Division of Gastroenterology and Hepatology, Weill Department of Medicine, Weill Cornell Medicine, New York, New York.
Hospitalist Medicine Section, Division of General Internal Medicine, Department of Medicine, University of Colorado, Denver, Colorado.
Gastroenterology. 2017 Jun;152(8):1889-1900.e9. doi: 10.1053/j.gastro.2017.02.003. Epub 2017 Feb 10.
BACKGROUND & AIMS: Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice.
We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality.
We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high.
In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.
系统评价已经为益生菌预防艰难梭菌感染（CDI）的疗效提供了证据，但指南并不推荐使用益生菌预防 CDI。我们进行了一项更新的系统评价，以帮助指导临床实践。
我们在 MEDLINE、EMBASE、国际益生菌和益生元杂志以及 Cochrane 图书馆数据库中搜索了评估住院接受抗生素治疗的成年人使用益生菌和 CDI 的随机对照试验。两名评审员独立提取数据，并评估了偏倚风险和证据的总体质量。主要和次要结局分别为 CDI 的发生率和不良事件。二次分析检查了益生菌种类、剂量、时间、配方、持续时间和研究质量的影响。
我们分析了来自 19 项已发表研究的数据，共纳入 6261 名受试者。益生菌组 CDI 的发生率为 1.6%（54/3277），低于对照组的 3.9%（115/2984）（P<0.001）。益生菌使用者 CDI 的汇总相对风险为 0.42（95%置信区间，0.30-0.57；I=0.0%）。荟萃回归分析表明，如果益生菌在接近第一剂抗生素时使用，其效果更为显著，而每延迟一天开始使用益生菌，疗效就会降低（P=0.04）；与抗生素开始后使用相比，在抗生素开始后 2 天内使用益生菌可显著降低 CDI 的风险（相对风险，0.32；95%置信区间，0.22-0.48；I=0%）（相对风险，0.70；95%置信区间，0.40-1.23；I=0%）（P=0.02）。使用益生菌的患者不良事件风险没有增加。证据的总体质量很高。
在一项系统评价中，我们通过荟萃回归分析发现，在住院成人中，更接近抗生素首剂使用益生菌可使 CDI 的风险降低>50%。未来的研究应侧重于最佳益生菌剂量、种类和配方。
PROSPERO CRD42015016395。
