Treatment of critically ill patients on mechanical ventilation with the probiotic Lactobacillus rhamnosus GG failed to reduce the risk for developing ventilator-associated pneumonia in the large, multicenter PROSPECT randomized trial.
In the study, which included patients treated in 44 ICUs in Canada, the United States, and Saudi Arabia, no significant difference in ventilator assisted pneumonia incidence was reported among patients treated with probiotics compared with placebo (21.9% versus 21.3%).
The findings differ from several smaller trials that suggested a benefit for probiotic therapy in this setting, and they “do not support the use” of L rhamnosus GG for the prevention of ventilator-associated pneumonia or other clinically important outcomes in critically ill patients, wrote researcher Deborah Cook, MD, of St. Joseph’s Healthcare, Ontario, Canada, and PROSPECT colleagues.
Study findings were published online Sept. 21 in the Journal of the American Medical Association.
Cook and colleagues noted that probiotics have emerged “as a biologically plausible strategy to treat or prevent a wide range of infectious, inflammatory and autoimmune conditions.”
“Postulated mechanisms of benefit for a broad spectrum of diseases include enhanced gut barrier function, competitive inhibition of pathogenic bacteria, and modulation of the host inflammatory response,” they added.
A 2016 meta-analysis of 30 randomized trials involving a total of 2,972 patients found probiotic therapy to be associated with a 20% reduction in infection and a 25% to 30% reduction in ventilator-assisted pneumonia among critically ill patients.
Current guidelines suggest probiotic use in selected medical and surgical ICU patients for whom trials have documented safety and benefit.
The PROSPECT trial was conducted to further explore the use of probiotic therapy as a strategy for the prevention of ventilator-associated pneumonia.
The study included 2,653 patients (mean age, 59.8 years [SD], 16.5 years) receiving treatment in an ICU and predicted to require mechanical ventilation for at least 24 hours.
Enrollment occurred between October 2013 and March 2019, with final follow-up occurring in October 2020.
The primary study outcome was ventilator-associated pneumonia determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU, and hospital length of stay and mortality.
Almost all (99.9%) enrolled patients completed the trial and the mean patient age was 59.8 years, SD 16.5 years. A total of 40% of the enrolled patients were female, and the cohort had a mean APACHE II score of 22.0 (SD, 7.8).
The probiotic was given for a median of 9 days (IQR, 5-15 days) and ventilator-associated pneumonia developed in 289 of 1,318 patients (21.9%) receiving probiotics versus 284 of 1,332 controls (21.3%; HR, 1.03; 95% CI, 0.87-1.22; P =0.73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%).
None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay, showed a significant difference.
Fifteen patients (1.1%) receiving probiotics versus 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P<0.001).
Study strengths included the large number of patients, high protocol adherence and absence of loss to follow-up.
“Probiotic capsule integrity was independently documented, aligning with calls for larger rigorous trials of probiotics in a range of human conditions,” the researchers wrote.
Study limitations included the use of a single probiotic and a single dosage, leading the research team to conclude that “results may have differed using an alternative 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.”
The PROSPECT investigators wrote that the trial findings differ from the meta-analyses of previous smaller, predominantly single-center studies, which suggested decreased rates of ventilator-associated pneumonia associated with probiotic treatment of critically ill patients.
They noted, however, that the increased risk of adverse events among PROSPECT patients receiving probiotics aligns with a recent report of L rhamnosus GG bacteremia in critically ill children prescribed this probiotic.
“These results indicate that although critically ill patients exhibit loss of commensal microbiota, overgrowth of potential pathogens and thus highly perturbed microbial communities, probiotics may not improve clinically important outcomes associated with dysbiosis in this setting,” they wrote. “Rigorous probiotics trials with neutral results enhance clinical decision-making, inform resource allocation, and ensure balanced systematic reviews and guidelines.”
Treatment of critically ill patients requiring mechanical mechanical ventilation with the probiotic Lactobacillus rhamnosus GG failed to reduce the risk for developing ventilator-associated pneumonia in a large, multicenter PROSPECT randomized trial.
No significant difference in ventilator assisted pneumonia incidence was reported among patients treated with probiotics compared with placebo (21.9% versus 21.3%).
Salynn Boyles, Contributing Writer, BreakingMED™
This study was funded by the Canadian Institute for Health Research, Canadian Frailty Network, Physician Services Incorporated, Hamilton Academic Health Sciences Organization and others.
Cat ID: 124
Topic ID: 79,124,730,124,192,152,925