Add-on L. reuteri mitigates diarrhoea risk in children on antibiotics

Adding the probiotic Limosilactobacillus reuteri (L. reuteri) DSM 17938 to antibiotic therapy significantly reduced the incidence of antibiotic-associated diarrhoea (AAD) in children with acute otitis media or acute bacterial sinusitis in the PEARL study presented at ESPGHAN 2023.

“Antibiotics are the cornerstone of therapy for serious bacterial infections … However, AAD has been observed to be one of the most significant side effects of antibiotic therapy,” said Dr Ener Cagri Dinleyici from the Department of Pediatrics at Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey. 

Dinleyici noted that according to recent ESPGHAN guidelines, the use of probiotics, particularly Saccharomyces boulardii or Lacticaseibacillus rhamnosus GG, has shown some beneficial effects in preventing AAD.

In the current study, Dinleyici and his team sought to determine the beneficial effect of adding L. reuteri DSM 17938 to antibiotic therapy on the prevention of AAD in children.

A total of 654 children (aged 6 months to 10 years) with acute otitis media or acute bacterial sinusitis were treated with amoxicillin-clavulanic acid 50–90 mg/kg/day twice daily for 10–14 days. In addition, participants were given L. reuteri DSM 17938 (5 drops=10⁸ cfu) twice daily for 10–14 days, or additional 7 days after antibiotic cessation, (n=330) or placebo for 10–14 or 21 days (n=324). All patients were followed up until 56 days. [ESPGHAN 2023, abstract N-O042]

Incidence of AAD

During the first 14 days of intervention, patients who received L. reuteri had a significantly lower incidence of AAD, defined as ≥3 loose or watery stools per day for ≥48 hours, than those on placebo (7.8 percent vs 16.6 percent; relative risk [RR], 0.47; p<0.001).

After antibiotic cessation, significantly fewer children experienced AAD in the L. reuteri group at 21 days (8.7 percent vs 17.9 percent; RR, 0.49; p<0.001) and 56 days (9.0 percent vs 19.7 percent; RR, 0.46; p<0.001) than those in the placebo group.

“Our hypothesis was that if we continued to use probiotics after discontinuing antibiotics, we might prevent more cases,” said Dinleyici. However, when the number of days of probiotic use was assessed, the incidence of AAD was similar between the L. reuteri and placebo groups across all time points (7.1 percent vs 8.0 percent [14 days], 9.5 percent vs 8.0 percent [21 days], and 10.1 percent vs 8.6 percent [56 days]; p>0.05 for all).

Duration of diarrhoea

Among patients with AAD, the duration of diarrhoea was significantly longer in the placebo group than the L. reuteri group (mean 3.29 vs 0.84 days; p<0.01).

This was consistent with results seen in prior studies showing that L. reuteri reduced the duration of diarrhoea in children, Dinleyici noted.

In terms of safety, L. reuteri DSM 17983 was well-tolerated, and there were no dropouts related to L. reuteri use in the study, said Dinleyici.

“Overall, L. reuteri DSM 17938 significantly reduced the incidence of AAD during the first 14 days of antibiotic use, and also during the 56-day follow-up period in children receiving antibiotics due to acute otitis media or sinusitis,” said Dinleyici.

“Restoration with probiotics might be a resolution, but we should also keep in mind the need for appropriate use of antibiotics in order to prevent antibiotic-associated dysbiosis,” he noted.