What is the percentage risk of Clostridioides difficile (C. difficile) infection with cephalosporins (antibiotics) and clindamycin (antibiotic)?

Risk of C. difficile Infection with Cephalosporins and Clindamycin

Clindamycin poses the highest risk for C. difficile infection with an adjusted matched odds ratio of 35.31, while cephalosporins carry a significant risk with an odds ratio of 19.02 for community-associated infections. 1

Specific Risk Percentages by Antibiotic Class

Clindamycin

• Highest risk antibiotic for CDI development
• Adjusted matched odds ratio (AmOR): 35.31 (95% CI 4.01-311.14) 1
• Historical data shows approximately 21% of patients receiving clindamycin develop diarrhea, with 10% developing pseudomembranous colitis 1
• 67% of C. difficile strains show resistance to clindamycin (MIC ≥8 μg/ml) 2

Cephalosporins

• Third/fourth-generation cephalosporins are among the highest risk antibiotics 1
• Community-associated CDI risk:
  • Cephalosporins: AmOR 19.02 (95% CI 1.13-321.39) 1
• Hospital-associated CDI risk by generation:
  • Third-generation: OR 3.20 (95% CI 1.80-5.71) 3
  • Second-generation: OR 2.23 (95% CI 1.47-3.37) 3
  • Fourth-generation: OR 2.14 (95% CI 1.30-3.52) 3
• Hospitals that decreased cephalosporin use by ≥20% saw a 13% decrease in hospital-onset CDI 4

Risk Factors That Amplify CDI Risk

The risk of developing CDI is significantly increased when the following factors are present alongside antibiotic exposure:

1. Host factors 1:

   • Age >65 years
   • Comorbidities (especially IBD, chronic kidney disease)
   • Immunodeficiency
   • Malnutrition
   • Low serum albumin

2. Healthcare exposure factors:

   • Recent hospitalization
   • Long-term care facility residence
   • Emergency department visits (AmOR 17.37) 1

3. Medication-related factors:

   • Proton pump inhibitors (PPI) use 1
   • Multiple antibiotic exposure 1
   • Longer duration of antibiotic therapy 1

Mechanism of Risk

Antibiotics like clindamycin and cephalosporins disrupt the normal gut microbiota, creating an environment where C. difficile can proliferate and produce toxins 1. The risk of CDI is increased up to sixfold during antibiotic therapy and in the month following cessation 1.

Time Course of Risk

• Highest risk period: During antibiotic therapy and within the first month after exposure (7-10 fold increase) 1
• Risk remains elevated for up to 3 months after antibiotic cessation 1
• Even single-dose surgical antibiotic prophylaxis increases CDI risk 1

Clinical Implications and Prevention

1. Antibiotic stewardship is critical:

   • Hospitals that decreased total antibiotic use by ≥30% saw a 33% decrease in hospital-onset CDI 4
   • Avoid unnecessary use of high-risk antibiotics, particularly clindamycin and cephalosporins

2. Consider alternative antibiotics when possible:

   • Tetracyclines have not been associated with increased CDI risk (OR 0.91) 5
   • Macrolides, sulfonamides, and aminoglycosides have lower association with CDI 1, 5

3. Discontinue unnecessary antibiotics promptly in patients at high risk for CDI 1

4. Reassess need for PPIs in patients receiving antibiotics, as they may increase risk of CDI 1

Caveat

The wide confidence intervals in some studies indicate considerable uncertainty in the precise magnitude of risk. Additionally, risk varies based on local C. difficile strain prevalence, particularly with fluoroquinolone-resistant epidemic strains 1. The risk percentages should be interpreted within the clinical context of the individual patient's risk factors.