Dysbiosis and C. Diff Infection Phase 2

DYSBIOSIS AND RECURRENT
C. DIFFICILE INFECTION

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  1. Importance of Microbial Diversity
  2. Dysbiosis and Recurrent C. difficile Infection
  3. Currently Approved Treatment Options
  4. Historic Microbiome Restoration Approaches
  5. Patient and Healthcare Burdens

C. difficile may proliferate as a result of dysbiosis

 

Dysbiosis creates an insufficiency of Bacteroidetes and Firmicutes, which may lead to an environment suited for the growth of C. difficile infection (CDI).1,2

Dysbiosis is the disruption of the volume and diversity of the gut microbiome. This may be attributed to factors including stress, diet, hygiene, and antibiotic use. Dysbiosis is associated with a range of gastrointestinal (GI) and non-GI diseases including neurologic, metabolic, liver, inflammatory, and infectious diseases.1,3,4

The gut microbiota generally play a role in colonization resistance by which the native organisms prevent pathogenic microbes from flourishing. Disruption of the gut microbiome leads to an environment suited for the proliferation of C. difficile.1,2

When the relationship between the gut and its healthy flora becomes imbalanced, dysbiosis results. This leads to an intestinal microenvironment susceptible to pathogenic insult from opportunistic bacteria, such as CDI—capable of causing a wide spectrum of symptoms ranging from mild diarrhea to sepsis to mortality.1

Typically, antibiotic use treats the acute infection. However, antibiotics do not restore the microbiome, potentially increasing the risk of recurrence.5 Thus starts a vicious cycle.

Image showing how the C. Difficile infection can be a vicious cycle, from healthy microbiome to C. Difficile proliferates to antibiotic treatment to recurrence

For illustrative purposes.

aRisk of recurrence is highest in the 3-month period following antibiotic treatment of index CDI.11

Restoring a gut microbiome—disrupted by CDI—may be a promising option
for reducing recurrence.12

CURRENTLY APPROVED TREATMENTS
C. Difficile infection an Urgent public health threat 30,000 annual mortality

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References

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  2. Staley C, Khoruts A, Sadowsky MJ. Contemporary applications of fecal microbiota transplantation to treat intestinal diseases in humans. Arch Med Res. 2017;48(8):766-773.
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  9. Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(suppl 6):21-27.
  10. Smits WK, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020.
  11. Hensgens MPM, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67(3):742-748.
  12. Wilcox MH, McGovern BH, Hecht GA. The efficacy and safety of fecal microbiota transplant for recurrent Clostridium difficile infection: current understanding and gap analysis. Open Forum Infect Dis. 2022;7(5):ofaa114.