What percentage of patients develop Clostridioides difficile (C. difficile) infection when taking clindamycin?

Risk of Clostridium difficile Infection with Clindamycin

Approximately 10-21% of patients taking clindamycin develop Clostridioides difficile infection (CDI), with 10% developing pseudomembranous colitis as demonstrated in landmark studies. 1

Clindamycin as a High-Risk Antibiotic for CDI

Clindamycin is one of the antibiotics most strongly associated with CDI development due to its significant disruption of normal gut flora. The evidence clearly shows:

• In the landmark 1974 Tedesco study, clindamycin administration resulted in diarrhea in 21% of patients, with 10% developing pseudomembranous colitis confirmed by endoscopy 1
• Clindamycin has one of the highest odds ratios for CDI development among all antibiotics, ranging from 2.12-42 according to systematic reviews 1
• In a case-control study of community-acquired CDI, clindamycin exposure had an adjusted matched odds ratio of 35.31 (95% CI 4.01-311.14), which was higher than other high-risk antibiotics 1

Mechanism of Clindamycin-Associated CDI

The pathophysiology involves:

• Disruption of normal gut microbiota, which normally provides colonization resistance against C. difficile 1
• Loss of protective gut flora allows C. difficile to proliferate and produce toxins 1
• Clindamycin resistance is common among C. difficile strains (59% weighted pooled resistance), which gives these strains a selective advantage when clindamycin is used 2

Risk Factors That May Increase CDI Risk with Clindamycin

Several factors can increase the risk of developing CDI when taking clindamycin:

• Age >65 years 1
• Prolonged hospital stay 1
• Concurrent use of proton pump inhibitors 1
• Inflammatory bowel disease 1
• Chronic kidney disease 1
• Immunocompromised status 1
• Previous hospitalization 1

Evidence from Outbreak Investigations

Multiple studies have documented clindamycin's role in CDI outbreaks:

• Hospital outbreaks of CDI have been directly linked to increased clindamycin use 3
• Restricting clindamycin use in hospitals has been shown to dramatically reduce CDI rates:
  • One study showed a reduction from 11.5 cases/month to 3.33 cases/month after clindamycin restriction 4
  • Another investigation showed that restricting clindamycin led to a prompt decrease in infection rates 5

Clinical Implications

When prescribing clindamycin, clinicians should:

• Consider the high risk of CDI (10-21% of patients) when deciding if clindamycin is necessary
• Use alternative antibiotics when possible, especially in high-risk patients
• Discontinue clindamycin promptly when no longer needed
• Monitor for symptoms of CDI (diarrhea, abdominal pain, fever) during and after treatment
• Be aware that CDI can develop up to one month after clindamycin discontinuation 1

Prevention Strategies

To reduce the risk of clindamycin-associated CDI:

• Implement antimicrobial stewardship programs that restrict clindamycin use 5, 4
• Consider alternative antibiotics with lower CDI risk when appropriate
• Avoid unnecessary proton pump inhibitors in patients receiving clindamycin 1
• Use the shortest effective duration of clindamycin therapy

The high rate of CDI associated with clindamycin (10-21%) should prompt careful consideration before prescribing this antibiotic, particularly in patients with additional risk factors for CDI.