PDF(Pubmed)
Abstract：
Carbapenem-resistant Enterobacteriaceae (CRE) pose a global health threat; however, there is still limited understanding of the risk factors and underlying mechanisms of CRE colonization in the gut microbiome. We conducted a matched case-control study involving 282 intensive care unit patients to analyze influencing covariates on CRE colonization. Subsequently, their effects on the gut microbiome were analyzed in a subset of 98 patients (47 CRE carriers and 51 non-CRE carriers) using whole metagenome sequences. The concomitant use of proton pump inhibitors (PPIs) and antibiotics was a significant risk factor for CRE colonization. The gut microbiome differed according to PPI administration, even within the CRE and non-CRE groups. Moreover, the transfer of mobile genetic elements (MGEs) harboring carbapenem resistance genes (CRGs) between bacteria was higher in the PPI-treated group than in the PPI-not-treated group among CRE carriers. The concomitant use of PPIs and antibiotics significantly alters the gut microbiome and increases the risk of CRE colonization by facilitating the transfer of CRGs among bacteria of the gut microbiome. Based on these findings, improved stewardship of PPIs as well as antibiotics can provide strategies to reduce the risk of CRE colonization, thereby potentially improving patient prognosis.
摘要：
耐碳青霉烯类肠杆菌(CRE)构成全球健康威胁;然而,对CRE在肠道微生物组中定植的危险因素和潜在机制的理解仍然有限。我们进行了一项涉及282名重症监护病房患者的配对病例对照研究，以分析影响CRE定植的协变量。随后，在98例患者(47例CRE携带者和51例非CRE携带者)的亚组中,使用完整宏基因组序列分析了它们对肠道微生物组的影响.同时使用质子泵抑制剂（PPI）和抗生素是CRE定植的重要风险因素。肠道微生物组根据PPI的施用而有所不同，甚至在CRE和非CRE组中。此外，在CRE携带者中,携带碳青霉烯耐药基因(CRGs)的可移动遗传元件(MGEs)在细菌之间的转移在PPI治疗组高于PPI未治疗组.PPI和抗生素的伴随使用通过促进CRG在肠道微生物组的细菌之间的转移来显著改变肠道微生物组并增加CRE定植的风险。基于这些发现,改善PPI和抗生素的管理可以提供降低CRE定植风险的策略，从而潜在地改善患者预后。
