关键词: Acute myeloid leukemia antibiotic resistance gene fecal microbiota transplantation hematopoietic cell transplantation

Mesh : Humans Fecal Microbiota Transplantation / methods Anti-Bacterial Agents / pharmacology therapeutic use Gastrointestinal Microbiome / genetics Treatment Outcome Drug Resistance, Microbial Feces

来  源:   DOI:10.1080/19490976.2024.2327442   PDF(Pubmed)

Abstract:
In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.
摘要:
在小系列中,第三方粪便微生物移植(FMT)已成功地从临床相关抗生素抗性基因(ARGs)对肠道进行脱色.关于FMT对大型ARG面板的短期和长期影响知之甚少。我们分析了接受异基因造血细胞移植或接受抗白血病诱导化疗47例ARG的100例患者中FMT随机安慰剂对照试验的226例治疗前后粪便样本。这些患者的抗生素暴露量很大,并且多药耐药生物的定植发生率很高。每位患者的样本长达9个月,允许我们描述FMT对ARG的短期和长期影响,而随机设计允许我们区分自发变化与FMT效应。我们发现了一个整体的双峰模式。在第一阶段(FMT后几天到几周),ARGs的低水平转移主要与共生健康供体微生物群相关。此阶段之后是对新ARG的长期抗性,因为在FMT之后形成了具有定殖抗性的稳定群落。这些发现的临床意义可能取决于上下文,需要进一步研究。在癌症和强化治疗的背景下,长期的ARG去定植可以转化为较少的下游感染.
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