Models for the study of Clostridium difficile infection

  title={Models for the study of Clostridium difficile infection},
  author={Emma L. Best and Jane Freeman and Mark H. Wilcox},
  journal={Gut Microbes},
  pages={145 - 167}
Models of Clostridium difficile infection (C. difficile) have been used extensively for Clostridium difficile (C. difficile) research. The hamster model of C. difficile infection has been most extensively employed for the study of C. difficile and this has been used in many different areas of research, including the induction of C. difficile, the testing of new treatments, population dynamics and characterization of virulence. Investigations using in vitro models for C. difficile introduced the… 
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This review summarises key aspects of the small animal models currently used in C. difficile studies with a specific focus on major differences between them and highlights the advantages and disadvantages of each model.
Murine models to study Clostridium difficile infection and transmission.
Mixed infection by Clostridium difficile in an in vitro model of the human gut.
Data suggest that multiple C. difficile strains are able to proliferate concurrently in an in vitro model reflective of the human colon, which augments recent human epidemiological studies in this area.
Predictive values of models of Clostridium difficile infection.
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An integrated understanding of the timing and location of the events surrounding C. difficile colonization is provided and potential targets for the development of new therapeutic strategies are identified.
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The current drug discovery pipeline is reviewed, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.
Successional Dynamics in the Gut Microbiome Determine the Success of Clostridium difficile Infection in Adult Pig Models
The observed community patterns suggest that successional dynamics following antibiotic treatment facilitate C. difficile establishment, and the similarities between the microbiome responses observed in this study and those reported in CDI-infected humans further support the utility of adult pigs as models for the study of CDI.


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Comparison with the results of a previous gut model study showed that vancomycin was more effective than metronidazole in reducing C. difficile PCR ribotypes numbers and cytotoxin titres, possibly correlating with the extent of germination capacity.
A mouse model of Clostridium difficile-associated disease.
A mouse model of antibiotic-induced C. difficile-associated disease (CDAD) that more closely resembles human disease is developed and will be valuable in testing new treatments, examining disease pathogenesis, and elucidating mechanisms of protective immunity.
Evaluation of linezolid for the treatment of Clostridium difficile infection caused by epidemic strains using an in vitro human gut model.
In a gut model that simulates CDI, linezolid reduced the duration of cytotoxin production by C. difficile PCR ribotype 027 without influencing viable counts of vegetative forms of the organism and may reduce toxin levels, as reported in staphylococci and streptococci.
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Studies suggest that asymptomatic colonization with Clostridium difficile (CD) decreases the risk of CD-associated disease (CDAD) in humans. A hamster model was used to test the efficacy of
Tigecycline does not induce proliferation or cytotoxin production by epidemic Clostridium difficile strains in a human gut model.
Tigecycline exposure did not induce C. difficile proliferation or cytotoxin production despite reduced competing microflora, and factors other than gut microfloras colonization resistance may contribute to the low risk of CDI induction.
The role of toxin A and toxin B in Clostridium difficile infection
It is shown that isogenic mutants of C. difficile producing either toxin A or toxin B alone can cause fulminant disease in the hamster model of infection, re-establish the importance of both toxin A and toxin B and highlight the need to continue to consider both toxins in the development of diagnostic tests and effective countermeasures against C. diffuse.
Tigecycline Exhibits Inhibitory Activity against Clostridium difficile in the Colon of Mice and Does Not Promote Growth or Toxin Production
Tigecycline did not promote the establishment of colonization in mice, yet it did not reduce concentrations of C. difficile, probably due to inhibitory activity against C.difficile and relative sparing of indigenous anaerobic microflora.
Antagonism of toxigenic Clostridium difficile by nontoxigenic C. difficile.
Simultaneous administration of nontoxigenic and toxigenic C. difficile did not lead to suppression of toxigenics C.difficile and conferred no protection, in keeping with previously established concepts of bacterial interactions on body surfaces.