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Differential effects of antibiotic treatment with piperacillin/tazobactam or ceftriaxone on the murine gut microbiota.
bioRxiv - Microbiology Pub Date : 2020-05-29 , DOI: 10.1101/2020.05.28.122473
Carola Venturini , Bethany Bowring , Alicia Fajardo-Lubian , Carol Devine , Jonathan Iredell

Effective antimicrobial stewardship requires a better understanding of the impact of different antibiotics on the gut microflora. Studies in humans are confounded by large inter-individual variability and difficulty in identifying control cohorts. However, controlled murine models can provide valuable information. We examined the impact of a penicillin-like antibiotic (piperacillin/tazobactam, TZP) or a third-generation cephalosporin (ceftriaxone, CRO) on the murine gut microbiota. We analyzed gut microbiome composition by 16S-rRNA amplicon sequencing and effects on the Enterobacteriaceae by qPCR and standard microbiology. Colonization resistance to multidrug resistant Escherichia coli ST131 and Klebsiella pneumoniae ST258 was also tested. Changes in microbiome composition and a significant (p<0.001) decrease in diversity occurred in all treated mice, but were more marked and longer lasting after CRO exposure with a persistent rise in Proteobacteria levels. Increases in the Enterobacteriaceae occurred in all antibiotic treated mice, but were transient and associated with direct antibiotic pressure. Co-habitation of treated and untreated mice attenuated the detrimental effect of antibiotics on treated animals, but also caused disturbance in untreated co-habitants. At the height of dysbiosis after antibiotic termination, the murine gut was highly susceptible to colonization with both multidrug resistant pathogens. The administration of a third-generation cephalosporin caused a significantly prolonged dysbiosis in the murine gut microflora, when compared to a penicillin/β-lactam inhibitor combination with comparable activity against medically important virulent bacteria. At the height of dysbiosis, both antibiotic treatments equally led to microbial imbalance associated with loss of resistance to gut colonization by antibiotic-resistant pathogens.

中文翻译:

哌拉西林/他唑巴坦或头孢曲松抗生素治疗对小鼠肠道菌群的不同作用。

有效的抗菌管理需要​​更好地了解不同抗生素对肠道菌群的影响。人类之间的研究因个体之间的巨大差异和识别对照人群的难度而感到困惑。但是,受控的鼠模型可以提供有价值的信息。我们检查了类似青霉素的抗生素(哌拉西林/他唑巴坦,TZP)或第三代头孢菌素(头孢曲松,CRO)对鼠肠道菌群的影响。我们通过16S-rRNA扩增子测序分析了肠道微生物组组成,并通过qPCR和标准微生物学对肠杆菌科进行了分析。对耐多药性大肠杆菌ST131肺炎克雷伯菌的定植抗性ST258也经过测试。在所有接受治疗的小鼠中,微生物组组成的变化和多样性的显着降低(p <0.001)均发生,但在CRO暴露后,随着变形杆菌水平的持续升高,其变化更为明显且持续时间更长。肠杆菌科细菌的增加发生在所有用抗生素治疗的小鼠中,但都是短暂的,并与直接的抗生素压力有关。处理和未处理的小鼠的同居会减弱抗生素对处理过的动物的有害作用,但也会引起未处理的同居者的干扰。在抗生素终止后的共生异常高峰时,鼠肠道对两种耐多药病原体都非常敏感。第三代头孢菌素的使用会导致鼠肠道菌群的病态持续时间明显延长,与青霉素/β-内酰胺抑制剂组合相比,具有对医学上重要的强力细菌相当的活性。在营养不良的高峰期,两种抗生素治疗均会导致微生物失衡,进而导致对抗生素抵抗性病原体对肠道定殖的抵抗力下降。
更新日期:2020-05-29
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