Weber Daniela, Jenq Robert R, Peled Jonathan U, Taur Ying, Hiergeist Andreas, Koestler Josef, Dettmer Katja, Weber Markus, Wolff Daniel, Hahn Joachim, Pamer Eric G, Herr Wolfgang, Gessner André, Oefner Peter J, van den Brink Marcel R M, Holler Ernst
Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Biol Blood Marrow Transplant. 2017 May;23(5):845-852. doi: 10.1016/j.bbmt.2017.02.006. Epub 2017 Feb 14.
In allogeneic stem cell transplantation (ASCT), systemic broad-spectrum antibiotics are frequently used for treatment of infectious complications, but their effect on microbiota composition is still poorly understood. This retrospective analysis of 621 patients who underwent ASCT at the University Medical Center of Regensburg and Memorial Sloan Kettering Cancer Center in New York assessed the impact of timing of peritransplant antibiotic treatment on intestinal microbiota composition as well as transplant-related mortality (TRM) and overall survival. Early exposure to antibiotics was associated with lower urinary 3-indoxyl sulfate levels (P < .001) and a decrease in fecal abundance of commensal Clostridiales (P = .03) compared with late antibiotic treatment, which was particularly significant (P = .005) for Clostridium cluster XIVa in the Regensburg group. Earlier antibiotic treatment before ASCT was further associated with a higher TRM (34%, 79/236) compared with post-ASCT (21%, 62/297, P = .001) or no antibiotics (7%, 6/88, P < .001). Timing of antibiotic treatment was the dominant independent risk factor for TRM (HR, 2.0; P ≤ .001) in multivariate analysis besides increase age (HR, 2.15; P = .004), reduced Karnofsky performance status (HR, 1.47; P = .03), and female donor-male recipient sex combination (HR, 1.56; P = .02) A competing risk analysis revealed the independent effect of early initiation of antibiotics on graft-versus-host disease-related TRM (P = .004) in contrast to infection-related TRM and relapse (not significant). The poor outcome associated with early administration of antibiotic therapy that is active against commensal organisms, and specifically the possibly protective Clostridiales, calls for the use of Clostridiales-sparing antibiotics and rapid restoration of microbiota diversity after cessation of antibiotic treatment.
在异基因干细胞移植（ASCT）中，系统性广谱抗生素常用于治疗感染性并发症，但其对微生物群组成的影响仍知之甚少。这项对在雷根斯堡大学医学中心和纽约纪念斯隆凯特琳癌症中心接受ASCT的621例患者的回顾性分析，评估了移植前后抗生素治疗时机对肠道微生物群组成以及移植相关死亡率（TRM）和总生存率的影响。与晚期抗生素治疗相比，早期接触抗生素与较低的尿3-吲哚硫酸盐水平（P < 0.001）以及共生梭菌目粪便丰度降低（P = 0.03）相关，在雷根斯堡组中，这对梭菌属XIVa簇尤为显著（P = 0.005）。与ASCT后（21%，62/297，P = 0.001）或不使用抗生素（7%，6/88，P < 0.001）相比，ASCT前更早使用抗生素还与更高的TRM（34%，79/236）相关。在多变量分析中，除了年龄增加（HR，2.15；P = 0.004）、卡诺夫斯基功能状态降低（HR，1.47；P = 0.03）和女性供体-男性受体性别组合（HR，1.56；P = 0.02）外，抗生素治疗时机是TRM的主要独立危险因素（HR，2.0；P ≤ 0.001）。一项竞争风险分析显示，与感染相关的TRM和复发（不显著）相比，早期开始使用抗生素对移植物抗宿主病相关TRM有独立影响（P = .004）。与对共生生物（特别是可能具有保护作用的梭菌目）有活性的抗生素早期给药相关的不良结局，要求使用保留梭菌目的抗生素，并在抗生素治疗停止后迅速恢复微生物群多样性。
