Probiotic Flops for Ventilator-Associated Pneumonia Prevention

For critically ill patients in the intensive care unit (ICU), administration of a probiotic failed to prevent ventilator-associated pneumonia (VAP), a multinational randomized trial showed.

In an analysis of more than 2,500 patients on mechanical ventilation, incidence of VAP was 21.9% in the group receiving a Lactobacillus rhamnosus GG (L. rhamnosus GG) probiotic and 21.3% in those assigned to placebo (HR 1.03, 95% CI 0.87-1.22, P=0.730), reported Deborah Cook, MD, MSc, of St. Joseph’s Healthcare in Hamilton, Ontario, and colleagues.

No between-group differences were observed for a host of other secondary outcomes as well, including ICU mortality (21.2% vs 22.2%, respectively), hospital mortality (27.5% vs 28.6%), time on ventilation (7 days), length of hospital or ICU stay (22 and 12 days, respectively, in both group), other ICU-acquired infections, diarrhea incidence, or antimicrobial use.

“These findings do not support the use of L. rhamnosus GG for prevention of ventilator-associated pneumonia or other clinically important outcomes in critically ill patients,” the group concluded in JAMA.

Adverse events or serious adverse events were more common in the probiotic group (15 vs 1 in the placebo group; OR 14.02, 95% CI 1.79-109.58).

“This study doesn’t come as much of a surprise,” Megan Conroy, MD, of the Ohio State University Wexner Medical Center in Columbus, told MedPage Today. “We don’t have any large-scale, quality evidence to suggest that probiotics have a role in routine ICU care or prophylaxis for any ICU-acquired infections.”

Conroy, who was not involved in this study, said that the current standard of care for preventing VAP “includes routine oral hygiene care, including the use of a chlorhexidine product, keeping the head of the bed elevated at least 30 degrees, removal of subglottic secretions, minimizing sedation, maximizing wakefulness as well as mobility while on the ventilator, and, importantly, limiting the duration of mechanical ventilation as best able.”

For their study, Cook and colleagues randomized 2,653 ICU patients on mechanical ventilation 1:1 to either enteral L. rhamnosus GG (1 × 10¹⁰ colony-forming units) twice daily or placebo. Patients expected to be on mechanical ventilation for at least 3 days were enrolled from 2013 to 2019 at 41 ICUs in Canada, two in the U.S., and one in Saudi Arabia. Patients received the probiotic for a median of 9 days.

Average patient age was 60 years and about 40% were women. Patients’ mean score on the Acute Physiology and Chronic Health Evaluation II was 22. At the start of the study, over 60% of participants were taking vasopressors or inotropes, 8% were on kidney replacement therapy, and over 80% were on antimicrobials. Over 70% had an infection at admission and 60% had pneumonia.

The primary outcome was incidence of VAP, defined as an infiltrating infection on chest x-ray at 2 days post-ventilation, in addition to a fever, hypothermia, or unusual white blood cell count, and presence of purulent sputum.

No significant difference was seen regarding Clostridium difficile (C. difficile) infections, at 2.4% in the probiotic group and 2.1% in the placebo group (OR 1.15, 95% CI 0.69-1.93, P=0.60). Overall, about 81% of patients developed diarrhea.

“These results differ from meta-analyses of previous small, predominantly single-center studies, suggesting decreased VAP rates associated with probiotics during critical illness, including this strain,” wrote Cook and coauthors. “However, findings from this trial do accord with a trial showing no effect of a Lactobacillus acidophilus and Bifidobacterium preparation on C. difficile infection in older hospitalized patients receiving antibiotics.”

The analysis had several limitations, the researchers acknowledged. Alternative dosing may have occurred due to variable probiotic strains, and pulmonary microbiota and probiotic gastrointestinal colonization were not possible to assess due to the nature of the study.