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. Fluconazole prophylaxis against fungal colonization and invasive fungal infection in very low birth weight infants. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight. A multicenter, randomized trial of prophylactic fluconazole in preterm neonates. Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: a prospective, randomized, open-label, placebo-controlled pilot study. Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant.
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. 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. 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 tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants.
                We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients.
                Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented.
                Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance. 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. This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates.
                This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality.
                Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality.
                L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.
                Copyright 2010. Published by EM Inc USA. Candidal infections are an important cause of morbidity and mortality in the very low birth weight (VLBW) infant. Current intervention focuses on treatment once candidal septicemia is either suspected or diagnosed. Studies have suggested that colonization with candidal species is an important risk factor for subsequent infection.
                To determine whether prophylactic fluconazole for the first 28 days of life results in a decreased incidence of candidal colonization in the VLBW infant.
                Prospective, randomized, controlled, intention-to-treat design comparing prophylaxis with fluconazole versus placebo for the first 28 days of life.
                A tertiary level intensive care nursery in a major teaching hospital in Charleston, South Carolina.
                One hundred three infants with a birth weight of <1500 g, either inborn or outborn, who were admitted to the intensive care nursery between January 1998 and February 1999.
                Infants were enrolled within 72 hours of life with rectal cultures performed on the day of randomization (DOR), as well as day of life (DOL) 7, 14, and 28. Those infants with a birth weight of <1250 g had additional cultures on DOL 35, 49, and 56. Cultures were plated on selective media for isolation of candidal organisms. Infants were randomized to receive either fluconazole (6 mg/kg) or placebo on the DOR. Subsequent doses were given every 72 hours until DOL 7 and then every 24 hours until DOL 28. Medication was given either intravenously or by feeding tube once the infant had been gavage feeding for a 48-hour period without feeding intolerance. Aspartate aminotransferase and alanine aminotransferase levels were obtained on DOR and DOL 7, 14, and 28 to assess for fluconazole toxicity. The minimal inhibitory concentration to fluconazole was determined for all positive cultures to assess the development of resistance.
                The infants who received fluconazole (n = 53) and placebo (n = 50) had no statistical difference in the major risk factors known to increase the chances of candidal septicemia in the VLBW infant. Rectal colonization by candidal species was detected in 8 of the 53 fluconazole-treated patients (15.1%) and in 23 of the 50 infants treated with placebo (46%). Fluconazole significantly reduced rectal colonization from DOL 14 through DOL 56 in all infants with a birth weight of <1250 g, and from DOL 14 through DOL 56 in all infants with a birth weight of 1250 to 1500 g. Alanine aminotransferase levels were higher in the fluconazole versus the placebo-treated group on DOL 14 (18.1 IU/L vs 15 IU/L), but no clinically significant abnormalities were observed. Candida albicans was the most common species isolated. There was no increase in species of Candida noted for their intrinsic resistance to fluconazole, and there was no statistically significant difference in the minimal inhibitory concentrations to fluconazole for all C albicans isolates in either group at any period.
                Prophylactic administration of fluconazole to the VLBW infant for the first 28 days of life is safe and results in a decreased risk of rectal colonization by candidal species. Larger studies to determine the effect of prophylaxis on candidal septicemia and development of resistance in such a selective high-risk group are warranted before initiation of routine prophylaxis.fluconazole, very low birth weight infant, prophylaxis, candidal sepsis, sensitivities to fluconazole.
Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very low birth weight infants. This finding should be interpreted and applied cautiously since the incidence of invasive fungal infection was very high in the control groups of most of the included trials. Meta-analysis does not demonstrate a statistically significant effect on mortality. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.