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 over 2,500 mechanically ventilated patients, the 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 difference between groups was observed for a multitude of other secondary outcomes, including ICU mortality (21.2% vs. 22.2%, respectively), in-hospital mortality (27.5% vs. 28.6%), duration of ventilation (7 days), length of stay in hospital or intensive care (22 and 12 days, respectively, in the two groups), other infections acquired in intensive care, incidence of diarrhea or use of antimicrobials.
“These results do not support the use of L. rhamnosus GG for the prevention of ventilator-associated pneumonia or other clinically important findings 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 is not as surprising,” said Megan Conroy, MD, of the Wexner Medical Center at Ohio State University in Columbus. MedPage today. “We have no large-scale, quality evidence to suggest that probiotics play a role in routine intensive care care or in the prophylaxis of infections acquired in intensive care. “
Conroy, who was not involved in this study, said the current standard of care for the prevention of VAP “includes routine oral hygiene care, including the use of a product based on VAP. of chlorhexidine, keeping the head of the bed elevated by at least 30 degrees, eliminating secretions, minimizing sedation, maximizing arousal and mobility on a ventilator and, above all, limiting the duration as much as possible mechanical ventilation. “
For their study, Cook and colleagues randomized 2,653 ICU patients on 1: 1 mechanical ventilation to either L. rhamnosus GG (1 × 10ten colony forming units) twice daily or a placebo. Patients requiring mechanical ventilation for at least 3 days were recruited from 2013 to 2019 from 41 intensive care units in Canada, two in the United States and one in Saudi Arabia. Patients received the probiotic for a median of 9 days.
The average age of the patients was 60 years and about 40% were women. Average patient score on the Acute Physiology and Chronic Health Assessment II was 22 years old. At the start of the study, over 60% of participants were taking vasopressors or inotropics, 8% were undergoing kidney replacement therapy, and over 80% were taking antimicrobials. Over 70% had infection on admission and 60% had pneumonia.
The primary outcome measure was the incidence of VAP, defined as an invasive infection on the chest x-ray 2 days after ventilation, in addition to fever, hypothermia or an unusual number of white blood cells and the presence of purulent sputum.
No significant difference was observed in Clostridium difficile (It’s hard) infections, 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-analyzes of previous small, predominantly single-center studies suggesting decreased levels of VAP associated with probiotics during severe disease, including this strain,” wrote Cook and co-authors. “However, the conclusions of this trial are consistent with a trial showing no effect of a Lactobacillus acidophilus and Bifidobacterium preparation on It’s hard infection in older hospitalized patients receiving antibiotics.
The analysis had several limitations, the researchers acknowledged. Alternative dosing may have occurred due to varying probiotic strains, and it was not possible to assess lung microbiota and probiotic gastrointestinal colonization due to the nature of the study.
This study was funded by the Canadian Frailty Network, Canadian Institute for Health Research, Physician Services Incorporated, Academic Medical Organization of Southwestern Ontario, Hamilton Academic Health Sciences Organization, McMaster University, St. Joseph’s Healthcare Hamilton, and I- Health.
Cook has revealed that he holds a research chair for the Canadian Institutes of Health Research. The co-authors noted grants, awards and some relationship with industry.