2-002 | Additional Comments | Previous Article | Next Article | List of Articles | Submit Comments | Index | FSN Home Page
Fluconazole Prophylaxis
Fluconazole for Prophylaxis Against Candidal Rectal Colonization in the Very Low Birth Weight Infant. Pediatrics 2001; 107: 293- 298.
One hundred and three infants with birth weights < 1500 gms were randomized to receive either fluconazole (6 mg/kg IV or OG q72h until DOL 7, then q24h until DOL 28) or placebo during the first 28 days of life. Rectal cultures were plated on selective media for isolation of candidal organisms on the day of randomization (DOR), and on days 7, 14, 28, and 56. Liver function tests were obtained on DOR, and on DOL 7, 14, and 28 to assess for fluconazole toxicity. The minimal inhibitory concentration concentration to fluconazole was determined for all positive cultures to assess the development of resistance. 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. Alanine aminotransferase were significantly higher in the fluconazole versus placebo-treated group on DOL 14 (18.1 IU/L versus 15 IU/L), but no clinically significant abnormalities were observed. There was no increase in species of Candida noted for their intrinsic resistance to fluconazole, and there was no statistically significant difference in the MIC to fluconazole for all C. albicans isolates in either group at any period.
Comment. While this study demonstrates a decrease in rectal colonization with Candida in VLBW infants using fluconazole prophylaxis, this is not the outcome variable of greatest interest to neonatal clinicians. The study was not designed to determine whether fluconazole prophylaxis would decrease the incidence of invasive Candidal disease in this population, and, in fact, no difference in the rate of invasive candidiasis was seen between the two groups. Furthermore, there are still concerns about the potential for developing resistant strains of Candida with widespread fluconazole use in our nurseries. While the authors did not notice any increase in fluconazole resistance in the Candida strains isolated during this study, they concede that the study was too short and the numbers too small to draw any real conclusions about the potential of selecting for fluconazole-resistant Candida strains. These concerns and others were addressed by Drs. Neely and Schreiber in a commentary published in the same issue of Pediatrics entitled : Fluconazole Prophylaxis in the VLBW Infant: Not ready for Prime Time.