Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.
Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.
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DOI：
10.1016/j.anaerobe.2021.102387
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发表时间：
2021-08
期刊：
影响因子：
2.3
通讯作者：
Garey KW
中科院分区：
文献类型：
--
作者：
Gonzales-Luna AJ;Spinler JK;Oezguen N;Khan MAW;Danhof HA;Endres BT;Alam MJ;Begum K;Lancaster C;Costa GP;Savidge TC;Hurdle JG;Britton R;Garey KW
粪便微生物群移植（FMT）旨在通过重建健康的微生物组和恢复定植抵抗力来治愈艰难梭菌感染（CDI）。虽然一次输注后通常有效，但微生物组持续破坏的患者可能需要多次 FMT。在这项 N-of-1 研究中，我们使用系统生物学方法来评估一名接受慢性抑制性抗生素且两年内 4 次 FMT 失败的患者的 CDI。 2016-18 年间，患者接受了 5 次 FMT，期间获得了 7 份粪便样本。对粪便样本进行艰难梭菌培养，并使用鸟枪法宏基因组学进行微生物表征和功能基因分析。通过核糖分型、全基因组测序、代谢途径分析和最低抑菌浓度 (MIC) 测定来表征艰难梭菌分离株。每个样品生长十个菌株，索引和前四个循环培养物是单菌株核糖型F078-126，第五个是核糖型F002和F054的混合培养物，最终培养物是核糖型F002。与之前的 F078-126 菌株相比，最终分离的 F078-126 菌株的 RNA 聚合酶 (RNAP) β 亚基 RpoB 中发现了一个单核苷酸多态性 (SNP) 变异。该 SNV 与代谢变化相关，但未观察到非达霉素 MIC 的表型差异。在万古霉素治疗期间和 FMT 失败后，随着时间的推移观察到微生物组的差异。这项研究强调了抗菌药物管理对于接受 FMT 的患者的重要性。持续的抗生素对移植的微生物组发挥破坏性作用，并对少数可用于治疗 CDI 的抗生素施加选择压力，产生耐药性。
Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years. Seven stool samples were obtained between 2016-18 while the patient underwent five FMTs. Stool samples were cultured for C. difficile and underwent microbial characterization and functional gene analysis using shotgun metagenomics. C. difficile isolates were characterized through ribotyping, whole genome sequencing, metabolic pathway analysis, and minimum inhibitory concentration (MIC) determinations. Growing ten strains from each sample, the index and first four recurrent cultures were single strain ribotype F078-126, the fifth was a mixed culture of ribotypes F002 and F054, and the final culture was ribotype F002. One single nucleotide polymorphism (SNP) variant was identified in the RNA polymerase (RNAP) β-subunit RpoB in the final isolated F078-126 strain when compared to previous F078-126 isolates. This SNV was associated with metabolic shifts but phenotypic differences in fidaxomicin MIC were not observed. Microbiome differences were observed over time during vancomycin therapy and after failed FMTs. This study highlights the importance of antimicrobial stewardship in patients receiving FMT. Continued antibiotics play a destructive role on a transplanted microbiome and applies selection pressure for resistance to the few antibiotics available to treat CDI.
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美国梭菌艰难梭菌感染和结果负担的趋势。
DOI：
10.1056/nejmoa1910215
发表时间：
2020-04-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guh AY;Mu Y;Winston LG;Johnston H;Olson D;Farley MM;Wilson LE;Holzbauer SM;Phipps EC;Dumyati GK;Beldavs ZG;Kainer MA;Karlsson M;Gerding DN;McDonald LC;Emerging Infections Program Clostridioides difficile Infection Working Group
通讯作者：
Emerging Infections Program Clostridioides difficile Infection Working Group
DOI：
10.1093/jac/dkv498
发表时间：
2016-05
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Bassères E;Endres BT;Khaleduzzaman M;Miraftabi F;Alam MJ;Vickers RJ;Garey KW
通讯作者：
Garey KW
影响因子：
15.5
作者：
Fadrosh DW;Ma B;Gajer P;Sengamalay N;Ott S;Brotman RM;Ravel J
通讯作者：
Ravel J
DOI：
10.1093/cid/cis499
发表时间：
2012-08
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Crook DW;Walker AS;Kean Y;Weiss K;Cornely OA;Miller MA;Esposito R;Louie TJ;Stoesser NE;Young BC;Angus BJ;Gorbach SL;Peto TE;Study 003/004 Teams
通讯作者：
Study 003/004 Teams
影响因子：
11.8
作者：
Beyda, Nicholas D.;John, Julie;Garey, Kevin W.
通讯作者：
Garey, Kevin W.