Department of Hematology and Oncology, Internal Medicine III, University Medical Center, Regensburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Medical Center, Regensburg, Germany.
Clin Infect Dis. 2019 Apr 8;68(8):1303-1310. doi: 10.1093/cid/ciy711.
Maintaining gastrointestinal (GI) microbiome diversity plays a key role during allogeneic stem cell transplantation (ASCT), and loss of diversity correlates with acute GI graft versus host disease (GvHD) and poor outcomes.
In this retrospective analysis of 161 ASCT patients, we used serial analyses of urinary 3-indoxyl sulfate (3-IS) levels and GI microbiome parameters within the first 10 days after ASCT to identify potential commensal microbiota-sparing antibiotics. Based on antibiotic activity, we formed 3 subgroups (Rifaximin without systemic antibiotics, Rifaximin with systemic antibiotics, and Ciprofloxacin/Metronidazole with/without systemic antibiotics).
Mono-antibiosis with Rifaximin revealed higher 3-IS levels (P < .001), higher Clostridium cluster XIVa (CCXIVa) abundance (P = .004), and higher Shannon indices (P = .01) compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics. Rifaximin followed by systemic antibiotics maintained microbiome diversity compared to Ciprofloxacin/Metronidazole with/without systemic antibiotics, as these patients showed still higher 3-IS levels (P = .04), higher CCXIVa copy numbers (P = .01), and higher Shannon indexes (P = .01). Even for this larger cohort of patients, the outcome was superior with regard to GI GvHD (P = .05) and lower transplant-related mortality (P < .001) for patients receiving Rifaximin plus systemic antibiotics compared to other types of systemic antibiotic treatment. Antibiosis with Ciprofloxacin/Metronidazole (n = 12, P = .01), Piperacillin/Tazobactam (n = 52, P = .01), Meropenem/Vancomycin (n = 16, P = .003), Ceftazidime (n = 10, P = .03), or multiple systemic antibiotics (n = 53, P = .001) showed significantly lower 3-IS levels compared to mono-antibiosis with Rifaximin (n = 14) or intravenous Vancomycin (n = 4, not statistically significant).
Different types of antibiotic treatments show different impacts on markers of microbiome diversity. The identification of antibiotics sparing commensal bacteria remains an ongoing challenge. However, Rifaximin allowed a higher intestinal microbiome diversity, even in the presence of systemic broad-spectrum antibiotics.
在异基因造血干细胞移植（ASCT）期间，维持胃肠道（GI）微生物组多样性起着关键作用，多样性的丧失与急性 GI 移植物抗宿主病（GvHD）和不良预后相关。
在这项对 161 例 ASCT 患者的回顾性分析中，我们使用移植后第 10 天内的尿液 3-吲哚硫酸（3-IS）水平和 GI 微生物组参数的连续分析，以确定潜在的共生菌群保护抗生素。根据抗生素的活性，我们形成了 3 个亚组（无全身抗生素的利福昔明、有全身抗生素的利福昔明和有/无全身抗生素的环丙沙星/甲硝唑）。
与环丙沙星/甲硝唑联合全身抗生素相比，单抗生素利福昔明显示出更高的 3-IS 水平（P <.001）、更高的梭状芽胞杆菌簇 XIVa（CCXIVa）丰度（P =.004）和更高的香农指数（P =.01）。与环丙沙星/甲硝唑联合全身抗生素相比，利福昔明联合全身抗生素维持了微生物组的多样性，因为这些患者的 3-IS 水平仍更高（P =.04）、CCXIVa 拷贝数更高（P =.01）和香农指数更高（P =.01）。即使对于这一大队列患者，与其他类型的全身抗生素治疗相比，接受利福昔明联合全身抗生素治疗的患者胃肠道 GvHD （P =.05）和移植相关死亡率（P <.001）均更高。与单抗生素利福昔明（n = 14）或静脉万古霉素（n = 4，无统计学意义）相比，环丙沙星/甲硝唑（n = 12，P =.01）、哌拉西林/他唑巴坦（n = 52，P =.01）、美罗培南/万古霉素（n = 16，P =.003）、头孢他啶（n = 10，P =.03）或多种全身抗生素（n = 53，P =.001）的抗生素治疗显著降低了 3-IS 水平。
不同类型的抗生素治疗对微生物组多样性的标志物有不同的影响。识别保护共生细菌的抗生素仍然是一个持续的挑战。然而，利福昔明允许更高的肠道微生物组多样性，即使存在全身广谱抗生素。
