A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. Randomised controlled trial of prophylactic fluconazole versus nystatin for the prevention of fungal colonisation and invasive fungal infection in very low birth weight infants. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. Comparison of fluconazole and nystatin oral suspensions for prophylaxis of systemic fungal infection in very low birthweight infants. Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants. Fluconazole vs. amphotericin B for the treatment of neonatal fungal septicemia: a prospective randomized trial. Prophylactic oral nystatin and fungal infections in very-low-birthweight infants. Staphylococcal and streptococcal colonization of the newborn infant: effect of antiseptic cord care. Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders.
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. 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. Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants.
                We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients.
                The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented.
                Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g. 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. 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. Fungal septicemia is a devastating disease in the neonate, especially in the low birth weight preterm infant who is especially vulnerable to disseminated fungal sepsis. The objective of this study was to compare the efficacy, safety and overall convenience of fluconazole vs. amphotericin B for the treatment of disseminated fungal sepsis in neonates.
                A prospective, randomized, collaborative study conducted at two South African neonatal units.
                Twenty-four infants with proven fungal septicemia were treated from June, 1992, to June, 1993. Twelve received fluconazole, 11 received amphotericin B and 1 was excluded. Assessment of hepatic, renal and hematologic functions were performed before, during and after treatment. The two groups were comparable at the time of enrollment into the study.
                Infants receiving amphotericin B had significantly higher values of total and direct bilirubin and alkaline phosphatase values at the end of treatment, while the fluconazole group showed a significant increase in the platelet count. The cumulative total numbers of days receiving intravenous therapy for the administration of antifungal drugs were 57 for the fluconazole group and 162 for the amphotericin group; no central lines were needed in the fluconazole group, whereas 3 babies given amphotericin B had central catheters for a cumulative total of 27 days. The case fatality rate was 33% in the fluconazole group and 45% in the amphotericin B group; there was still proof of fungal septicemia at the time of death in 1 patient given amphotericin B and 2 given fluconazole.
                Fluconazole showed fewer side effects than amphotericin B and was more convenient to use. 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. A randomized controlled study was undertaken to compare the effectiveness of three umbilical cord treatment regimens in controlling neonatal bacterial colonization. The three regimens studied included castile soap, triple dye, and silver sulfadiazine. The triple dye and silver sulfadiazine application inhibited bacterial colonization. Staphylococcal colonization was inhibited by both treatment regimens but most effectively by triple dye. Group B streptococcal colonization was inhibited most effectively by silver sulfadiazine while triple dye application to the umbilicus promoted colonization with this microorganism. Silver sulfadiazine was more effective in controlling colonization with Gram-negative microorganisms. The occurrence of invasive fungal infection (IFIs) in a pediatric hematology/oncology unit after renovation of the ventilation system, and initiating routine azole antifungal prophylaxis was monitored. In addition, the value of serial screening for Aspergillus galactomannan (GM) for diagnosing invasive aspergillosis was assessed.
                A total of 98 consecutive high-risk pediatric patients were prospectively surveyed for signs of IFI and weekly monitored for serum GM. The data was not made available to treating physicians.
                Only 2 patients had proven and 27 possible IFI based on the European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions. The incidence of proven IFI was 1/31 (3.2%) in the allogeneic stem cell transplant (SCT) (Aspergillus spp), 0/26 in the autologous SCT, and 1/60 (1.6%) in the induction therapy group (C. krusei). GM was detected at least in one tested sample in 12/98 patients (12.2%), in five patients in two or more sequential samples. In the latter group, IFI was proven in one patient and could not be excluded in the others. Four of the five patients belonged to the 31 allogeneic and one to the 26 autologous SCT patients. In patients with only one positive GM test none developed signs of IFI and only one received empirical amphotericin B.
                With the currently used preventative and prophylactic measures, IFI is uncommon in children with high-risk for infection. Regular screening for GM could be useful among allogeneic SCT patients and two positive samples should prompt further investigative procedures and pre-emptive antifungal therapy.
                (c) 2006 Wiley-Liss, Inc.
There are insufficient data to inform practice. Large randomised controlled trials are required to compare antifungal drugs, drug preparations or drug combinations for treating newborn infants with invasive fungal infection.