Clinical Pearls & Morning Reports
Freedman et al. conducted the Pediatric Emergency Research Canada (PERC) Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) trial to evaluate the effectiveness of probiotics in children 3 to 48 months of age who present to the emergency department with acute gastroenteritis. They hypothesized that the percentage of children with moderate-to-severe gastroenteritis (defined according to a validated severity score) within 14 days after enrollment would be significantly lower among those who received probiotics than among those who received placebo. Read the latest NEJM Original Article here.
Q: Do prior studies support the use of probiotics for intestinal infection?
A: Consumers increasingly take probiotics to treat intestinal infections, and 5 of 12 leading guidelines endorse the use of probiotics. Most studies of probiotics with results that have been published have had methodologic limitations and small sample sizes, have included limited investigations of causative pathogens, and have not reported adverse events. Numerous individual symptoms have been used as outcomes, but evaluations that incorporate both the duration and frequency of both diarrhea and vomiting are lacking. Given the distressing symptoms of gastroenteritis and the lack of benefit of probiotics shown in one North American study that enrolled children who received care in the emergency department, the role of probiotics in outpatient management of acute gastroenteritis in children warrants clarification.
Q: How is moderate-to-severe gastroenteritis defined?
A: In the trial by Freedman et al., the primary outcome was the occurrence of moderate-to-severe gastroenteritis, which was defined according to a total modified Vesikari scale symptom score of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease). The score was based on symptoms during the follow-up period and was calculated at the day 14 follow-up. The modified Vesikari scale quantifies severity over a broad range of symptoms and interventions, has been designed for outpatients, and was validated at most of the participating hospitals. The 14-day timeline was used to capture relationships between the use of probiotics and differences from placebo in the percentages of children who had prolonged diarrhea.
A: In the trial by Freedman et al., the authors found that a twice-daily, 5-day course of 4.0×109 colony-forming units of a combined Lactobacillus rhamnosus and L. helveticus probiotic did not prevent the development of moderate-to-severe gastroenteritis within 14 days after enrollment in young children who had had symptoms of gastroenteritis for up to 72 hours and had been brought for care in the emergency department. The percentage of participants who had a modified Vesikari score of 9 or higher after enrollment was similar between the groups (26.1% in the probiotic group [108 of 414 participants] and 24.7% in the placebo group [102 of 413 participants]); difference, 1.4 percentage points; 95% confidence interval, −4.5 to 7.3; P=0.65). No significant difference was observed in the percentage of participants with a modified Vesikari score of 9 or higher in any of the subgroups defined a priori. There was no evidence of benefit of probiotics according to the pathogen identified.
A: There were no significant differences between the probiotic group and the placebo group in the median duration of diarrhea or vomiting, the percentages of participants with unscheduled visits to a health care provider, and the percentage of adverse events reported.