What is the risk of Clostridioides difficile (C. diff) associated with Cefepime (Cefepime)?

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From the Guidelines

Cefepime, a fourth-generation cephalosporin, is associated with a moderate-to-high risk of Clostridioides difficile (C. diff) infection, as it disrupts the normal gut microbiota, allowing C. diff to proliferate and produce toxins that damage the intestinal lining 1. The risk of C. diff infection with cefepime is significant, and patients taking this antibiotic should be monitored for symptoms of C. diff infection, including watery diarrhea, abdominal pain, fever, and in severe cases, signs of colitis.

  • Risk factors that increase the likelihood of developing C. diff while on cefepime include:
    • Advanced age (over 65)
    • Prolonged hospital stays
    • Immunosuppression
    • Previous C. diff infections
    • Concurrent use of proton pump inhibitors To minimize risk, cefepime should be prescribed only when clearly indicated, using the shortest effective duration possible, as the highest risk of CDI appears to be during and in the first month after antibiotic exposure 1.
  • Patients should be advised to report diarrhea that develops during or after antibiotic treatment, as prompt diagnosis and management of C. diff infection is essential to prevent complications, and antibiotic agents should be discontinued, if possible, in cases of suspected severe CDI 1. The use of cefepime should be carefully considered, and alternative antibiotics with a lower risk of CDI should be used when possible, to minimize the risk of C. diff infection and its associated morbidity and mortality 1.

From the FDA Drug Label

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. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

The risk of C. difficile associated diarrhea with Cefepime use is present, as it has been reported with nearly all antibacterial agents, including Cefepime. CDAD can range from mild diarrhea to fatal colitis, and it is essential to consider this condition in patients who present with diarrhea after antibiotic use 2.

From the Research

Cefepime and C. difficile Infection

  • Cefepime is a fourth-generation cephalosporin with a broad spectrum of antibacterial activity 3, 4.
  • The use of antibiotics, including cefepime, can disrupt the normal intestinal microbiota and increase the risk of Clostridioides difficile infection (CDI) 5, 6.
  • CDI is a major cause of diarrhea in both inpatients and outpatients, and is often associated with the use of antibiotics 5.
  • The treatment of CDI typically involves the use of vancomycin or fidaxomicin, and in some cases, fecal microbiota transplantation (FMT) may be considered 5, 6, 7.

Risk of C. difficile Infection with Cefepime

  • There is no direct evidence in the provided studies that specifically addresses the risk of C. difficile infection with cefepime.
  • However, it is known that the use of broad-spectrum antibiotics, including cephalosporins like cefepime, can increase the risk of CDI 5, 6.
  • The studies provided focus on the treatment of CDI and the use of cefepime as an antibiotic, but do not provide specific information on the risk of C. difficile infection associated with cefepime use 3, 5, 6, 7, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cefepime.

Pharmacotherapy, 1994

Research

Update of treatment algorithms for Clostridium difficile infection.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018

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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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