Olivares Carlos, Ruppé Etienne, Ferreira Stéphanie, Corbel Tanguy, Andremont Antoine, de Gunzburg Jean, Guedj Jeremie, Burdet Charles
Université Paris Cité, IAME, INSERM, Paris, France.
APHP, Laboratoire de Bactériologie, Hôpital Bichat, Paris, France.
Gut Microbes. 2025 Dec;17(1):2442523. doi: 10.1080/19490976.2024.2442523. Epub 2024 Dec 22.
Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.
宏基因组测序加深了我们对肠道微生物群在人类健康中作用的认识，并且有几项采用不同方法的研究探讨了其在抗生素治疗期间的动态变化。我们比较了四种广泛使用的抗生素对肠道细菌多样性的影响。我们使用了健康志愿者在治疗期间及治疗后采集的血浆和粪便样本，这些志愿者被分配接受为期5天的治疗，治疗药物分别为头孢曲松（静脉注射，每24小时1克）、头孢他啶/阿维巴坦（静脉注射，每8小时2克/500毫克）、哌拉西林/他唑巴坦（静脉注射，每8小时1克/500毫克）或莫西沙星（口服，每24小时400毫克）。测量了血浆和粪便中的抗生素浓度，并通过16S rRNA基因谱的香农指数评估细菌多样性。使用非线性混合效应模型对抗生素粪便暴露演变与细菌多样性之间的关系进行建模。我们通过模拟，使用各种重建的药效学指标，比较了抗生素对肠道微生物群多样性的影响。哌拉西林/他唑巴坦在扰动强度方面影响最大（多样性最大[四分位间距]损失为27.3%[1.9；40.0]），而莫西沙星的扰动持续时间最长，最后一次给药后恢复到基线值95%的时间为13.2天[8.3；19.1]。总体而言，莫西沙星的总体影响最大，其次是哌拉西林/他唑巴坦、头孢他啶/阿维巴坦和头孢曲松。从第0天到第42天，它们多样性指数变化的曲线下面积分别为-13.2香农单位·天[-20.4；-7.9]、-10.9香农单位·天[-20.4；-0.6]和-10.1香农单位·天[-18.3；-4.6]。我们得出结论，抗生素会在不同程度上改变肠道多样性，无论是在抗生素家族内部还是之间。需要开展此类研究以助力抗生素管理，从而使用对肠道微生物群影响最小的抗生素。
