Keating Julie A, Xu Tinghui, Graham Mary Beth, Ramesh Mayur, Khanna Sahil, Dixon Jonah, Kates Ashley, Haight Kendra, Zhao Jiwei, Saddler Christopher, Safdar Nasia
Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison.
William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
JAMA Netw Open. 2025 Jul 1;8(7):e2517834. doi: 10.1001/jamanetworkopen.2025.17834.
Systemic antibiotic use for patients with a non-Clostridioides difficile infection (CDI) is a major risk factor for recurrent CDI. Increasing use of oral vancomycin for secondary prophylaxis against recurrent CDI in this context has uncertain efficacy.
To evaluate whether oral vancomycin prophylaxis compared with placebo is effective against recurrent CDI during and 8 weeks after the end of study treatment.
DESIGN, SETTING, AND PARTICIPANTS: This phase 2, placebo-controlled, double-blind randomized clinical trial was conducted in 4 large health systems across the upper Midwest US. Adults who had completed treatment for CDI within the past 180 days and were taking a systemic antibiotic for a non-CDI indication were enrolled between May 21, 2018, and March 30, 2023, and followed up for 8 weeks after the end of study treatment.
Participants were randomized 1:1 to 125 mg of oral vancomycin or placebo once daily during antibiotic use for a non-CDI plus 5 days following cessation of those antibiotics.
The primary outcome was recurrent CDI incidence during treatment and the 8-week follow-up period. The secondary outcome was vancomycin-resistant Enterococcus carriage in stool.
Among 81 randomized participants (median age, 59 years [IQR, 50-67 years]), all were included in the primary as-randomized analysis (39 in the vancomycin group; 42 in the placebo group). Sixty patients (74.1%) completed 8-week follow-up and were included in the secondary as-completed treatment analysis (31 in the vancomycin group; 29 in the placebo group). Recurrent CDI occurred in 17 of 39 participants in the oral vancomycin group (43.6%) and 24 of 42 in the placebo group (57.1%; absolute difference in percentage, -13.5% [95% CI, -35.1% to 8.0%]). Adverse events occurred in 27 of 39 participants in the oral vancomycin group (69.2%) and 27 of 42 in the placebo group (64.3%). Vancomycin-resistant Enterococcus carriage was found in 15 of 30 patients in the oral vancomycin group (50.0%) and 6 of 25 in the placebo group (24.0%) (P = .048) 8 weeks after treatment.
In this randomized clinical trial, the incidence of recurrent CDI was lower (though did not reach significance) in participants taking oral vancomycin compared with those taking placebo. Because the study was underpowered, it was unable to reveal firm conclusions about the efficacy (or lack thereof) of vancomycin prophylaxis with respect to recurrent CDI.
ClinicalTrials.gov Identifier: NCT03462459.
对于非艰难梭菌感染（CDI）患者使用全身性抗生素是复发性CDI的主要危险因素。在这种情况下，增加口服万古霉素用于复发性CDI的二级预防，其疗效尚不确定。
评估与安慰剂相比，口服万古霉素预防在研究治疗期间及结束后8周内对复发性CDI是否有效。
设计、设置和参与者：这项2期、安慰剂对照、双盲随机临床试验在美国中西部上游的4个大型医疗系统中进行。在2018年5月21日至2023年3月30日期间，招募了在过去180天内完成CDI治疗且因非CDI指征正在服用全身性抗生素的成年人，并在研究治疗结束后随访8周。
参与者按1:1随机分为每天一次口服125mg万古霉素或安慰剂，在因非CDI使用抗生素期间及这些抗生素停用后5天服用。
主要结局是治疗期间及8周随访期内复发性CDI的发生率。次要结局是粪便中耐万古霉素肠球菌的携带情况。
在81名随机分组的参与者中（中位年龄59岁[四分位间距，50 - 67岁]），所有参与者均纳入主要随机分析（万古霉素组39人；安慰剂组42人）。60名患者（74.1%）完成了8周随访，并纳入次要完成治疗分析（万古霉素组31人；安慰剂组29人）。口服万古霉素组39名参与者中有17人（43.6%）发生复发性CDI，安慰剂组42名参与者中有24人（57.1%）发生复发性CDI（百分比绝对差异为 -13.5%[95%置信区间，-35.1%至8.0%]）。口服万古霉素组39名参与者中有27人（69.2%）发生不良事件，安慰剂组42名参与者中有27人（64.3%）发生不良事件。治疗8周后，口服万古霉素组30名患者中有15人（50.0%）检测到耐万古霉素肠球菌携带，安慰剂组25名患者中有6人（24.0%）检测到（P = 0.048）。
在这项随机临床试验中，与服用安慰剂的参与者相比，服用口服万古霉素的参与者复发性CDI的发生率较低（尽管未达到显著水平）。由于该研究的效能不足，无法就万古霉素预防复发性CDI的疗效（或缺乏疗效）得出确凿结论。
ClinicalTrials.gov标识符：NCT03462459。
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