加拿大麦克马斯特大学Deborah Cook团队联合多伦多大学Jennie Johnstone团队研究了益生菌对危重患者呼吸机相关性肺炎的影响。这一研究成果于2021年9月21日发表在《美国医学会杂志》上。

随着人们对危重疾病中微生物生态失调的日益关注，用益生菌修饰微生物组的治疗潜力被提上日程。此前在该人群中的随机试验表明，尽管益生菌相关感染也有报道，但益生菌可减少感染，特别是呼吸机相关肺炎（VAP）。

为了评价鼠李糖乳杆菌GG在重症监护病房（ICU）预防VAP、获得性感染和其他临床重要结局方面的作用，研究组在加拿大、美国和沙特阿拉伯的44个ICU中进行了一项随机安慰剂对照试验，纳入预计需要机械通气至少72小时的成年人。2013年10月至2019年3月，共登记了2653名患者（最终随访，2020年10月）。

将其随机分组，其中1321例患者在ICU内每日两次肠内L-鼠李糖GG给药，1332例接受安慰剂治疗。主要结局为双盲中央判定的VAP。次要结局为其他ICU获得性感染，包括艰难梭菌感染、腹泻、抗菌药物使用、ICU和住院时间以及死亡率。

2653名患者的平均年龄为59.8岁，2650名（99.9%）完成了试验，40.1%为女性，平均急性生理学和慢性健康评估II得分为22.0分，接受研究产品的中位时间为9天。1318名接受益生菌治疗的患者中有289名（21.9%）出现VAP，1332名对照组中有284名（21.3%），组间差异不显著。

两组间20项预先确定的次要结局，包括其他ICU获得性感染、腹泻、抗菌药物使用、死亡率或住院时间等，均无显著差异。益生菌治疗组中有15名（1.1%）患者在无菌环境或非无菌环境的单一或主要生物体发生了鼠李糖不良事件，显著高于对照组中的1名（0.1%）。

研究结果表明，在需要机械通气的危重病患者中，与安慰剂相比，给予益生菌L鼠李糖GG不会导致呼吸机相关肺炎的风险显著下降。该发现不支持在危重病人中使用鼠李糖乳GG。

附：英文原文

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

Author: Jennie Johnstone, Maureen Meade, Franois 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, Franois 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, Franois Marquis, Patrick Archambault, Kosar Khwaja, Arnold Kristof, James Kutsogiannis, Ryan Zarychanski, Bojan Paunovic, Brenda Reeve, Franois 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, Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) Investigators and the Canadian Critical Care Trials Group, Christine Wallace, Gita Sobhi, Jennie Johnstone, Franois Lauzier, Deborah Cook, Erick Duan, Joanna Dionne, Bram Rochwerg, John Centoanti, Simon Oczkowski, Daphne Lamarche, Michael Surette, Dawn Bowdish

Issue&Volume: 2021/09/21

Abstract:

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.

DOI: 10.1001/jama.2021.13355

Source: https://jamanetwork.com/journals/jama/article-abstract/2784358