Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Intestinal Domination and the Risk of Bacteremia in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
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DOI：
10.1093/cid/cis580
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发表时间：
2012-10-01
影响因子：
11.8
通讯作者：
Pamer, Eric G.
中科院分区：
文献类型：
--
作者：
Taur, Ying;Xavier, Joao B.;Pamer, Eric G.
背景菌血症是异基因造血干细胞移植（allo-HSCT）的常见并发症。目前尚不清楚allo-HSCT期间肠道微生物群的变化是否有助于菌血症的发展。我们检查了接受allo-HSCT的患者的微生物群，并将微生物变化与菌血症风险相关联。从94例接受allo-HSCT的患者中纵向收集粪便标本，从移植前到移植后35天。通过细菌16 S核糖体RNA基因的V1-V3区域的454焦磷酸测序来表征肠道微生物群。微生物多样性的估计分组序列到操作分类单位和计算香农多样性指数。使用核糖体数据库项目分类器获得系统发育分类。评估了微生物群与临床预测因素和结果的相关性。在allo-HSCT期间，患者的多样性降低，肠道细菌种群发生明显变化。肠道优势，定义为占领至少30%的微生物群由一个单一的优势细菌类群，经常发生。常见的优势菌包括肠球菌、链球菌和各种变形菌。肠球菌统治增加了3倍，甲硝唑管理，而氟喹诺酮管理的变形菌减少了10倍。作为预后的预测因子，肠球菌占优势使万古霉素耐药肠球菌菌血症的风险增加9倍，变形菌占优势使革兰氏阴性杆菌菌血症的风险增加5倍。在allo-HSCT期间，肠道植物群的多样性和稳定性被破坏，导致与随后的菌血症相关的细菌占优势。粪便微生物群的评估确定了allo-HCST期间血流感染风险最高的患者。
Background. Bacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia.Methods. Fecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated.Results. During allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold.Conclusions. During allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.