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头孢曲松和替莫西林对小鼠模型中产超广谱β-内酰胺酶大肠杆菌粪便丰度的影响。

Impact of ceftriaxone and temocillin on fecal abundance of extended-spectrum β-lactamase producing Escherichia coli in a mouse model.

机构信息

Microbiology Laboratory, Angers University Hospital, Angers, France.

Center for Research in Cancerology and Immunology Nantes-Angers, UMRS1232, Institut National de la Santé et de la Recherche Médicale, Université de Nantes, Université d'Angers, Angers, France.

出版信息

PLoS One. 2021 Mar 10;16(3):e0248177. doi: 10.1371/journal.pone.0248177. eCollection 2021.

Abstract

BACKGROUND

Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice.

METHODS

Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations.

RESULTS

Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar.

CONCLUSION

Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.

摘要

背景

产超广谱β-内酰胺酶(ESBL)肠杆菌科(ESBL-PE)在肠道中的定植较为广泛,并且会受到抗生素暴露的促进。粪便中 ESBL-PE 的丰度较高会促进细菌在环境中的传播,并与感染风险增加相关。头孢曲松和替莫西林是两种常用的抗生素,对肠道菌群的作用不同。它们对产 ESBL 肠杆菌在粪便中丰度的影响尚未得到研究。本研究的目的是比较头孢曲松和替莫西林对定植于小鼠肠道的产 ESBL 大肠埃希菌丰度的改变作用。

方法

小鼠接受广谱抗生素治疗以破坏其正常肠道菌群。然后,通过口服给予 CTX-M 型产 ESBL 大肠埃希菌临床分离株,导致持久定植。30 天后,小鼠通过饮用水接受替莫西林或头孢曲松治疗,浓度模拟人类肠道暴露。在抗生素暴露结束前、结束后 2 天和 10 天,在选择性培养基上对粪便中的第三代头孢菌素耐药(3GCR)大肠埃希菌进行计数。使用两种 MIC 值不同的替莫西林的大肠埃希菌分离株进行了实验。

结果

暴露于头孢曲松会导致粪便中 3GCR 大肠埃希菌丰度增加。相比之下,替莫西林对 3GCR 大肠埃希菌的数量没有影响或短暂减少。两种菌株的结果相似。

结论

与头孢曲松不同,替莫西林不会促进定植于小鼠肠道的产 ESBL 大肠埃希菌的扩张。因此,当怀疑或证实存在先前定植患者的 ESBL-PE 扩张时,替莫西林可能是一种治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c7/7946171/2121c46702fb/pone.0248177.g001.jpg

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