What antibiotics are associated with Clostridioides difficile (C. diff) infection?

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Last updated: February 13, 2025View editorial policy

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From the Guidelines

Antibiotics associated with Clostridioides difficile (C. diff) infection include third-/fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin.

Key Points

  • The most important modifiable risk factor for the development of CDI is exposure to antibiotic agents, with virtually every antibiotic having been associated with CDI 1.
  • Certain classes of antibiotics, such as third-/fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin, have been found to be high risk for CDI 1.
  • 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.
  • The highest risk of CDI appears to be during and in the first month after antibiotic exposure, with a 7- to 10-fold increase in risk 1.
  • Both longer exposure to antibiotics and exposure to multiple antibiotics increase the risk for CDI 1.
  • Clindamycin, in particular, has been associated with a high risk of CDI, with a prospective study showing that administration of clindamycin resulted in diarrhea in 21% of patients and endoscopy-diagnosed pseudomembranous colitis in 10% 1.

Management

  • Minimizing the frequency and duration of high-risk antibiotic therapy and the number of antibiotic agents prescribed can help reduce CDI risk 1.
  • Implementing an antibiotic stewardship program and restricting the use of high-risk antibiotics, such as fluoroquinolones, clindamycin, and cephalosporins, can also help reduce CDI risk 1.

From the Research

Antibiotics Associated with C. diff Infection

The following antibiotics have been associated with an increased risk of Clostridioides difficile (C. diff) infection:

  • Clindamycin: strongly associated with C. diff infection, with an odds ratio (OR) of 20.43 2, 16.80 3, and 8.81 4
  • Fluoroquinolones: associated with C. diff infection, with an OR of 5.65 2, 5.50 3, and 4.05 4
  • Cephalosporins: associated with C. diff infection, with an OR of 4.47 2 and 5.68 3
  • Carbapenems: strongly associated with healthcare facility-associated C. diff infection, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing C. diff infection 5
  • Macrolides: associated with C. diff infection, with an OR of 2.55 2 and 2.65 3
  • Penicillins: associated with C. diff infection, with an OR of 3.25 2 and 2.71 3
  • Sulphonamides/trimethoprim: associated with C. diff infection, with an OR of 1.84 2 and 1.81 3
  • Cefdinir: associated with C. diff infection, with an adjusted odds ratio (aOR) of 5.86 4
  • Cefuroxime: associated with C. diff infection, with an aOR of 4.57 4
  • Nitrofurantoin: associated with C. diff infection, particularly in older patients with risk factors, with an aOR of 3.05 4

Variation in Risk

The risk of C. diff infection varies among different antibiotic classes, with some antibiotics posing a greater risk than others 2, 5, 6, 4, 3. Additionally, the risk of C. diff infection may vary depending on the specific population being studied, such as community-associated vs. healthcare facility-associated infections 2, 5.

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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