What are the risk factors for Clostridium difficile (C. diff) infection?

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Last updated: April 20, 2025View editorial policy

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From the Guidelines

The main risk factors for Clostridium difficile infection include recent antibiotic use, hospitalization, advanced age, and immunocompromised status, with antibiotics being the most important modifiable risk factor. According to the 2018 clinical practice guidelines for Clostridium difficile infection in adults and children by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1, advanced age and duration of hospitalization are significant risk factors, with the daily increase in risk of C. difficile acquisition during hospitalization suggesting that duration of hospitalization may be a proxy for exposure to the organism, likelihood of exposure to antibiotics, and severity of underlying illness. The guidelines also highlight that virtually every antibiotic has been associated with CDI, but certain classes like third-/fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin have been found to be high risk.

Some key points to consider:

  • The disruption of the intestinal microbiota by antibiotics is long-lasting, and the risk of CDI increases both during therapy and in the 3-month period following cessation of therapy 1.
  • Cancer chemotherapy is another risk factor for CDI, mediated by the antibiotic activity of several chemotherapeutic agents and immunosuppressive effects of neutropenia 1.
  • Other risk factors include gastrointestinal surgery, inflammatory bowel disease, and previous C. difficile infection.
  • Patients with comorbidities like chronic kidney disease or cancer face higher risks.
  • A 2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients also found that antibiotic exposure, emergency department visit, white race, cardiac disease, chronic kidney disease, and inflammatory bowel disease were associated with community-acquired CDI 1.

In terms of prevention strategies, proper hand hygiene with soap and water, contact precautions for infected patients, environmental cleaning with sporicidal agents, and antibiotic stewardship to minimize unnecessary antibiotic use are crucial. Additionally, understanding the role of medications like proton pump inhibitors in the pathogenesis of CDI remains elusive, and more careful assessment of confounding factors, symptoms, and criteria for testing for recurrence is needed 1.

From the Research

Risk Factors for Clostridium Difficile Infection

  • Antibiotic exposure is a major modifiable risk factor for C. difficile infection, with the risk being dose-related and higher with longer courses and combination therapy 2, 3
  • Older age is a significant risk factor for C. difficile infection 2, 3, 4, 5
  • Recent hospitalization is a risk factor for C. difficile infection 2
  • Multiple comorbidities, such as diabetes mellitus, inflammatory bowel disease, and end-stage renal disease, increase the risk of C. difficile infection 2, 3, 4
  • Use of gastric acid blockers, such as proton pump inhibitors, is a risk factor for C. difficile infection 2, 6
  • Immunosuppression is a risk factor for C. difficile infection 2, 5
  • Infection with a hypervirulent strain of C. difficile is a risk factor for recurrent C. difficile infection 4

Specific Antibiotics Associated with C. difficile Infection

  • Cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam are associated with a higher risk of C. difficile infection 3
  • The "4C" antibiotics (clindamycin, cephalosporins, co-amoxiclav, and ciprofloxacin) are associated with a higher risk of C. difficile infection 6

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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