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

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Last updated: June 5, 2025View editorial policy

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From the Guidelines

The main risk factors for Clostridioides difficile (C. diff) infection include recent antibiotic use, hospitalization, advanced age (over 65), immunocompromised status, and gastrointestinal surgery or procedures. These risk factors are supported by the most recent and highest quality study available, which highlights the importance of antibiotic exposure, particularly broad-spectrum antibiotics like fluoroquinolones, clindamycin, cephalosporins, and penicillins, in disrupting the normal gut microbiota and allowing C. diff to proliferate 1.

Some key points to consider:

  • Healthcare exposure is significant because C. diff forms spores that can survive on surfaces for months and resist standard cleaning agents.
  • Elderly patients are at higher risk due to age-related changes in gut microbiota, comorbidities, and frequent healthcare exposure.
  • Immunosuppression from conditions like HIV, cancer, or medications such as chemotherapy agents or corticosteroids reduces the body's ability to resist infection.
  • Gastrointestinal procedures like endoscopy can introduce spores directly into the gut.
  • Additional risk factors include inflammatory bowel disease, proton pump inhibitor use, and prior C. diff infection.

Understanding these risk factors is crucial for identifying vulnerable patients who may benefit from preventive measures like antimicrobial stewardship and enhanced infection control practices, as recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) 1.

Key considerations for prevention and management include:

  • Discontinuing antibiotic use when possible, especially in cases of suspected severe C. diff infection.
  • Using antimicrobial therapy with agents that are less frequently implicated in antibiotic-associated C. diff infection, such as parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline.
  • Implementing infection control practices, including hand hygiene with soap and water, and the use of contact precautions and good cleaning and disinfection of the environment and patient equipment.

From the Research

Risk Factors for C diff Infection

The risk factors for Clostridioides difficile (C diff) infection include:

  • Antibiotic exposure, which is the most important modifiable risk factor, with the risk being dose-related and higher with longer courses and combination therapy 2
  • Older age 2
  • Recent hospitalization 2
  • Multiple comorbidities 2
  • Use of gastric acid blockers 2
  • Inflammatory bowel disease 2
  • Immunosuppression 2
  • Exposure to health care facilities 3
  • Certain antibiotics, such as second-generation and later cephalosporins, carbapenems, fluoroquinolones, and clindamycin, which carry a higher risk of CDI 4
  • Cumulative antibiotic exposure prior to admission, which is the greatest contributor to the risk of subsequent CDI 4

Patient Populations at Risk

C diff infection can affect various patient populations, including:

  • Older adults 2
  • Patients with multiple comorbidities 2
  • Patients with inflammatory bowel disease 2
  • Immunocompromised patients 2
  • Patients who have been recently hospitalized 2
  • Patients who have been exposed to health care facilities 3
  • Patients who have taken certain antibiotics, such as clindamycin 3

Prevention and Management

Prevention and management of C diff infection involve:

  • Responsible antibiotic prescribing 2
  • Vigilant handwashing, with soap and water being superior to alcohol-based products during outbreaks 3
  • Discontinuing the contributing antibiotic, if possible 2
  • Treatment with oral vancomycin or oral fidaxomicin for initial episodes of nonsevere C diff infection 3
  • Fecal microbiota transplantation as a reasonable treatment option for patients with multiple recurrent episodes 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Common questions about Clostridium difficile infection.

American family physician, 2014

Research

Clostridioides difficile Infection: Update on Management.

American family physician, 2020

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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