A multispecies probiotic failed to prevent children’s antibiotic-associated diarrhea (AAD) in a randomized trial when examined under the strictest definition, but the researchers still saw a potential benefit, citing a lower overall risk for diarrhea of any kind in the probiotic group.
In an intention-to-treat analysis of 313 pediatric patients, the probiotic (Ecologic AAD 612) did not significantly reduce the risk for AAD versus placebo when AAD was defined as three or more loose/watery stools per day from Clostridioides difficile (C. difficile) or another unexplained source, reported Jan Łukasik, MD, of the Medical University of Warsaw in Poland, and colleagues from the Multispecies Probiotic in AAD Study Group.
As such, the trial missed its primary endpoint, with 14.6% of those in the probiotic group meeting this stringent AAD definition versus 18.1% of those assigned placebo (relative risk [RR] 0.81, 95% CI 0.49-1.33), according to the findings.
“However, we found a beneficial effect of the formulation on the overall risk of diarrhea during and 7 days after antibiotic therapy,” the group wrote in JAMA Pediatrics. “The latter outcome corresponds well with the standard approach to AAD in clinical practice. Therefore, the use of the studied probiotic may be considered for diarrhea prevention during antibiotic treatment in children.”
Regardless of etiology, 20.9% of the probiotic patients experienced diarrhea versus 32.3% with placebo (RR 0.65, 95% CI 0.44-0.94), with a number need to benefit of 9. And fewer patients in the probiotic group required the use of intravenous rehydration because of diarrhea as well (none vs 3.2%, respectively).
Reached for comment, Bhaskar Gurram, MD, of the University of Texas Southwestern Medical Center in Dallas, told MedPage Today that he would need to see if giving this particular probiotic would be cost effective.
“I typically use specific probiotics (Saccharomyces boulardii and Lactobacillus GG) to prevent antibiotic associated diarrhea,” said Gurram, who was not involved in this study. “Unless I see another trial involving this combination probiotic for infectious diarrhea, I will not change my practice.”
AAD can be a common complication of antibiotic treatment, as changes in the gut microbiota can lead to an overgrowth of pathogens such as C. difficile, Łukasik’s group noted. While administering live microorganisms or probiotics has been shown to provide moderate protection against AAD in children, many of the prior studies incorporated a limited number of species.
The current trial is the largest to incorporate more than three species, the group noted, with Ecologic AAD 612 consisting of Bifidobacterium lactis W51, Bifidobacterium bifidum W23, Lactobacillus acidophilus W37 and W55, Lactocaseibacillus paracasei W20, Lactoplantibacillus plantarum W62, Ligilactobacillus salivarius W24, and Lactocaseibacillus rhamnosus W71.
Łukasik and colleagues enrolled 350 patients within 24 hours of initiating oral or intravenous broad-spectrum systemic antibiotics from pediatric clinical and outpatient wards of three Dutch hospitals (n=148) and two Polish hospitals (n=202). From February 2018 to May 2021, patients were randomized 1:1 to receive a total dose of 10 billion colony-forming units of the daily multispecies probiotic, or placebo, for the duration of antibiotic treatment, and then for 7 more days afterward.
The quadruple-blinded trial included patients ages 3 months to 18 years. Exclusion criteria were use of antibiotics or probiotics within the past 4 weeks, or receipt of antidiarrheal drugs, proton pump inhibitors, or laxatives within the past 2 weeks, among others.
Mean age was 50 months, 55% were boys, and over three-fourths were inpatients. Most were receiving antibiotics for lower respiratory infection (31%), upper respiratory infection (29%), or urinary tract infection (17%). Aminopenicillin was most commonly prescribed (35%). Average treatment duration was 10 days, and the average hospital stay was 5 days.
Of the 83 patients who developed diarrhea, 10 were positive for rotavirus, three tested positive for norovirus, one for adenovirus, and one for Salmonella enterica.
On logistic regression, AAD was associated with younger age alone, while any diarrhea was linked with younger age, receiving amoxicillin with clavulanic acid, and being allocated to the placebo group. No differences were seen among adverse events between the two study groups.
The authors acknowledged limitations to the data, including the short follow-up duration and potential for the misclassification of outcomes. Patients were not tested for pathogens at baseline and could have been in an incubation period. Also, a large number of patients were lost to follow-up (15% of the Polish patients and 4% of the Dutch patients).
Funding for the probiotics and placebo used in this study was provided by Winclove Probiotics B.V. in The Netherlands.
Łukasik and coauthors disclosed relationships with Winclove Probiotics B.V.