Is the patient's diarrhea caused by Clostridioides difficile (C-Diff) infection or antibiotic-associated diarrhea?

From the Guidelines

To determine if a patient's diarrhea is caused by Clostridioides difficile (C. diff) infection or antibiotic use, testing for C. diff toxins is essential, and a diagnosis of C. diff requires acute-onset, clinically significant, new-onset diarrhea and highly sensitive testing, such as nucleic acid amplification or glutamate dehydrogenase, in combination with highly specific testing, such as toxin enzyme immunoassay, as recommended by the AGA in 2024 1. The diagnosis of C. diff infection should be considered in patients with diarrhea occurring in hospitals, particularly if the patient has received antibiotics within the previous 30 days, as stated in the 2009 guidelines by the Infectious Diseases Society of America 1. Some key points to consider when evaluating a patient's diarrhea include:

• The presence of watery, foul-smelling stool, abdominal pain, fever, and sometimes blood in the stool, which are distinctive features of C. diff diarrhea
• The timing of the diarrhea, as C. diff can occur during antibiotic treatment but often appears 1-10 days after completing antibiotics, while simple antibiotic-associated diarrhea typically begins during treatment
• The use of antibiotics, particularly clindamycin, fluoroquinolones, cephalosporins, or penicillins, which are commonly associated with C. diff infection
• The patient's clinical history and risk factors for C. diff infection, such as recent hospitalization, use of multiple antibiotic classes, and duration of exposure If C. diff is confirmed, treatment with oral vancomycin, fidaxomicin, or metronidazole should be initiated while discontinuing the offending antibiotic if possible, as recommended by the 2017 update by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America 1. It is also important to note that the evidence base to optimize C. diff testing is weak, and clinical criteria for the diagnosis of C. diff have altered over time, with the number and frequency of diarrheal stools required to justify C. diff testing declining over the past 40 years, as discussed in the 2018 guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America 1. In addition, laboratories can improve specificity by rejecting specimens that are not liquid or soft, and clinicians can improve laboratory test relevance by only testing patients likely to have C. diff disease, as recommended by the 2018 guidelines 1. Overall, a comprehensive approach to diagnosing and managing C. diff infection is essential to improve patient outcomes and reduce the risk of transmission.

From the FDA Drug Label

5.6 Development of Drug-Resistant Bacteria 6.1 Clinical Trials Experience 14.1 Diarrhea Associated with Clostridium difficile

The patient is taking vancomycin (PO) for Clostridium difficile (C-Diff) associated diarrhea. To determine if the patient's diarrhea is caused by C-Diff or the antibiotics, consider the following:

• C-Diff diarrhea is typically characterized by watery stools, abdominal cramping, and fever.
• Antibiotic-associated diarrhea can also present with watery stools and abdominal cramping, but may not always be accompanied by fever. Since the vancomycin label does not provide explicit guidance on differentiating between C-Diff and antibiotic-associated diarrhea, a conservative clinical decision would be to monitor the patient's symptoms and stool test results to determine the cause of diarrhea 2.

From the Research

Determining the Cause of Diarrhea

To determine if a patient is having diarrhea from C-Diff or if the antibiotics they are on are causing diarrhea, consider the following:

• The patient's medical history, including recent antibiotic use and hospitalization
• The presence of other symptoms, such as fever, abdominal pain, and blood in the stool
• Laboratory test results, including stool tests for C. difficile toxins and other pathogens

Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic use, and can be caused by multiple organisms, including C. difficile, C. perfringens, S. aureus, and Candida 3. Some antibiotics, such as erythromycin and the penicillin class, are more likely to cause non-C. difficile AAD.

C. difficile Infection

C. difficile infection (CDI) is a leading cause of antibiotic-associated diarrhea, and can range from mild to severe, life-threatening colitis 4. The diagnosis of CDI is based on direct detection of C. difficile toxins in feces, and treatment options include vancomycin, fidaxomicin, and metronidazole, although metronidazole is considered inferior 4, 5.

Distinguishing between AAD and CDI

To distinguish between AAD and CDI, consider the following:

• The timing of the diarrhea in relation to antibiotic use
• The presence of other symptoms, such as fever and abdominal pain
• Laboratory test results, including stool tests for C. difficile toxins and other pathogens
• The patient's response to treatment, including the use of probiotics or fecal microbiota transplantation 3, 6, 7

Treatment and Prevention

Treatment options for AAD and CDI include antibiotics, such as vancomycin and fidaxomicin, and fecal microbiota transplantation 6, 7, 5. Prevention strategies include antibiotic stewardship, infection control measures, and the use of probiotics to reduce the risk of AAD 3, 5.