Xu Dongyan, Mana Thriveen S C, Cadnum Jennifer L, Deshpande Abhishek, Afsari Faezeh, Sangwan Naseer, Donskey Curtis J
Case Western Reserve University School of Medicine, Cleveland, Ohio.
Research Service, Cleveland VA Medical Center, Cleveland, Ohio.
Pathog Immun. 2022 Jun 21;7(1):81-94. doi: 10.20411/pai.v7i1.512. eCollection 2022.
Clinical studies suggest that doxycycline poses a low risk for promotion of infection, but the microbiologic explanation for this finding is unclear.
Mice treated with oral doxycycline, oral azithromycin, subcutaneous ceftriaxone, doxycycline plus ceftriaxone, or azithromycin plus ceftriaxone were challenged with 10 colony-forming units of 2 different strains on day 2 of 5 of treatment. The concentration of was measured in stool 2 and 5 days after challenge. The impact of the treatments on the microbiota was assessed by sequencing.
Doxycycline and azithromycin treatment did not promote colonization by either strain in comparison to saline controls. Doxycycline treatment significantly reduced ceftriaxone-induced overgrowth of a strain with doxycycline minimum-inhibitory concentration (MIC) of 0.06 µg/mL (<0.01) but not a strain with doxycycline MIC of 48 µg/mL (>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.
These findings suggest that doxycycline may have a low propensity to promote colonization because it causes relatively limited alteration of the indigenous microbiota that provide colonization resistance and because it provides inhibitory activity against some strains.
临床研究表明，强力霉素引发感染的风险较低，但这一发现的微生物学解释尚不清楚。
在治疗的第2天和第5天，用口服强力霉素、口服阿奇霉素、皮下注射头孢曲松、强力霉素加头孢曲松或阿奇霉素加头孢曲松处理的小鼠，分别用2种不同菌株的10个菌落形成单位进行攻击。在攻击后2天和5天测量粪便中的浓度。通过测序评估治疗对微生物群的影响。
与生理盐水对照组相比，强力霉素和阿奇霉素治疗均未促进任何一种菌株的定植。强力霉素治疗显著降低了头孢曲松诱导的对强力霉素最低抑菌浓度（MIC）为0.06µg/mL的一种菌株的过度生长（<0.01），但未降低对强力霉素MIC为48µg/mL的菌株的过度生长（>0.05）；阿奇霉素治疗未降低头孢曲松诱导的任何一种菌株的过度生长。16S rRNA扩增子测序显示，与强力霉素治疗组和阿奇霉素治疗组小鼠相比，头孢曲松治疗组小鼠粪便中的细菌多样性显著降低。
这些发现表明，强力霉素促进定植的倾向可能较低，因为它对提供定植抗性的原生微生物群造成的改变相对有限，并且因为它对某些菌株具有抑制活性。
