Chilton C H, Crowther G S, Miossec C, de Gunzburg J, Andremont A, Wilcox M H
Healthcare Associated Infections Research Group, Leeds Institute for Medical Research, University of Leeds, Old Medical School, Leeds General Infirmary, Leeds LS1 3EX, UK.
Division of Pharmacy and Optometry, University of Manchester, Manchester M13 9PT, UK.
J Antimicrob Chemother. 2020 Jun 1;75(6):1458-1465. doi: 10.1093/jac/dkaa062.
Clostridioides difficile infection (CDI) remains a high burden worldwide. DAV131A, a novel adsorbent, reduces residual gut antimicrobial levels, reducing CDI risk in animal models.
We used a validated human gut model to investigate the efficacy of DAV131A in preventing moxifloxacin-induced CDI.
C. difficile (CD) spores were inoculated into two models populated with pooled human faeces. Moxifloxacin was instilled (43 mg/L, once daily, 7 days) alongside DAV131A (5 g in 18 mL PBS, three times daily, 14 days, Model A), or PBS (18 mL, three times daily, 14 days, Model B). Selected gut microbiota populations, CD total counts, spore counts, cytotoxin titre and antimicrobial concentrations (HPLC) were monitored daily. We monitored for reduced susceptibility of CD to moxifloxacin. Growth of CD in faecal filtrate and medium in the presence/absence of DAV131A, or in medium pre-treated with DAV131A, was also investigated.
DAV131A instillation reduced active moxifloxacin levels to below the limit of detection (50 ng/mL), and prevented microbiota disruption, excepting Bacteroides fragilis group populations, which declined by ∼3 log10 cfu/mL. DAV131A delayed onset of simulated CDI by ∼2 weeks, but did not prevent CD germination and toxin production. DAV131A prevented emergence of reduced susceptibility of CD to moxifloxacin. In batch culture, DAV131A had minor effects on CD vegetative growth, but significantly reduced toxin/spores (P < 0.005).
DAV131A reduced moxifloxacin-induced microbiota disruption and emergence of antibiotic-resistant CD. Delayed onset of CD germination and toxin production indicates further investigations are warranted to understand the clinical benefits of DAV131A in CDI prevention.
艰难梭菌感染（CDI）在全球范围内仍然是一个沉重的负担。新型吸附剂DAV131A可降低肠道内残留的抗菌药物水平，降低动物模型中CDI的风险。
我们使用经过验证的人体肠道模型来研究DAV131A预防莫西沙星诱导的CDI的疗效。
将艰难梭菌（CD）孢子接种到两个接种了混合人粪便的模型中。莫西沙星（43 mg/L，每日一次，共7天）与DAV131A（5 g溶于18 mL PBS中，每日三次，共14天，模型A）或PBS（18 mL，每日三次，共14天，模型B）一起滴注。每天监测选定的肠道微生物群、CD总数、孢子数、细胞毒素滴度和抗菌药物浓度（高效液相色谱法）。我们监测CD对莫西沙星敏感性降低的情况。还研究了在有无DAV131A的情况下，或在经DAV131A预处理的培养基中，CD在粪便滤液和培养基中的生长情况。
滴注DAV131A可将活性莫西沙星水平降低至检测限（50 ng/mL）以下，并防止微生物群受到破坏，但脆弱拟杆菌群数量除外，其数量下降了约3 log10 cfu/mL。DAV131A将模拟CDI的发病时间推迟了约2周，但并未阻止CD的萌发和毒素产生。DAV131A可防止CD对莫西沙星敏感性降低的情况出现。在分批培养中，DAV131A对CD的营养生长影响较小，但显著降低了毒素/孢子水平（P < 0.005）。
DAV131A可减少莫西沙星诱导的微生物群破坏和耐抗生素CD的出现。CD萌发和毒素产生的延迟表明有必要进一步研究以了解DAV131A在预防CDI方面的临床益处。
