What causes pseudomembranous colitis, also known as Clostridioides difficile (C. difficile) infection?

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Last updated: March 28, 2025View editorial policy

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From the Guidelines

Pseudomembranous colitis, also known as Clostridioides difficile (C. difficile) infection, is primarily caused by the disruption of normal gut microbiota due to antibiotic use, with the most recent and highest quality evidence suggesting that antibiotics such as clindamycin, fluoroquinolones, cephalosporins, and penicillins are most commonly associated with this condition 1. The main risk factors for C. difficile infection can be divided into three general categories: host factors, exposure to C. difficile spores, and factors that disrupt the normal colonic microbiome, with antibiotic exposure being the central factor in the pathogenesis of CDI 1.

  • Key risk factors include:
    • Advanced age
    • Hospitalization
    • Immunocompromised state
    • Gastrointestinal surgery
    • Use of certain antibiotics, such as clindamycin, fluoroquinolones, cephalosporins, and penicillins
    • Use of proton pump inhibitors (PPIs), although the evidence for this is still controversial 1 The disruption of the intestinal microbiota by antibiotics allows C. difficile bacteria to proliferate and produce toxins that damage the intestinal lining, causing inflammation and the formation of characteristic yellowish-white plaques or "pseudomembranes" on the colon surface 1. The most effective way to prevent C. difficile transmission is through hand hygiene with soap and water, use of contact precautions, and good cleaning and disinfection of the environment and patient equipment 1. In cases of suspected severe CDI, antibiotic agents should be discontinued if possible, and antimicrobial therapy with agents that are less frequently implicated with antibiotic-associated CDI should be used 1. Treatment typically involves stopping the offending antibiotic if possible and administering specific antibiotics effective against C. difficile, such as oral vancomycin, fidaxomicin, or metronidazole 1. Severe or recurrent cases may require longer treatment courses, fecal microbiota transplantation, or other interventions, and the condition can be life-threatening if not promptly diagnosed and treated, potentially leading to toxic megacolon, perforation, or sepsis 1.

From the Research

Causes of Pseudomembranous Colitis

  • Pseudomembranous colitis, also known as Clostridioides difficile (C. difficile) infection, is caused by the overgrowth of C. difficile in the gastrointestinal tract, often as a result of antibiotic therapy that alters the fecal flora 2, 3.
  • The use of broad-spectrum antibiotics can lead to the disruption of the normal gut microbiota, allowing C. difficile to overgrow and produce toxins 4, 3.
  • C. difficile infection can occur in anyone who develops diarrhea during or after antibiotic therapy, and it is a considerable clinical concern due to its severity, increasing frequency, complications, and development of antibiotic-resistant organisms 2.

Risk Factors

  • Antibiotic therapy is a major risk factor for developing C. difficile infection, as it can disrupt the normal balance of the gut microbiota 2, 3.
  • Other risk factors include hospitalization, advanced age, and underlying medical conditions 2.
  • The use of non-CDI antibiotics can also predict repeat fecal microbiota transplantation (FMT) in patients with severe or severe-complicated C. difficile infection 5.

Underlying Mechanisms

  • The exact mechanisms of C. difficile infection are not fully understood, but it is thought that the disruption of the normal gut microbiota allows C. difficile to overgrow and produce toxins 3.
  • The toxins produced by C. difficile can cause inflammation and damage to the lining of the colon, leading to symptoms such as diarrhea, abdominal pain, and fever 2, 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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