Probiotic administration and the incidence of nosocomial infection in pediatric intensive care: A randomized placebo-controlled trial

Objective: To evaluate the efficacy of probiotics in reducing the rates of nosocomial infection in pediatric intensive care. Design: Randomized, double-blind, placebo-controlled trial. Setting: A 16-bed pediatric intensive care unit in a university-affiliated children's hospital. Patients: Sixty-one pediatric patients were enrolled from April 2004 until December 2004. Screening of all patients admitted occurred on a daily basis. Patients were excluded if they had the following: evidence/suspicion of intestinal perforation, evidence/ suspicion of mechanical gastrointestinal obstruction, absolute neutrophil count <= 0.5 x 10(9) cells/L, judgment by the attending physician that unable to tolerate the enteral volume necessary for administration, use of a probiotic preparation at any time in the week before study entry, participation in another clinical trial, lack of parental presence, or lack of parental consent. Interventions: Patients were randomized to receive either one capsule of Lactobacillus rhamnosus strain GG (Culturelle, Con-Agra Foods, Omaha, NE) or placebo capsule of insulin once a day until discharge from the hospital. Results: Sixty-one patients were randomized: 31 in the treatment group and 30 on the placebo group. Three patients in the control group developed four infections. Six patients in the treatment group developed 11 infections. The relative risk of developing infection in the treatment group was 1.94 (confidence interval [CI], 0.53 to 7.04; p = .31). The mean number of infections in the treatment and control groups was 1.83 and 1.33, respectively, with a difference of 0.5 (p = .52). No serious adverse effects in the study population were noted. However, due to recent safety concerns regarding the administration of L. rhamnosus strain GG and a lack of benefit in this interim analysis, the study was terminated by the study investigators. Conclusions: The results of this preliminary investigation were unexpected but important in view of the increased use of probiotic preparations in medically fragile pediatric patients. In this randomized, placebo-controlled trial, L. rhamnosus strain GG was not shown to be effective in reducing the incidence of nosocomial infections. In fact, a statistically nonsignificant trend toward an increase in infection was seen (four vs. 11). Further studies with a larger patient population are needed to establish both safety and efficacy of probiotics in pediatric critical care.