Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Oral nystatin prophylaxis to prevent invasive candidiasis in Neonatal Intensive Care Unit. Prophylactic oral nystatin and fungal infections in very-low-birthweight infants. Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection.
We compared the efficacy and safety of fluconazole and nystatin oral suspensions for the prevention of systemic fungal infection (SFI) in very low birthweight infants. A prospective, randomized clinical trial was conducted over a 15-month period, from May 1997 through September 1998, in 80 preterm infants with birthweights <1500 g. The infants were randomly assigned to receive oral fluconazole or nystatin, beginning within the first week of life. Prophylaxis was continued until full oral feedings were attained. Blood and urine cultures were obtained at enrollment and then weekly thereafter. Thirty-eight infants were randomly assigned to receive oral fluconazole (group I), and 42 infants were assigned to receive nystatin (group II). Birthweight, gestational age, and risk factors for fungal colonization and SFI at the time of randomization and during the hospital course were similar in both groups. SFI developed in two infants (5.3%) in group I and six infants (14.3%) in group II. The difference between these two rates was not statistically significant (relative risk, 0.37; 95% confidence interval, 0.08 to 1.72). There were no deaths in group I and six deaths in group II (P = 0.03). Two infants died of neonatal sepsis, and four deaths were related to necrotizing enterocolitis and/or spontaneous intestinal perforation. No deaths were due to SFI. Enrollment was halted before completion and the study did not attain adequate power to detect a hypothesized drop in SFI rate from 15 to 5%. Although the results cannot justify any conclusion about the relative efficacy of fluconazole versus nystatin in prevention of SFI, the significantly higher mortality rate in the nystatin group raises questions about the relative safety of this medication.
                Thieme Medical Publishers. Invasive fungal infections are a major cause of morbidity and mortality in preterm infants. The authors conducted the first prospective, randomised controlled trial of nystatin compared with fluconazole for the prevention of fungal colonisation and invasive fungal infection in very low birth weight (VLBW) neonates.
                During a 12-month period, all VLBW neonates were assigned randomly to receive nystatin (1 ml suspension, 100 000 U/ml, every 8 h), fluconazole (3 mg/kg body weight, every third day) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). The authors performed weekly surveillance cultures and systemic fungal susceptibility testing.
                During the study period, 278 infants (fluconazole group, n=93; nystatin group, n=94; control group, n=91) weighing <1500 g at birth were admitted. There were no differences in birth weight, gestation, gender or risk factors for fungal infection among the groups. Fungal colonisation occurred in 11.7% of the nystatin group and 10.8% of the fluconazole group, as compared with 42.9% of the control group. The incidence of invasive fungal infection was 4.3% in the nystatin group and 3.2% in the fluconazole group, as compared with 16.5% in the control group. There were no differences in fungal colonisation and invasive fungal infection between the nystatin and fluconazole groups.
                Prophylactic nystatin and fluconazole reduce the incidence of colonisation and invasive fungal infection in VLBW neonates. The authors believe that nystatin is an alternative to fluconazole, because nystatin is safe, inexpensive, well tolerated and effective. The use of oral nystatin to prevent fungal colonisation and infection in neonates in the Neonatal Intensive Care Unit (NICU) is still an open question and not yet recommended as a standard of care. To determine whether prophylactic oral nystatin results in a decreased incidence of invasive candidiasis in the newborn infants, a total of 3991 infants were divided randomly into two groups. Group A infants (n = 1995), only those neonates who were identified as yeast carriers (oral moniliasis) were treated with oral nystatin. Group B infants, all neonates who were admitted to the unit received oral nystatin, was routinely administered three times a day. Group A was divided into groups A1 and A2 (who were treated only if identified as yeast carriers). Urine and rectal cultures were taken on admission and then weekly thereafter. There were 215 (14.2%), 27 (5.6%) and 36 (1.8%) patients positive for invasive candidiasis in groups A1, A2 and B respectively. Oral nystatin prophylaxis significantly reduced the invasive candidiasis (P = 0.004) in extremely low-birth weight (ELBW) and very low-birth weight (VLBW) infants. Prophylactic administration of oral nystatine to the ELBW and VLBW infants results in a decreased risk of invasive candidiasis. Prevention of systemic fungal infection in the very-low-birthweight infant is important since it is associated with a high morbidity and mortality. To determine if oral nystatin administration could prevent fungal colonization and infection, we evaluated 67 preterm infants with birthweights less than 1250 gm. Thirty-three infants received 1 ml (100,000 units/ml) of nystatin inside the mouth every 8 hours until 1 week after extubation. Oropharyngeal, rectal, blood, and urine cultures were obtained on the 1st day of life and weekly. Endotracheal cultures were obtained three times a week from intubated infants. Four (12%) of the 33 nystatin-treated infants had positive cultures, two (6%) developed systemic infection. The control group consisted of 34 infants, 15 (44%) had positive fungal cultures and 11 (32%) developed systemic infection. Fungi isolated were Candida species and Torulopsis glabrata. Colonized infants were dependent on the respirator (P less than 0.001), had indwelling catheters (P less than 0.01), and received antibiotics (P less than 0.05) for a longer period than infants free from fungi and their mortality was significantly higher (P less than 0.05). We conclude that prophylactic administration of oral nystatin reduces fungal colonization and infection in very-low-birthweight infants. Prior rectal colonization with fungi may be an important risk factor for development of systemic fungal infection in the neonate. This placebo-controlled study evaluated the benefits of miconazole oral gel in the prevention of fungal rectal colonization and systemic infection in high risk neonates admitted to the Neonatal Intensive Care Unit. Repeated oral application of miconazole gel reduced the overall prevalence of postnatally acquired rectal colonization; a yeast was grown in 19.5% of the weekly rectal swabs in the miconazole-treated group compared with 36.2% in the control group (69 of 354 vs. 146 of 403, P < 0.0001). There was no reduction in the incidence of systemic fungal infection in the two groups although the overall incidence of the infection was low in both groups, at 2.0% vs. 2.6% (6 of 298 vs. 8 of 302, P not significant). No relationship was shown between prior rectal colonization and subsequent systemic fungal infections in either of the two groups. This study does not support the use of prophylactic miconazole oral gel for the prevention of neonatal systemic fungal infections.
The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.