Recurrence of dual-strain Clostridium difficile infection in an in vitro human gut model
Recurrence of dual-strain Clostridium difficile infection in an in vitro human gut model
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DOI：
10.1093/jac/dkv108
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发表时间：
2015-08-01
影响因子：
5.2
通讯作者：
Wilcox, Mark H.
中科院分区：
文献类型：
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作者：
Crowther, Grace S.;Chilton, Caroline H.;Wilcox, Mark H.
背景：艰难梭菌感染（CDI）仍然是医疗机构面临的主要挑战。检测多种C.在初始和复发性CDI发作期间，在一些患者样本中报告了艰难梭菌菌株。然而，个别菌株的行为及其对症状性疾病的贡献尚不清楚。方法：采用体外人肠道模型研究两种不同的C。艰难梭菌菌株在初始和复发模拟CDI，以及他们对万古霉素治疗的反应。用混合的人粪便乳剂和固有的肠道微生物群C.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。艰难梭菌菌株响应于头孢曲松滴注而萌发和增殖，在高峰营养生长期间检测到细胞毒素。万古霉素滴注导致两种菌株的营养体迅速下降，开始给药后2天仅残留孢子。两种菌株的复发发生后，停止万古霉素安装，虽然这是更快地观察到，并在更大程度上，在一个菌株比其他。艰难梭菌菌株能够响应抗生素攻击（模拟CDI的开始）同时萌发和增殖。类似地，一种以上的菌株可以在模拟复发性CDI期间增殖，尽管在萌发和生长速率和时间上存在差异。在单个患者中，多种菌株可能导致CDI，可能对管理和细菌传播产生影响。
Background: 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.Methods: 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.Results: 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.Conclusions: 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.