Clostridium difficile—To Test or Not to Test? Response to Kundrapu et al

To the Editor—While the laboratory diagnosis of Clostridium difficile infection (CDI) has been a subject of much discussion in recent years, the exact criteria to decide which specimens to test are less debated. Kundrapu et al ¹ call for laboratories using stand-alone nucleic acid amplification tests for C. difficile testing to reduce testing of specimens that fail to meet clinical criteria, specifically patients with diarrhea without recent antibiotic exposure. In their study, a patient did not meet clinical criteria for testing if they had <3 unformed stools within 24 hours. We caution against this approach because it may delay implementation of infection prevention and control precautions. In addition, the potential for confusion exists between the criteria for laboratory testing of a diarrheal specimen and the definition of a clinical case of CDI.

The guidelines from the American Society for Microbiology ² recommend that toxigenic C. difficile testing be limited to patients with ≥3 unformed stool specimens in a 24- hour period unless ileus is suspected. This recommendation contrasts with other international CDI guidelines, and the reasoning behind this difference is unclear. European guidelines recommend testing unformed stool of patients with potential infective diarrhea and negative tests for common enteropathogens, irrespective of a number of factors, including antibiotic use. ³ Irish ⁴ and UK ⁵ guidelines recommend testing all diarrheal specimens as early as possible if an infectious cause is suspected rather than waiting until 3 episodes of diarrhea have occurred. This approach allows early implementation of appropriate infection prevention and control precautions as delays may increase the risk of C. difficile transmission. Likewise, the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) guidelines ⁶ (also cited by Kundrapu et al ¹ ) recommend testing for C. difficile or its toxins on diarrheal (unformed) stool only, unless ileus is suspected. The usual presentation of CDI is defined in IDSA/SHEA guidelines as ≥3 episodes of diarrhea within 24 hours; however, they do not specify that stool specimens are not to be tested unless the patient has at least 3 unformed stools.

Assuming that stool specimens meet the necessary requirements for laboratory testing (ie, unformed), we are not convinced that the laboratory is the appropriate place to decide whether specimens be tested for C. difficile. Notably, of the patients defined as ‘not meeting clinical criteria for testing,’ a significant proportion (37%) had received antibiotics within the previous 90 days, ¹ which is a risk factor for CDI and should have prompted testing. As with many infections, CDI should be diagnosed on clinical grounds with laboratory results supporting the diagnosis, and not vice versa. ⁷ We are concerned that implementation of the authors’ proposal to reduce testing in patients not meeting clinical criteria for CDI may have a detrimental effect on efforts to control the dissemination of C. difficile spores in the hospital environment. While the use of the clinical definition is useful to provide a standardized definition for reporting, this definition is more suitable for standardized surveillance purposes than for laboratory processing. A significant limitation of this study, as acknowledged by the authors, is the absence of C. difficile toxin testing. Had the diagnostic testing included an assay for C. difficile, it would have added certainty to the decision to exclude these patients as CDI cases and more validity to their strict use of this case definition. ^{8 , 9}

We agree that details of the patient’s clinical presentation are needed for accurate interpretation of CDI laboratory results; however, we suggest that this be done after the laboratory has tested the (unformed) stool specimen. Because C. difficile laboratory results are used not only to manage patients with CDI but also to minimize C. difficile transmission risk, we argue that delaying specimen acquisition until the patient has had ≥3 episodes of diarrhea in 24 hours increases the risk of C. difficile transmission. If strategies are required to reduce inappropriate laboratory testing, clinician engagement and education are key to ensuring correct patient selection based on clinical assessment. We suggest that stool specimens be sent to the laboratory when CDI is clinically suspected, regardless of the number of episodes of diarrhea, and we suggest that clinical correlation be required between the patient’s symptoms and laboratory results. As well as improving laboratory efficiency, this approach minimizes cross infection by promoting early implementation of infection prevention and control precautions; it also prevents inappropriate treatment of asymptomatic carriers.