• 一项多中心随机对照试验,2653名使用呼吸机的危重病人分2组,经肠内途径补充鼠李糖乳杆菌GG(LGG)或安慰剂;
  • 益生菌组和安慰剂组分别有21.9%和21.3%的患者发生呼吸机相关肺炎,组间差异不显著;
  • 其他次要终点在两组间也无显著差异(ICU获得性感染、腹泻、抗生素使用、死亡率、住院时长等);
  • 两组分别有1.1%和0.1%的患者发生不良事件(从血液等样本中分离出乳杆菌属细菌,多数鉴定为LGG),提示危重病人使用LGG有感染风险。
JAMA [IF:157.335]

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients A Randomized Clinical Trial



2021-09-21, Article

Abstract & Authors:展开

Importance : Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported.
Objective : To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU).
Design, Setting, and Participants : Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020).
Interventions : Enteral L rhamnosus GG (1 × 1010 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU.
Main Outcomes and Measures : The primary outcome was VAP 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.
Results : Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .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 vs 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 < .001).
Conclusions and Relevance : Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients.

First Authors:
Jennie Johnstone

Correspondence Authors:
Deborah Cook

All Authors:
Jennie Johnstone,Maureen Meade,François Lauzier,John Marshall,Erick Duan,Joanna Dionne,Yaseen M Arabi,Diane Heels-Ansdell,Lehana Thabane,Daphnee Lamarche,Michael Surette,Nicole Zytaruk,Sangeeta Mehta,Peter Dodek,Lauralyn McIntyre,Shane English,Bram Rochwerg,Tim Karachi,William Henderson,Gordon Wood,Daniel Ovakim,Margaret Herridge,John Granton,M Elizabeth Wilcox,Alberto Goffi,Henry T Stelfox,Daniel Niven,John Muscedere,François Lamontagne,Frédérick D'Aragon,Charles St-Arnaud,Ian Ball,Dave Nagpal,Martin Girard,Pierre Aslanian,Emmanuel Charbonney,David Williamson,Wendy Sligl,Jan Friedrich,Neill K Adhikari,François Marquis,Patrick Archambault,Kosar Khwaja,Arnold Kristof,James Kutsogiannis,Ryan Zarychanski,Bojan Paunovic,Brenda Reeve,François Lellouche,Paul Hosek,Jennifer Tsang,Alexandra Binnie,Sébastien Trop,Osama Loubani,Richard Hall,Robert Cirone,Steve Reynolds,Paul Lysecki,Eyal Golan,Rodrigo Cartin-Ceba,Robert Taylor,Deborah Cook