Oral Nystatin Prophylaxis to Prevent Systemic Fungal Infection in Very Low Birth Weight Preterm Infants : A Randomized Controlled Trial

Abstract

Background Systemic fungal infection (SFI) is one of leading causes of morbidity and mortality in very low birth weight (VLBW) preterm infants. Because early diagnosis of SFI is challenging due to nonspecific manifestations, prophylaxis becomes crucial. This study aimed to assess effectiveness of oral nystatin as an antifungal prophylaxis to prevent SFI in VLBW preterm infants. Methods A prospective, open-labelled, randomized controlled trial was performed in a neonatal intensive care unit (NICU) of an academic hospital in Indonesia. Infants with a gestational age < 32 weeks and/or birth weight of < 1500 grams with risk factors of fungal infection were assessed for eligibility and randomized to either an intervention group (nystatin) or control group. The intervention group received 1 ml of oral nystatin three times a day, and the control group received a dose of 1ml of sterile water three times a day. The incidence of fungal colonization and SFI were observed and evaluated during the six-week study period. Overall, mortality rates and nystatin-related adverse drug reactions during the study period were also documented. Results A total of 95 patients were enrolled. The incidence of fungal colonization was lower among infants in nystatin group compared to those in control group (29.79% and 56.25%, respectively; relative risk 0.559; 95% confidence interval 0.357-0.899; p-value=0.009). There were five cases of SFI, all of which were found in the control group (p-value=0.056). There was no difference in overall mortality between the two groups. No adverse drug reactions were noted during the study period. Conclusions Nystatin is effective and safe as an antifungal prophylactic medication in reducing colonization rates in the study population. Whilst the use of nystatin showed a potential protective effect against SFI among VLBW preterm infants, there was no statistical significant difference in SFI rates between groups.

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

“…Figure 1 shows the PRISMA flow chart for our screening steps. Overall, five RCTs met our criteria and were included in the final analysis [7,[15][16][17][18]. A total of 1750 participants were enrolled in these studies (n=884 participants were allocated to nystatin group and n=866 participants were allocated to the control group).…”

“…The summary and baseline characteristics of the included studies are shown in Table 1 and Table 2, respectively. Figure 2 shows the risk of bias summary of the included studies [7,[15][16][17][18]. Three RCTs showed overall "low risk" of bias [7,16,17], one RCT revealed overall "some concerns/unclear risk" of bias [18], and one RCT revealed overall "high risk" of bias [14].…”

“…Figure 2 shows the risk of bias summary of the included studies [7,[15][16][17][18]. Three RCTs showed overall "low risk" of bias [7,16,17], one RCT revealed overall "some concerns/unclear risk" of bias [18], and one RCT revealed overall "high risk" of bias [14]. Sims et al study was evaluated in the randomization process domain as "high risk" because the allocation sequence was not concealed [15].…”

“…The overall effect size between nystatin arm and the control arm did not significantly differ between both arms (MD=-2.85 days, 95% CI {-6.52, 0.82}, p=0.13) (Figure 6) [15][16][17]. Three RCTs with 347 patients reported the mean duration of antibiotic treatment [15][16][17]. The overall effect size between nystatin arm and the control arm significantly favored nystatin arm (MD=-2.79 days, 95% CI {-5.01, -0.56}, p=0.01) (Figure 7) [15][16][17].…”

“…The overall effect size between nystatin arm and the control arm significantly favored nystatin arm (RR=0.15, 95% CI {0.11, 0.21}, p<0.0001) (Figure 4) [7,[15][16][17]. Four RCTs with 1644 patients reported the rate of mortality [7,[15][16][17]. The overall effect size between nystatin arm and the control arm did not significantly differ between both arms (RR=0.87, 95% CI {0.64, 1.18}, p=0.37) (Figure 5) [7,[15][16][17].…”