A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. Prophylactic oral nystatin and fungal infections in very-low-birthweight infants. Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants. Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study.
Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.
                During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.
                Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect.
                Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).
                Copyright 2007 Massachusetts Medical Society. 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. Fungal infections are common cause of morbidity and mortality in very low birth weight Infants
                To evaluate the efficacy of prophylactic Fluconazole in preventing fungal colonization and invasive fungal infection in VLBW infants.
                Prospective, randomized, double blind placebo controlled clinical trial.
                Tertiary level Neonatal intensive care unit.
                120 preterm infants with birth Weight < 1500 g.
                Infants were randomly assigned during first three days to receive either Fluconazole or placebo till 28 days or less if, discharged or died earlier. Weekly surveillance cultures from groin, oropharynx, rectum and blood were collected in all patients. Fungal isolates were typed based on standard microbiologic techniques. Liver enzymes were monitored.
                Baseline risk factors for fungal infection in Fluconazole and Placebo groups were similar. Fungal colonization was seen in 30 infants (50%) in the placebo group and 11 infants (19%) in the Fluconazole group (P <0.001). Fungal colonization at rectum, groin and oropharynx was less in fluconazole groups. Fluconazole group showed significantly lower colonizations with Candida albicans but not with C. glabrata. Invasive infection was seen in 15 (25%) infants in Placebo group and 16 (26.7%) infants in Fluconazole group (P = 0.835). Various non-albicans Candida were responsible for 96.8% cases of invasive fungal infection (Candida glabrata 71%, C. parapsilosis 14.7% and C. tropicalis 9.6%). No significant hepatotoxicity was noticed during Fluconazole therapy.
                Prophylactic fluconazole during the first four weeks of life is effective in reducing fungal colonization but not invasive infection in VLBW 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. Colonization by Candida species is the most important predictor of the development of invasive fungal disease in preterm neonates, and the enteric reservoir is a major site of colonization. We evaluated the effectiveness of an orally supplemented probiotic (Lactobacillus casei subspecies rhamnosus; Dicoflor [Dicofarm spa]; 6 x 10(9) cfu/day) in the prevention of gastrointestinal colonization by Candida species in preterm, very low birth weight (i.e., < 1500-g) neonates during their stay in a neonatal intensive care unit.
                Over a 12-month period, a prospective, randomized, blind, clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit. During the first 3 days of life, the neonates were randomly assigned to receive either an oral probiotic added to human (maternal or pooled donors') milk (group A) or human milk alone (group B) for 6 weeks or until discharge from the NICU, if the neonate was discharged before 6 weeks. On a weekly basis, specimens obtained from various sites (i.e., oropharyngeal, stool, gastric aspirate, and rectal specimens) were collected from all patients for surveillance culture, to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract.
                The incidence of fungal enteric colonization (with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site) was significantly lower in group A than in group B (23.1% vs. 48.8%; relative risk, 0.315 [95% confidence interval, 0.120-0.826]; P = .01). The numbers of fungal isolates obtained from each neonate (P = .005) and from each colonized patient (P = .005) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001-1500 g. There were no changes in the relative proportions of the different Candida strains. No adverse effects potentially associated with the probiotic were recorded.
                Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by Candida species among very low birth weight neonates.
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.