Study does not support probiotic use in certain critically ill patients
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Critically ill patients who required mechanical ventilation and received the probiotic Lactobacillus rhamnosus GG were as likely to develop ventilator-associated pneumonia as those who received placebo, a randomized clinical trial showed.
“Among critically ill patients, randomized trials suggest that probiotics reduce infection rates by 20% and may decrease the risk of ventilator-associated pneumonia by 25% to 30%,” Jennie Johnstone, MD, PhD, an associate professor of medical microbiology in the department of laboratory medicine and pathobiology at the University of Toronto, and colleagues wrote in JAMA. “Current guidelines suggest probiotic use for selected medical and surgical ICU patients for whom trials have documented safety and benefit.”
According to a previous review, ventilator-associated pneumonia may account for as many as 47% of ICU-acquired infections, making it the second-most common nosocomial infection in the United States.
In the new trial, Johnstone and colleagues analyzed data from 2,650 patients (mean age, 59.8 years; 40.1% women) who were hospitalized in either an American, Canadian or Saudi Arabian ICU. The mean Acute Physiology and Chronic Health Evaluation II score of all patients was 22 (out of a maximum of 71) at baseline and all were predicted to require mechanical ventilation for at least 72 hours. The patients were randomly assigned in an approximate 1:1 ratio to receive either enteral L. rhamnosus GG (1 × 1010 colony-forming units) or placebo twice daily for a median of 9 days.
Johnstone and colleagues reported that ventilator-associated pneumonia developed in 21.9% of patients who received probiotics and 21.3% of those who received placebo (HR = 1.03; 95% CI, 0.87-1.22; absolute difference = 0.6%; 95% CI, –2.5% to 3.7%). There were no significant differences between the two groups regarding other ICU-acquired infections, diarrhea, antimicrobial use, mortality or length of stay and more than a dozen other clinical outcomes.
Fifteen patients who were administered L. rhamnosus GG experienced an adverse event compared with 1 patient who received placebo (OR = 14.02; 95% CI, 1.79-109.58). Two patients in the probiotic group experienced a serious adverse event, and both died, the researchers reported.
Johnstone and colleagues noted several limitations to their study.
“Results may have differed using an alternate dose, genus, species or strain or if studied in specialized populations such as patients who experienced trauma or were of low surgical risk with lower antimicrobial exposure or lower infectious risk,” they wrote. “Second, it was not possible to examine pulmonary microbiota over time or between groups, or probiotic gastrointestinal colonization in this international trial. Third, there are inherent limitations of each [ventilator-associated pneumonia] definition and no universal reference standard; however, our analyses were strengthened by protocolized data collection and use of several definitions.”
Regardless, they concluded that their findings “do not support the use of [L. rhamnosus GG] for prevention of ventilator-associated pneumonia in critically ill patients requiring mechanical ventilation.”
References:
Grap MJ, et al. J Emerg Med. 2012;doi:10.1016/j.jemermed.2010.05.042.
Johnstone J, et al. JAMA. 2021;doi:10.1001/jama.2021.13355.
Morrow LE, et al. Am J Respir Crit Care Med. 2010;doi:10.1164/rccm.200912-1853OC.
Perspective
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Todd W. Rice, MD, MSc
In general, critical care nutrition guidelines are ambivalent regarding probiotic use in critically ill patients. This ambivalence derives from the lack of high quality, randomized trials evaluating probiotic use in this population.
This study by Johnstone and colleagues from the Canadian Critical Care Trials group provides some of that much needed rigorous evaluation and high-quality evidence. Administration of the commonly prescribed probiotic Lactobacillus rhamnosus GG did not reduce the risk of ventilator-associated pneumonia or improve other clinical outcomes in their multicenter, international, blinded, placebo-controlled randomized trial.
While results are overall disappointing, it is exciting to see such meticulous research in critical care nutrition, and specifically probiotics, from a premiere critical care clinical trials group. This is the exact high-quality science that will better advance the field and help us better understand the role for nutritional supplements, probiotics and other critical care nutritional interventions moving forward.
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