Key Points
- C. difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen.
- C. difficile infection (CDI) is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for toxins or detection of toxigenic C. difficile or colonoscopic or histopathologic findings revealing pseudomembranous colitis.
- Recent estimates suggest the U.S. burden of CDI is close to 500,000 infections annually although the exact magnitude of burden is highly dependent upon the type of diagnostic tests used.
- Diagnosis of CDI recommendations are dependent upon institutional policy on which patients to test. See Diagnosis section.
- Treatment recommendations no longer include metronidazole as first-line treatment for CDI of any severity. See Treatment section.
Epidemiology
Adult
- To increase comparability between clinical settings, use available standardized case definitions for surveillance of healthcare facility-onset (HO) CDI; community-onset healthcare facility-associated (CO-HCFA); and community-associated (CA) CDI (GP).
- At a minimum, conduct surveillance for healthcare facility-onset C. difficile infection (HO-CDI) in all inpatient healthcare facilities to detect elevated rates or outbreaks of CDI within the facility (W-L).
- Express the rate of HO-CDI as the number of cases per 10,000 patient-days. Express the CO-HCFA prevalence rate as the number of cases per 1,000 patient admissions (GP).
- Stratify data by patient location in order to target control measures when CDI incidence is above national and/or facility reduction goals or if an outbreak is noted (W-L).
Pediatric
- Use the same standardized case definitions (HO, CO-HCFA, CA) and rate expression (cases per 10,000 patient-days for HO, cases per 1,000 patient admissions for CO-HCFA) in pediatric patients as for adults (GP).
- Conduct surveillance for HO-CDI for inpatient pediatric facilities but do not include cases <2 years of age (W-L).
- Consider surveillance for CA-CDI to detect trends in the community (W-L).
Diagnosis
Adult
- Patients with unexplained and new onset ≥3 unformed stools in 24 h are the preferred target population for testing for CDI (W-VL).
- Use a stool toxin test as part of a multiple step algorithm (i.e., glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no pre-agreed institutional criteria for patient stool submission (see Figure 1) (W-L).
- Use a NAAT alone or multiple step algorithm for testing (i.e., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are pre-agreed institutional criteria for patient stool submission (see Figure 1) (W-L).
- Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies (S-M).
- There are insufficient data to recommend use of biologic markers as an adjunct to diagnosis (NR).
Pediatric
- Because of the high prevalence of asymptomatic carriage of toxigenic C. difficile in infants, testing for CDI should never be routinely recommended for neonates or infants ≤12 months of age with diarrhea (S-M).
- C. difficile testing should not be routinely performed in children with diarrhea who are 1–2 years of age unless other infectious or non-infectious causes have been excluded (W-L).
- In children 2 years and older, C. difficile testing is recommended for patients with prolonged or worsening diarrhea and risk factors (such as underlying inflammatory bowel disease or immunocompromising conditions) or relevant exposures (such as contact with the healthcare system or recent antibiotics) (W-M).
Figure 1. CDI Laboratory Test Recommendations Based on Pre-Agreed Institutional Criteria for Patient Stool Submission
Table 1. Summary of Available Tests for CDI in Decreasing Order of Sensitivity
| Test | Sensitivity | Specificity | Substance Detected |
|---|---|---|---|
| Toxigenic culture (TC) | High | Lowa | C. difficile vegetative cells or spores |
| Nucleic acid amplification tests (NAAT) Nucleic acid amplification tests(NAAT) | High | Low/moderate | C. difficile toxin genes |
| Glutamate dehydrogenase (GDH) | High | Lowa | C. difficile common antigen |
| Cell culture cytotoxicity neutralization assay (CCNA) | High | High | Free toxins |
| Toxin A, B enzyme immunoassays | Low | Moderate | Free toxins |
a Must be combined with a toxin test.