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

From the Guidelines

Clostridioides difficile (C. diff) infection risk factors include recent antibiotic use, particularly broad-spectrum agents such as fluoroquinolones (e.g., ciprofloxacin, levofloxacin), cephalosporins (e.g., ceftriaxone, cefepime), and clindamycin, with increased risk associated with longer durations of therapy (typically >3 days) and higher doses 1.

Key Risk Factors

• Advanced age (≥65 years) is a significant risk factor, potentially due to underlying comorbidities and increased exposure to healthcare settings 1.
• Underlying medical conditions, such as inflammatory bowel disease, gastrointestinal surgery, and immunocompromised states (e.g., chemotherapy, HIV/AIDS), also contribute to an increased risk of developing C. diff infection 1.
• Hospitalization and exposure to healthcare settings, particularly those with inadequate infection control practices, further elevate the risk of acquiring C. diff 1.
• Immunocompromised patients, including those with HIV/AIDS, solid organ transplant recipients, and cancer patients, are at higher risk due to ongoing immunosuppression and antibiotic use 1.
• Other risk factors include gastrointestinal surgery, tube feeding, and low serum albumin level 1.

Antibiotic-Associated Risk

• Antibiotic exposure is a significant risk factor, with certain classes (e.g., third-/fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin) being high-risk 1.
• Duration and dose of antibiotic therapy also impact the risk of C. diff infection, with longer durations and higher doses increasing the risk 1.

From the FDA Drug Label

WARNING Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin hydrochloride and may range in severity from mild diarrhea to fatal colitis. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefepime for injection, and may range in severity from mild diarrhea to fatal colitis.

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

• Use of antibacterial agents, as they alter the normal flora of the colon, leading to overgrowth of C. difficile 2 3
• Hypertoxin-producing strains of C. difficile, which cause increased morbidity and mortality 2 3
• Prolonged antibiotic use, as CDAD can occur over two months after the administration of antibacterial agents 2 3
• Renal impairment, as high and prolonged serum antibiotic concentrations can occur in patients with renal impairment 3

From the Research

Risk Factors for Clostridioides difficile (C. diff) Infection

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

• Prior antibiotic use, which is the dominant risk factor, with the odds of subsequent CDI increasing by 12.8% for every antibiotic day of therapy prior to the index admission 4
• Specific antibiotics, such as:
  • Second-generation and later cephalosporins, especially oral 4
  • Carbapenems 4, 5, 6
  • Fluoroquinolones 4, 7, 8, 6
  • Clindamycin 4, 7, 8, 6
  • Lincosamides, such as clindamycin, which had the greatest proportion of CDI reports 6
• Duration of antibiotic exposure, with longer courses associated with increased risk 7, 5
• Age, with older patients having a higher risk of CDI 8
• Comorbidities, such as prior emergency department or acute care stay, Charlson comorbidity index, and functional status 7

Antibiotic-Specific Risks

The risks associated with specific antibiotics vary, with some antibiotics conferring a higher risk of CDI than others. For example:

• Clindamycin was associated with the greatest CA-CDI risk, overall 8
• Cefdinir, cefuroxime, and fluoroquinolones were also associated with a high risk of CA-CDI 8
• Nitrofurantoin was associated with CA-CDI, especially in older patients with CA-CDI risk factors 8
• Doxycycline was used as a reference comparison and was associated with a lower risk of CDI 8