Crowther Grace S, Chilton Caroline H, Todhunter Sharie L, Nicholson Scott, Freeman Jane, Wilcox Mark H
Leeds Institute of Biomedical and Clinical Sciences, Faculty of Medicine and Health, University of Leeds, Leeds, UK.
Department of Microbiology, Leeds Teaching Hospitals NHS Trust, The General Infirmary, Leeds, UK.
J Antimicrob Chemother. 2015 Aug;70(8):2316-21. doi: 10.1093/jac/dkv108. Epub 2015 Apr 29.
Clostridium difficile infection (CDI) is still a major challenge to healthcare facilities. The detection of multiple C. difficile strains has been reported in some patient samples during initial and recurrent CDI episodes. However, the behaviour of individual strains and their contribution to symptomatic disease is unclear.
An in vitro human gut model was used to investigate the germination and proliferation of two distinct C. difficile strains during initial and recurrent simulated CDI, as well as their response to vancomycin treatment. The gut model was inoculated with a pooled human faecal emulsion and indigenous gut microbiota, C. difficile populations (vegetative and spore forms), cytotoxin levels and antimicrobial activity were monitored throughout the experiment.
Both C. difficile strains germinated and proliferated in response to ceftriaxone instillation, with cytotoxin detected during the peak vegetative growth. Vancomycin instillation resulted in a rapid decline in the vegetative forms of both strains, with only spores remaining 2 days after the start of dosing. A recrudescence of both strains occurred following the cessation of vancomycin installation, although this was observed more quickly, and to a greater extent, in one strain than the other.
Within a human gut model, multiple C. difficile strains are able to germinate and proliferate concurrently in response to antibiotic challenge (the onset of simulated CDI). Similarly, more than one strain can proliferate during simulated recurrent CDI, although with differences in germination and growth rate and timing. It appears probable that multiple strains can contribute to CDI within an individual patient, with possible implications for management and bacterial transmission.
艰难梭菌感染（CDI）仍是医疗机构面临的一项重大挑战。在一些患者样本的初次和复发性CDI发作期间，已报告检测到多种艰难梭菌菌株。然而，各个菌株的行为及其对症状性疾病的作用尚不清楚。
使用体外人体肠道模型研究两种不同的艰难梭菌菌株在初次和复发性模拟CDI期间的萌发和增殖情况，以及它们对万古霉素治疗的反应。用混合的人类粪便乳剂和肠道原生微生物群接种肠道模型，在整个实验过程中监测艰难梭菌种群（营养体和孢子形式）、细胞毒素水平和抗菌活性。
两种艰难梭菌菌株均对头孢曲松滴注产生反应而萌发和增殖，在营养体生长高峰期检测到细胞毒素。万古霉素滴注导致两种菌株的营养体形式迅速减少，给药开始2天后仅残留孢子。停止万古霉素滴注后，两种菌株均复发，不过其中一种菌株比另一种菌株复发得更快且程度更大。
在人体肠道模型中，多种艰难梭菌菌株能够在抗生素挑战（模拟CDI发作）后同时萌发和增殖。同样，在模拟复发性CDI期间，不止一种菌株能够增殖，尽管在萌发、生长速率和时间方面存在差异。看来多种菌株可能在个体患者的CDI中起作用，这可能对治疗管理和细菌传播产生影响。
