中文摘要：背景：缩短抗生素治疗持续时间是抗生素管理的一项关键建议，但证据不足。本文调查了将抗生素疗程减半是否会减少革兰氏阴性菌血症患者肠道菌群的抗生素耐药基因（ARG）。
方法：研究对象包括病例组和对照组，前者为日内瓦大学医院（瑞士）住院的成年患者，他们参与了PIRATE随机试验，评估革兰氏阴性菌血症（病例）较短抗生素疗程（7天与14天）的非劣效性；后者为人口统计学和共病率相似但未接受抗生素治疗的住院患者。分别收集病例组患者抗生素使用后第7天、第14天、第30天和第90天以及对照组患者入院后第7天和第14天的粪便，并通过鸟枪法全宏基因组测序进行分析。主要结果是第30天的ARG丰度；次要结果为随时间推移，菌群的物种组成和聚集。
结果：45名病例和11名对照纳入评估；对29名接受7（+/-2）天或14（+/-3）天抗生素治疗的病例进行ARG分析。在第30天，接受治疗7天和14天的患者未检测到类似丰度的ARG（中位数计数/百万[mCPM]：96 vs 71；p=0.38）。第30天，两组之间的总ARG含量与第7天对照组无显著差异（362和370 mCPM vs 314 mCPM，p=0.24和0.19）。病例组患者在任何时间点的细菌多样性或聚集性均无显著差异，但与对照组相比，香农物种多样性在第14天显著降低（第7天组和第14天组的中位数分别为3.12和3.24，而对照组为3.61；p=0.04和0.012）。与其他患者相比，治疗14天的患者在治疗期间和治疗后粪便噬菌体含量降低。
结论：将抗生素使用时间缩短一半不会降低革兰氏阴性菌血症患者ARG丰度，也不会改善菌群物种多样性。
外文摘要：Background: Shortening antibiotic-treatment durations is a key recommendation of antibiotic-stewardship programmes, yet it is based on weak evidence. We investigated whether halving antibiotic courses would reduce antibiotic-resistance genes (ARG) in the intestinal microbiomes of patients treated for gram-negative bacteraemia.
   Methods: This nested prospective cohort study included adult patients hospitalized at Geneva University Hospitals (Switzerland) participating in the PIRATE randomized trial assessing non-inferiority of shorter antibiotic courses (7 versus 14 days) for gram-negative bacteraemia ('cases') and, simultaneously, hospitalized patients with similar demography and comorbidity yet no antibiotic therapy ('controls'). Stool was collected from case and control patients on days 7, 14, 30 and 90 after antibiotic initiation (day 1) and days 7 and 14 after admission, respectively, and analysed by whole-metagenome shotgun sequencing. The primary outcome was ARG abundance at day 30; secondary outcomes included microbiota-species composition and clustering over time.
   Findings: Forty-five patients and 11 controls were included and evaluable; ARG analyses were conducted on the 29 per-protocol patients receiving 7 (+/- 2) days or 14 (+/- 3) days of antibiotic therapy. At day 30, ARGs were not detected at similar abundance in patients receiving 7 and 14 days (median counts/million [mCPM]: 96 versus [vs] 71; p=.38). By day 30, total ARG content between both groups was not significantly different from that of controls at D7 (362 and 370 mCPM vs 314 mCPM, p=.24 and 0.19). There were no significant differences amongst antibiotic-treated patients at any timepoint in bacterial diversity or clustering, but Shannon species diversity was significantly reduced compared to controls through day 14 (median 3.12 and 3.24 in the 7-day and 14-day groups vs 3.61 [controls]; p=.04 and 0.012). Patients treated for 14 days had reduced faecal phage content during and after therapy compared to other patient groups.
   Interpretation: Reducing antibiotic durations by half did not result in decreased abundance of ARGs in patients treated for gram-negative bacteraemia, nor did it improve microbiota species diversity.
外文关键词：Resistome；Antibiotics；Faecal microbiota；Whole-metagenome shotgun sequencing；Treatment duration
作者：Leo, S；Lazarevic, V；von Dach, E；Kaiser, L；Prendki, V；Schrenzel, J；Huttner, BD；Huttner, A
作者单位：Univ Hosp；Univ Geneva；Geneva Univ Hosp；Fac Med；Hop Trois Chene
期刊名称：EBIOMEDICINE
期刊影响因子：5.736
出版年份：2021
出版刊次：
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