the frequency of fungal colonization (n=4 RCTs, RR=0.34, 95% CI {0.24, 0.48}, p<0.0001), the rate of invasive fungal infection (n=4 RCTs, RR=0.15, 95% CI {0.12, 0.19}, p<0.0001), and the mean duration of antibiotic treatment (n=3 RCTs, MD=-2.79 days, 95% CI {-5.01, -0.56}, p=0.01). However, there was no significant difference between both groups regarding the rate of mortality (n=4 RCTs, RR=0.87, 95% CI {0.64, 1.18}, p=0.37) and mean length of stay in NICU (n=3 RCTs, MD=-2.85 days, 95% CI {-6.52, 0.82}, p=0.13). In conclusion, among VLBW infants, the prophylactic use of oral nystatin was correlated with favorable antifungal benefits compared with placebo or no treatment intervention.

Keywords: fungal colonization; fungal infection; low birth weight; meta-analysis; nystatin.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of literature search. CENTRAL: Cochrane Central Register of Controlled Trials

Figure 1. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of literature search. CENTRAL: Cochrane Central Register of Controlled Trials

Figure 2. Summary of the risk of bias of the included randomized controlled trials.

Figure 2. Summary of the risk of bias of the included randomized controlled trials.

Figure 3. Meta-analysis of the rate of fungal colonization.

Figure 3. Meta-analysis of the rate of fungal colonization.

Figure 4. Meta-analysis of the rate of invasive fungal infection.

Figure 4. Meta-analysis of the rate of invasive fungal infection.

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References

  1.  
    1. Not just little adults: candidemia epidemiology, molecular characterization, and antifungal susceptibility in neonatal and pediatric patients. Blyth CC, Chen SC, Slavin MA, et al. Pediatrics. 2009;123:1360–1368. - PubMed
  2.  
    1. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Stoll BJ, Hansen N, Fanaroff AA, et al. Pediatrics. 2002;110:285–291. - PubMed
  3.  
    1. Epidemiological features of nosocomial candidaemia in neonates, infants and children: a multicentre study in Iran. Ahangarkani F, Shokohi T, Rezai MS, et al. Mycoses. 2020;63:382–394. - PubMed
  4.  
    1. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Clin Infect Dis. 2004;39:309–317. - PubMed
  5.  
    1. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, Higgins RD. JAMA. 2004;292:2357–2365. - PubMed
  6.  
    1. Oral nystatin versus intravenous fluconazole as neonatal antifungal prophylaxis: non-inferiority trial. Mersal A, Alzahrani I, Azzouz M, et al. J Clin Neonatol. 2013;2:88–92. - PMC - PubMed
  7.  
    1. Oral nystatin prophylaxis to prevent invasive candidiasis in neonatal intensive care unit. Ozturk MA, Gunes T, Koklu E, Cetin N, Koc N. Mycoses. 2006;49:484–492. - PubMed
  8.  
    1. Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants. Austin N, Cleminson J, Darlow BA, McGuire W. Cochrane Database Syst Rev. 2015;2015 - PMC - PubMed
  9.  
    1. Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants. Cleminson J, Austin N, McGuire W. Cochrane Database Syst Rev. 2015;2015 - PMC - PubMed
  10.  
    1. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Moher D, Liberati A, Tetzlaff J, Altman DG. PLoS Med. 2009;6 - PMC - PubMed
  11.  
    1. London, England: Cochrane; 2022. Cochrane Handbook for Systematic Reviews of Interventions.
  12.  
    1. RoB 2: a revised tool for assessing risk of bias in randomised trials. Sterne JA, Savović J, Page MJ, et al. BMJ. 2019;366 - PubMed
  13.  
    1. Bias in meta-analysis detected by a simple, graphical test. Egger M, Davey Smith G, Schneider M, Minder C. BMJ. 1997;315:629–634. - PMC - PubMed
  14.  
    1. Measuring inconsistency in meta-analyses. Higgins JP, Thompson SG, Deeks JJ, Altman DG. BMJ. 2003;327:557–560. - PMC - PubMed
  15.  
    1. Prophylactic oral nystatin and fungal infections in very-low-birthweight infants. Sims ME, Yoo Y, You H, Salminen C, Walther FJ. Am J Perinatol. 1988;5:33–36. - PubMed
  16.  
    1. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Aydemir C, Oguz SS, Dizdar EA, et al. Arch Dis Child Fetal Neonatal Ed. 2011;96:164–168. - PubMed
  17.  
    1. Oral nystatin prophylaxis to prevent systemic fungal infection in very low birth weight preterm infants: a randomized controlled trial. Rundjan L, Wahyuningsih R, Oeswadi CA, Marsogi M, Purnamasari A. BMC Pediatr. 2020;20 - PMC - PubMed
  18.  
    1. Effectiveness of oral nystatin prophylaxis in the prevention of Candida colonization in very low birth weight preterm neonates; a randomized controlled trial. Marzban A, Aghdam MK, Ahadi S. https://ijn.mums.ac.ir/article_20231_8b10979d1f51d336501b4ec22608389c.pdf Iran J Neonatol. 2022;13:91–97.
  19.  
    1. Clinical use of oral nystatin in the prevention of systemic candidosis in patients at particular risk. Schäfer-Korting M, Blechschmidt J, Korting HC. Mycoses. 1996;39:329–339. - PubMed
  20.  
    1. Challenging issues in neonatal candidiasis. Kaufman DA. Curr Med Res Opin. 2010;26:1769–1778. - PubMed
  21.  
    1. Prophylactic oral nystatin for preterm babies under 33 weeks' gestation decreases fungal colonisation and invasive fungaemia. Ganesan K, Harigopal S, Neal T, Yoxall CW. Arch Dis Child Fetal Neonatal Ed. 2009;94:275–278. - PubMed
  22.  
    1. Oral nystatin prophylaxis and neonatal fungal infections. Howell A, Isaacs D, Halliday R. Arch Dis Child Fetal Neonatal Ed. 2009;94:429–433. - PubMed
  23.  
    1. Chemoprophylaxis of neonatal fungal infections in very low birthweight infants: efficacy and safety of fluconazole and nystatin. Blyth CC, Barzi F, Hale K, Isaacs D. J Paediatr Child Health. 2012;48:846–851. - PubMed
  24.  
    1. The global burden of fungal diseases. Vallabhaneni S, Mody RK, Walker T, Chiller T. Infect Dis Clin North Am. 2016;30:1–11. - PubMed
  25.  
    1. Global and multi-national prevalence of fungal diseases-estimate precision. Bongomin F, Gago S, Oladele RO, Denning DW. J Fungi (Basel) 2017;3 - PMC - PubMed

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