Healthcare-Associated Infections Group, Leeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds LS1 9JT, UK.
J Antimicrob Chemother. 2021 Jan 1;76(1):171-178. doi: 10.1093/jac/dkaa386.
The approval of new antibiotics is essential to combat infections caused by antimicrobial-resistant pathogens; however, such agents should be tested to determine their effect on the resident microbiota and propensity to select for opportunistic pathogens, such as Clostridioides difficile. Eravacycline is a new antibiotic for the treatment of complicated intra-abdominal infections. Here, we determined the effects of eravacycline compared with moxifloxacin on the microbiota and if these were conducive to induction of C. difficile infection (CDI).
We seeded in vitro chemostat models, which simulate the physiological conditions of the human colon, with a human faecal slurry and instilled gut-reflective concentrations of either eravacycline or moxifloxacin.
Eravacycline instillation was associated with decreased Bifidobacterium, Lactobacillus and Clostridium species, which recovered 1 week after exposure. However, Bacteroides spp. levels decreased to below the limit of detection and did not recover prior to the end of the experiment. Post-eravacycline, a bloom of aerobic bacterial species occurred, including Enterobacteriaceae, compared with pre-antibiotic, which remained high for the duration of the experiment. These changes in microbiota were not associated with induction of CDI, as we observed a lack of C. difficile spore germination and thus no toxin was detected. Moxifloxacin exposure sufficiently disrupted the microbiota to induce simulated CDI, where C. difficile spore germination, outgrowth and toxin production were seen.
These model data suggest that, despite the initial impact of eravacycline on the intestinal microbiota, similar to clinical trial data, this novel tetracycline has a low propensity to induce CDI.
新抗生素的批准对于对抗由抗微生物药物耐药性病原体引起的感染至关重要；然而，应该对这些药物进行测试，以确定它们对常驻微生物群的影响，以及它们选择机会性病原体（如艰难梭菌）的倾向。依拉环素是一种用于治疗复杂腹腔内感染的新型抗生素。在这里，我们确定了依拉环素与莫西沙星相比对微生物群的影响，以及这些影响是否有利于诱导艰难梭菌感染（CDI）。
我们使用人体粪便接种了体外恒化器模型，这些模型模拟了人类结肠的生理条件，并注入了肠道反射浓度的依拉环素或莫西沙星。
依拉环素的注入与双歧杆菌、乳杆菌和梭菌的减少有关，这些菌在暴露后 1 周内恢复。然而，拟杆菌的水平下降到检测限以下，并且在实验结束前没有恢复。在依拉环素之后，出现了需氧细菌物种的大量繁殖，包括肠杆菌科，与抗生素前相比，这些细菌在实验过程中一直保持较高水平。这些微生物群的变化与 CDI 的诱导无关，因为我们观察到没有艰难梭菌孢子发芽，因此没有检测到毒素。莫西沙星暴露足以破坏微生物群，从而诱导模拟 CDI，其中可以观察到艰难梭菌孢子发芽、生长和毒素产生。
这些模型数据表明，尽管依拉环素对肠道微生物群有最初的影响，但与临床试验数据相似，这种新型四环素诱导 CDI 的倾向较低。
