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. Trial Registration ClinicalTrials.gov Identifier: NCT02462590.

中文翻译：

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益生菌对危重患者呼吸机相关性肺炎的影响：一项随机临床试验。

重要性 对危重病期间微生物菌群失调的兴趣日益浓厚，这引发了对益生菌修饰微生物组的治疗潜力的质疑。之前在该人群中进行的随机试验表明，益生菌可以减少感染，尤其是呼吸机相关性肺炎 (VAP)，尽管也有益生菌相关感染的报道。目的评价鼠李糖乳杆菌GG对重症监护病房（ICU）预防VAP、额外感染和其他临床重要结果的作用。设计、设置和参与者 在加拿大、美国和沙特阿拉伯的 44 个 ICU 中进行的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 月共有 2653 名患者入组（最终随访，2020 年 10 月）。干预措施 ICU 每天两次肠内鼠李糖乳杆菌 GG（1 × 1010 菌落形成单位）（n = 1321）或安慰剂（n = 1332）。主要结果和措施 主要结果是通过重复盲法中央裁决确定的 VAP。次要结局是其他 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。结果 在 2653 名随机患者中（平均年龄 59.8 岁 [SD]，16.5 岁），2650 名（99.9%）完成了试验（平均年龄，59.8 岁 [SD]，16.5 岁；1063 名女性 [40.1%]，平均急性生理学和慢性健康评估 II 评分为 22.0 (SD, 7.8) 并接受研究产品的中位时间为 9 天 (IQR, 5-15 天)。在接受益生菌的 1318 名患者中，有 289 名 (21.9%) 与 284 名患者发生 VAP 1332 个控件 (21. 3%；风险比 [HR], 1.03 (95% CI, 0.87-1.22; P = .73, 绝对差异, 0.6%, 95% CI, -2.5% 至 3.7%)。包括其他 ICU 获得性感染、腹泻、抗菌药物使用、死亡率或住院时间在内的 20 项预设次要结局均未显示出显着差异。接受益生菌的 15 名患者 (1.1%) 与对照组中的 1 名 (0.1%) 患者在无菌部位或非无菌部位的唯一或主要微生物发生鼠李糖乳杆菌的不良事件（比值比，14.02；95% CI，1.79 -109.58；P < .001)。结论和相关性 在需要机械通气的危重患者中，与安慰剂相比，给予益生菌鼠李糖 GG 后，在发生呼吸机相关性肺炎方面没有显着差异。这些发现不支持在危重患者中使用鼠李糖乳杆菌 GG。试验注册 ClinicalTrials.gov 标识符：NCT02462590。