Cibulkova Ivana, Rehorova Veronika, Soukupova Hana, Waldauf Petr, Cahova Monika, Manak Jan, Matejovic Martin, Duska Frantisek
Division of Gastroenterology, Department of Internal Medicine, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
The Third Faculty of Medicine, Charles University, Prague, Czech Republic.
PLoS One. 2024 Dec 27;19(12):e0310180. doi: 10.1371/journal.pone.0310180. eCollection 2024.
Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.
Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota.
Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims.
www.clinicaltrials.gov (NCT05430269).
重症患者使用抗生素会导致肠道菌群失调，常表现为抗生素相关性腹泻。粪便微生物群移植可恢复肠道微生物群，并可能使腹泻更快得到缓解。
在这项前瞻性、多中心、随机对照试验中，我们将招募36例患有抗生素相关性腹泻的重症患者。我们将排除正在发生败血症、需要全身使用抗生素的患者，或近期接受过肠道手术的患者，或因任何其他原因无法进行粪便微生物群移植（FMT）的患者。随机分组比例为1:1。对照组患者将接受基于口服蒙脱石的标准治疗。干预组患者除接受标准治疗外，还将通过直肠管接受粪便微生物群移植，移植制剂由7份解冻的等分试样（50毫升）混合而成，这些等分试样取自7名健康非亲属供体的新鲜粪便，并在深度冷冻隔离3至12个月。主要结局是治疗失败，定义为未进行干预或随机分组后第7天腹泻仍持续。次要结局包括全身炎症反应、不良事件等安全指标，以及28天内腹泻复发情况。探索性结局聚焦于肠道屏障功能和肠道微生物群组成。
粪便微生物群移植对非重症复发性艰难梭菌感染患者的菌群失调有效，推测其对重症患者菌群失调症状同样有效是合理的。此外，动物实验和观察数据表明还有其他益处，如减少多重耐药菌定植以及改善肠道屏障和免疫功能。与亲属的粪便不同，非亲属供体的冷冻粪便在需要时可立即获取，亲属粪便需要长时间检测。使用多个供体可使移植微生物群的多样性最大化。尽管如此，在脆弱的重症患者中，粪便微生物群移植可能导致细菌易位和不可预见的并发症。从越来越多的病例系列来看，其在重症患者中的非标签使用正在增加，迫切需要客观评估其疗效和安全性，本试验旨在解决这一问题。
