Why Does Doxycycline Pose a Relatively Low Risk for Promotion of Clostridioides difficile Infection?

Q1 Medicine Pathogens and Immunity Pub Date : 2022-06-21 eCollection Date: 2022-01-01 DOI:10.20411/pai.v7i1.512
Dongyan Xu, Thriveen S C Mana, Jennifer L Cadnum, Abhishek Deshpande, Faezeh Afsari, Naseer Sangwan, Curtis J Donskey
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引用次数: 4

Abstract

Background: Clinical studies suggest that doxycycline poses a low risk for promotion of Clostridioides difficile infection, but the microbiologic explanation for this finding is unclear.

Methods: Mice treated with oral doxycycline, oral azithromycin, subcutaneous ceftriaxone, doxycycline plus ceftriaxone, or azithromycin plus ceftriaxone were challenged with 104 colony-forming units of 2 different C. difficile strains on day 2 of 5 of treatment. The concentration of C. difficile was measured in stool 2 and 5 days after challenge. The impact of the treatments on the microbiota was assessed by sequencing.

Results: Doxycycline and azithromycin treatment did not promote colonization by either C. difficile strain in comparison to saline controls. Doxycycline treatment significantly reduced ceftriaxone-induced overgrowth of a C. difficile strain with doxycycline minimum-inhibitory concentration (MIC) of 0.06 µg/mL (P<0.01) but not a strain with doxycycline MIC of 48 µg/mL (P>0.05); azithromycin treatment did not reduce ceftriaxone-induced overgrowth of either strain. 16S rRNA amplicon sequencing revealed significantly lower bacterial diversity in the stool of ceftriaxone-treated mice, in comparison to doxycycline-treated and azithromycin-treated mice.

Conclusions: These findings suggest that doxycycline may have a low propensity to promote C. difficile colonization because it causes relatively limited alteration of the indigenous microbiota that provide colonization resistance and because it provides inhibitory activity against some C. difficile strains.

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为什么强力霉素促进艰难梭菌感染的风险相对较低?
背景:临床研究表明,强力霉素促进艰难梭菌感染的风险较低,但这一发现的微生物学解释尚不清楚。方法:口服多西环素、口服阿奇霉素、皮下注射头孢曲松、多西环素加头孢曲松或阿奇霉素加头孢曲松治疗小鼠,在治疗第5天的第2天感染2种不同的艰难梭菌104个菌落形成单位。攻毒后第2天和第5天测定粪便中艰难梭菌的浓度。通过测序评估处理对微生物群的影响。结果:与生理盐水对照组相比,强力霉素和阿奇霉素治疗没有促进艰难梭菌的定植。强力霉素处理显著降低头孢曲松诱导的艰难梭菌过度生长,强力霉素最低抑制浓度(MIC)为0.06µg/mL (PP>0.05);阿奇霉素治疗并没有减少头孢曲松诱导的两种菌株的过度生长。16S rRNA扩增子测序显示,与多西环素和阿奇霉素处理的小鼠相比,头孢曲松处理的小鼠粪便中细菌多样性显著降低。结论:这些发现表明强力霉素可能具有较低的促进艰难梭菌定植的倾向,因为它对提供定植抗性的本地微生物群的改变相对有限,并且因为它对某些艰难梭菌菌株具有抑制活性。
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来源期刊
Pathogens and Immunity
Pathogens and Immunity Medicine-Infectious Diseases
CiteScore
10.60
自引率
0.00%
发文量
16
审稿时长
10 weeks
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