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Updated Clostridium difficile infection (CDI) guidelines emphasize that the optimal diagnostic method for identifying CDI is “the subject of debate and depends on how carefully patients are selected for testing,” according to a statement accompanying the guidelines, which were issued by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Still, IDSA and SHEA acknowledge the solid place molecular tests have in the work-up of CDI, with more than 70% of hospitals now using such methods.
The guidelines, published in Clinical Infectious Diseases, suggest that patients who have had at least three unexplained and new-onset unformed stools within 24 hours are the best target population for CDI testing.
Triggered by excessive antibiotic use, CDI causes 500,000 illnesses and up to 30,000 deaths in the United States each year. CDI also is a top cause of hospital-acquired infections, according to IDSA. Since the last time these guidelines were issued in 2010, methods for managing CDI have improved significantly. “We can better control this epidemic by learning how to use new treatments and diagnostics,” said L. Clifford McDonald, MD, co-chair of the guidelines panel and associate director for science in the Division of Healthcare Quality Promotion for the Centers for Disease Control and Prevention.
One reason nucleic acid amplification testing (NAAT) has been implemented widely is that toxin enzyme immunoassays (EIA) are not sufficiently sensitive and may underdiagnose CDI, Dale N. Gerding, MD, a co-author of the guidelines and a research physician at the Edward Hines, Jr. VA Hospital, Hines, Illinois, told CLN Stat. In contrast, NAAT is more sensitive than EIA and is comparable to toxigenic culture in sensitivity, Gerding said.
The guidelines recommend an algorithm that assigns specific roles for both NAAT and toxin tests. When an institution doesn’t have an across-the-board agreement on criteria for submitting stool specimens for CDI testing, the guidelines recommend a testing algorithm that includes a test for toxin in stool. “In this case, if there is a discrepancy between glutamate dehydrogenase and toxin EIA test results, then it can be arbitrated by doing a NAAT test. Or, a NAAT test can be used for screening and a toxin test for confirmation as one of the acceptable algorithms,” Gerding said. However, if there is institutionwide buy-in to test only patients who haven’t been taking laxatives but who have new onset unexplained diarrhea and more than three stools in 24 hours, then either NAAT alone or an algorithm containing a toxin test should be used, according to the guidelines.
NAATs have their own shortcomings: They lack specificity and can overdiagnose patients who are colonized with C. difficile but do not have diarrhea caused by CDI. The addition of the toxin EIA is to try to improve specificity of diagnosis, Gerding explained. “The bottom line is these are weak recommendations with low quality of evidence. We need better data for how to optimally test for CDI and, hopefully, better more sensitive and rapid tests for toxin in stool,” he added.
The guideline authors also recommend against the following:
- Repeat stool testing on asymptomatic patients, unless it’s for use in an epidemiological study;
- Repeat tests during the same episode of diarrhea that takes place within a week’s time; and
- Routine testing of neonates or infants ≤12 months of age with diarrhea, due to high prevalence of asymptomatic CDI in infants.
The document supports testing for toddlers and older children under certain circumstances: The patients have risk factors such as underlying inflammatory bowel disease, exhibit prolonged or worsening diarrhea symptoms, or were recently exposed to antibiotics or the healthcare system.
Due to insufficient evidence, the guideline makes no recommendation on using biologic markers such as fecal lactoferrin as an adjunct to diagnosis.
To treat an initial episode of CDI, the guideline suggests that clinicians replace metronidazole with vancomycin and fidaxomicin, therapies that yielded higher cure rates in studies. The document also recommends fecal microbiota transplantation (FMT) in patients who don’t respond to traditional antibiotic treatment. The Food and Drug Administration has yet to approve to FMT but did issue industry guidelines on using it to treat CDI.