What is the likelihood of developing Clostridioides difficile (C. diff) infection after prolonged use of amoxicillin (amoxicillin)?

From the Guidelines

The risk of developing Clostridioides difficile (C. diff) infection after taking amoxicillin for an extended period is relatively low but real, with the highest risk appearing during and in the first month after antibiotic exposure 1.

Risk Factors

The development of C. diff infection is influenced by various factors, including:

• Host factors such as immune status, co-morbidities, and age more than 65 years 1
• Exposure to C. difficile spores through hospitalizations, community sources, or long-term care facilities 1
• Factors that disrupt the normal colonic microbiome, such as antibiotics, other medications, and surgery 1

Antibiotic-Associated Risk

Amoxicillin, a penicillin, is considered to be at moderate risk for CDI, although the risk is generally lower compared to other antibiotics like clindamycin, third-generation cephalosporins, and fluoroquinolones 1.

Reducing Risk

To minimize the risk of C. diff infection while taking amoxicillin:

• Complete the full prescribed course and take it exactly as directed
• Consider probiotics, but discuss this with your healthcare provider first
• Watch for symptoms like watery diarrhea, abdominal pain, fever, or blood in stool during or after antibiotic treatment, and seek medical attention promptly if these develop
• Practice proper hand hygiene to prevent C. diff transmission 1

Important Considerations

It is essential to note that the risk of CDI increases with longer exposure to antibiotics and that even limited exposure, such as single-dose surgical antibiotic prophylaxis, can increase a patient's risk of C. difficile colonization and symptomatic disease 1.

Guidance

Given the potential risks, it is crucial to weigh the benefits and risks of antibiotic use, particularly in vulnerable populations, and to consider alternative treatments or prophylactic measures when possible 1.

From the FDA Drug Label

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin, and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibacterial use Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

The likelihood of developing Clostridioides difficile (C. diff) infection after prolonged use of amoxicillin is a potential risk, as CDAD has been reported with the use of nearly all antibacterial agents, including amoxicillin. However, the exact likelihood is not specified in the drug label.

• Key points:
  • CDAD can range from mild diarrhea to fatal colitis
  • CDAD can occur over 2 months after amoxicillin administration
  • Careful medical history is necessary to consider CDAD in patients with diarrhea after amoxicillin use 2

From the Research

Likelihood of Developing C. diff Infection after Prolonged Use of Amoxicillin

• The likelihood of developing Clostridioides difficile (C. diff) infection after prolonged use of amoxicillin is a significant concern, as antibiotic use is the strongest modifiable risk factor for the development of C. diff infection 3.
• A longitudinal case-cohort study found that longer antibiotic duration was associated with increased risk of C. diff infection, with 10- and 14-day courses incurring 12% and 27% more risk compared to 7-day courses, respectively 3.
• Among 7-day courses with similar indications, moxifloxacin resulted in 121% more risk than amoxicillin, while clindamycin resulted in 112% more risk than cloxacillin 3.
• The risk of C. diff infection associated with amoxicillin use is lower compared to other antibiotics such as moxifloxacin and clindamycin, but still significant 3.

Comparative Risks of C. diff Infection

• A study comparing the efficacy of interventions designed to prevent recurrent C. diff infection found that fidaxomicin and fecal microbiota transplantation (FMT) were effective in preventing recurrence 4.
• The study also found that monoclonal antibodies, such as actoxumab and bezlotoxumab, were effective in preventing recurrence, especially when used in combination 4.
• Prebiotics, probiotics, and non-antibiotic polymers, such as oligofructose and Saccharomyces boulardii, also showed promise in preventing recurrence 4.

Management of C. diff Infection

• The management of C. diff infection involves a range of treatments, including antibiotics, FMT, and monoclonal antibodies 5, 6, 7.
• Fidaxomicin and vancomycin are commonly used antibiotics for the treatment of C. diff infection, while FMT is used for recurrent cases 5, 6, 7.
• Monoclonal antibodies, such as bezlotoxumab, are also used to reduce recurrence rates in high-risk patients 5, 6.