Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Department of Microbiology, PathWest Laboratory Medicine; School of Medical and Health Sciences, Edith Cowan University; School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia.
J Infect. 2018 Nov;77(5):417-426. doi: 10.1016/j.jinf.2018.06.006. Epub 2018 Jun 30.
Antibiotic-associated diarrhoea (AAD) caused by C. difficile is one of the most common nosocomial infections, however, little is known about infections related to antimicrobial use for pathogens other than C. difficile. We therefore aimed to provide insight into other bacterial causes of AAD, and how infection with these pathogens causes damage in the dysbiotic gut.
Clinical isolates from C. difficile-negative AAD patients were whole genome sequenced for in silico analysis of potential virulence factors and antimicrobial resistance determinants. A mouse model of infection was developed to assess the capacity of these isolates to cause gastrointestinal damage, which was analysed by studying specific markers in the gastrointestinal mucosa of infected mice.
Several bacterial pathogens were isolated from patients with C. difficile-negative AAD. Each isolate showed the potential for virulence based on encoded virulence factors, as well as most showing antimicrobial resistance in vitro. Isolates of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were tested in the mouse model of infection, inducing damage primarily in the small intestine, affecting adherens junction integrity, cellular polarity, and cellular proliferation.
Several pathogens of clinical importance other than C. difficile are able to cause gastrointestinal infection following antimicrobial-mediated dysbiosis. The virulence potential and multidrug resistance identified in these isolates illuminates the importance of further diagnostic screening in cases of C. difficile-negative AAD.
艰难梭菌（C. difficile）引起的抗生素相关性腹泻（AAD）是最常见的医院获得性感染之一，但对于除艰难梭菌以外的抗菌药物相关病原体引起的感染知之甚少。因此，本研究旨在深入了解其他导致 AAD 的细菌病原体，以及这些病原体如何在肠道菌群失调的情况下引起损伤。
对艰难梭菌阴性 AAD 患者的临床分离株进行全基因组测序，进行潜在毒力因子和抗菌药物耐药性决定因素的计算机分析。建立了感染模型以评估这些分离株引起胃肠道损伤的能力，通过研究感染小鼠胃肠道黏膜中的特定标志物来分析感染情况。
从艰难梭菌阴性 AAD 患者中分离出了几种细菌病原体。每个分离株都基于编码的毒力因子显示出潜在的毒力，并且大多数在体外显示出抗菌药物耐药性。对大肠杆菌、铜绿假单胞菌和肺炎克雷伯菌的分离株进行了感染小鼠模型的测试，主要在小肠中引起损伤，影响黏着连接的完整性、细胞极性和细胞增殖。
除艰难梭菌以外，还有几种具有临床重要性的病原体能够在抗菌药物介导的肠道菌群失调后引起胃肠道感染。这些分离株的毒力潜力和多药耐药性表明，在艰难梭菌阴性 AAD 病例中需要进一步进行诊断性筛查。
