背景：缩短抗生素治疗持续时间是抗生素管理计划的主要建议，然而，它是基于薄弱的证据。我们调查了将抗生素疗程减半是否会减少接受革兰氏阴性菌血症治疗的患者的肠道微生物组中的抗生素抗性基因（ARG）。
方法：这项巢式前瞻性队列研究包括在日内瓦大学医院（瑞士）住院的成年患者，他们参加了PIRATE随机试验，评估了较短的抗生素疗程（7天与14天）对革兰氏阴性菌血症（\'病例\'）的非劣效性，同时,人口统计学和合并症相似但没有抗生素治疗的住院患者(“对照”)。在抗生素开始后第7、14、30和90天（第1天）以及入院后第7和14天从病例和对照组患者收集粪便，分别,并通过全基因组鸟枪测序进行分析。主要结果是第30天的ARG丰度；次要结果包括微生物群-物种组成和随时间的聚集。
结果：纳入45名患者和11名对照，可评价；对29名接受7(±2)天或14(±3)天抗生素治疗的符合方案患者进行ARG分析。在第30天，在接受7天和14天的患者中未检测到类似丰度的ARG（中位数计数/百万[mCPM]：96对[vs]71；p=0.38）。到第30天，两组之间的总ARG含量与D7时的对照组相比没有显着差异（362和370mCPMvs314mCPM，p=.24和0.19）。在任何时间点，抗生素治疗的患者在细菌多样性或聚集性方面都没有显着差异。但是直到第14天，与对照组相比，香农物种多样性显着降低（7天和14天组的中位数为3.12和3.24，而对照组为3.61；p=.04和0.012）。与其他患者组相比，治疗14天的患者在治疗期间和之后的粪便噬菌体含量降低。
结论：在接受革兰阴性菌血症治疗的患者中，将抗生素使用时间减少一半并没有导致ARGs丰度降低，它也没有改善微生物群物种多样性。
背景：该研究由日内瓦大学的路易-珍妮特基金会资助（批准号：S04_12）和瑞士国家科学基金会（NRPSmarterHealthcare，批准号407,440_167359)。
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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: The
study was funded by the University of Geneva\'s Louis-Jeantet Foundation (grant no. S04_12) and the Swiss National Science Foundation (NRP Smarter Healthcare, grant no. 407,440_167359).
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