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异基因造血干细胞移植患者省略环丙沙星预防用药及其对临床结局和微生物组结构的影响

Omitting Ciprofloxacin Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation and Its Impact on Clinical Outcomes and Microbiome Structure.

作者信息

Daoud-Asfour Haneen, Henig Israel, Ghersin Itai, Rakedzon Stav, Stern Anat, Pitashny Milena, Zuckerman Tsila, Bar-Yoseph Haggai

机构信息

Department of Nephrology, Rambam Health Care Campus, Haifa, Israel.

Department of Hematology, Rambam Health Care Campus, Haifa, Israel.

出版信息

Transplant Cell Ther. 2022 Mar;28(3):168.e1-168.e8. doi: 10.1016/j.jtct.2021.12.012. Epub 2021 Dec 23.

Abstract

Fluoroquinolone prophylaxis during allogeneic hematopoietic stem cell transplantation (allo-HSCT) reduces bloodstream infections. However, this practice affects the gut microbiome and potentially increases dysbiosis, which is closely related to transplantation outcomes, and lower gastrointestinal (GI) tract acute graft-versus-host disease (GVHD). This study assessed the impact of omitting ciprofloxacin prophylaxis on GI GVHD, clinical outcomes, and microbiome composition in patients undergoing allo-HSCT. In this single-center, retrospective study comprising recipients of allo-HSCT performed between 2018 and 2020, routine ciprofloxacin prophylaxis (the exposure variable) was stopped in December 2018. The primary outcome was acute lower GI GVHD within 100 days post-transplantation; secondary outcomes were 1-year overall survival, nonrelapse mortality, relapse, and overall acute GVHD. Outcomes were compared using univariate and multivariate analyses and Kaplan-Meier/competing-risk analyses. Sequential stool samples were collected prospectively from a subpopulation of recipients, and the microbiome composition was analyzed. Seventy-five of the 129 patients (58.1%) received prophylactic ciprofloxacin treatment. Baseline characteristics did not differ between the 2 study groups: patients with ciprofloxacin prophylaxis and those without ciprofloxacin prophylaxis. The rate of lower GI GVHD also did not differ between the 2 groups (24% versus 18.5%; P = .597). None of the secondary outcomes was significantly different between the 2 groups in univariate, multivariate, and time-to-event analyses. In addition, microbiome analysis in a subpopulation of 22 patients did not reveal any significant between-group difference in alpha or beta diversity. Omitting prophylactic ciprofloxacin during allo-HSCT did not affect microbiome composition, lower GI-GVHD rate, or other significant clinical outcomes. The use of prophylactic antibiotics in this setting should be evaluated further.

摘要

异基因造血干细胞移植(allo-HSCT)期间使用氟喹诺酮类药物进行预防可减少血流感染。然而,这种做法会影响肠道微生物群,并可能增加与移植结果密切相关的生态失调以及下消化道急性移植物抗宿主病(GVHD)。本研究评估了在接受allo-HSCT的患者中省略环丙沙星预防对胃肠道GVHD、临床结局和微生物群组成的影响。在这项单中心回顾性研究中,纳入了2018年至2020年间接受allo-HSCT的患者,2018年12月停止了常规环丙沙星预防(暴露变量)。主要结局是移植后100天内的急性下消化道GVHD;次要结局是1年总生存率、非复发死亡率、复发率和总体急性GVHD。使用单因素和多因素分析以及Kaplan-Meier/竞争风险分析对结局进行比较。前瞻性地从一部分受者中收集连续的粪便样本,并分析微生物群组成。129例患者中有75例(58.1%)接受了预防性环丙沙星治疗。两个研究组之间的基线特征无差异:接受环丙沙星预防的患者和未接受环丙沙星预防的患者。两组之间下消化道GVHD的发生率也无差异(24%对18.5%;P = 0.597)。在单因素、多因素和事件发生时间分析中,两组之间的次要结局均无显著差异。此外,对22例患者亚组的微生物群分析未发现两组之间在α或β多样性方面有任何显著差异。在allo-HSCT期间省略预防性环丙沙星不会影响微生物群组成、下消化道GVHD发生率或其他显著的临床结局。在此情况下预防性抗生素的使用应进一步评估。

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