Diagnosing Clostridioides difficile Infection

By Kap Sum Foong, MD
Tufts Medical Center

"Dr. Foong, my patient developed new diarrhea while on antibiotics for community acquired pneumonia (CAP). Should this patient be tested for Clostridioides difficile?"

This is one of the most common questions that I get asked in my daily clinical practice as an infectious disease doctor.

Clostridioides difficile (also known as C. difficile) is a bacterium that causes diarrhea and colitis. Exposure to antibiotics is the single most important risk factor for C. difficile infection (CDI). Patients are 7 to 10 times more likely to get C. difficile infection while taking antibiotics and during the month after.

CDI is the most common healthcare-associated infection. Older patients and residents of long-term care facilities are at greater risk. More than 70% of long-term care residents received at least one course of antibiotic annually, and 40 to 70% of those prescriptions were inappropriate or not concordant with evidence-based guidelines.1

So, how do we diagnose CDI? Making the diagnosis of CDI is not as straightforward as just a positive stool C. difficile test. It requires two important components.

First, CDI should only be suspected if patients develop new diarrhea (≥3 loose stools in 24 hours) with relevant risk factors (e.g., recent antibiotic usage) and in the absence of alternative explanation (e.g., receipt of laxatives or new initiation on tube feeding).2

Second, it requires a positive stool test for toxigenic C. difficile organism or its toxin.3

The laboratory diagnostic approach to CDI is complex due to the wide array of available stool assays (e.g., NAAT, GDH, toxin A and B, culture) with varied sensitivity and specificity. These tests can be performed alone or in combination depending on the diagnostic algorithm of the institution.

Back to our patient. Let's say the primary hospitalist ordered a stool test for their patient with new diarrhea and CAP, and it comes back negative for C. difficile toxin but with a positive NAAT (PCR). However, the patient's diarrhea resolves the following day despite not being on anti-CDI treatment.

This is consistent with C. difficile colonization rather than CDI and, therefore, no CDI treatment was clinically indicated.

The primary hospitalist then reached out to me with a follow up question whether there is a role for secondary C. difficile prophylaxis while the patient is receiving systemic antibiotics for community acquired pneumonia.

This is an area of debate and active research, and the subject of a recent New England Journal of Medicine article. This practice is not currently recommended by the Infectious Diseases Society of America (IDSA), but we will need to stay tuned for more data from randomized controlled trials.


To learn more, please watch our "Office Hours" Webinar on Clostridioides difficile and Antimicrobial Stewardship 201 on March 21, 2023 from 12:00pm -1:00pm!


Check out the summarized IDSA guidance document for the diagnosis and treatment of CDI.

  1. Lim CJ et al. Clin Interv Aging. 2014;9:165-77.
  2. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):e1-e48.
  3. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994 Jan 27;330(4):257-62.