Infants <1 year old have high rates of asymptomatic toxigenic strains of C difficile, and until 2008, recommendations from SHEA discouraged testing the stools of such young patients. Because of the difficulty in differentiating incidental colonization from true CDI in this patient population, the authors of a recent review suggested using more than one diagnostic approach when testing children <1 year of age.14
We advocate a 2-step assay—that is, testing for both glutamate dehydrogenase (GDH)—an antigen common to all strains of C difficile—and C difficile toxins A and B. The common antigen test is sensitive, but may detect carriers who do not have active disease. The enzyme immunoassay (EIA) for toxins A and B helps to improve specificity. Therefore, positive results of both tests would be considered a positive finding, negative results of both tests would be considered a negative finding, and one positive result with one negative result would require another test for toxin detection.3
The reverse-transcriptase polymerase chain reaction (RT-PCR) assay, which detects the toxin B gene of C difficile, is the newest test for CDI. The RT-PCR assay detects only toxigenic strains of C difficile, and all toxigenic strains produce toxin B, making it more specific than testing for the common antigen. The RT-PCR assay also has better sensitivity than the cytotoxin assay, which also tests for toxin B. The major limitation of the RT-PCR assay is the frequency of false-positive results in hospitalized patients with a high incidence of C difficile colonization.3
Routine laboratory studies, including a complete blood count with differential and a complete metabolic panel, are often useful to ascertain the presence and degree of leukocytosis, dehydration, and other metabolic abnormalities and to test for hypoalbuminemia. Fecal leukocytes can be seen in colitis and may be useful in select cases.
Imaging studies such as radiography, CT, and endoscopy have largely been superseded by lab testing for CDI. Plain radiographs are usually normal in patients with CDI, unless the patient has an ileus or toxic megacolon. CT is useful, however, in suspected cases of fulminant CDI or toxic megacolon, and may reveal colonic-wall thickening, pericolonic stranding, or ascites.9 Colonoscopy is preferred over sigmoidoscopy because up to one-third of patients with pseudomembranous colitis will have involvement of the right colon only.9 However, this test carries the risk of perforation in patients with fulminant colitis.
TABLE 1
Lab tests for C difficile infection
| Test | Substance detected | Time needed | Sensitivity | Specificity |
|---|---|---|---|---|
| Cytotoxin | Toxin B | 1-3 d | 95% | 90%-95% |
| Toxin culture | Toxigenic C difficile† | 3-5 d | >95% | 80%-90% |
| EIA toxin A or A/B | Toxin A or A/B | Hours | 75%-80% | 97%-98% |
| EIA GDH* | C difficile | Hours | 95%-100% | 70%-80% |
| EIA GDH* and toxin A/B | C difficile and C difficile toxin | Hours | 95%-100% | 97%-98% |
| RT-PCR | Toxigenic C difficile† | Hours | >98% | 80%-99% |
| *GDH is the common C difficile antigen. †All toxigenic strains produce toxin B. EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; RT-PCR, reverse-transcriptase polymerase chain reaction. Adapted from: Bartlett JG. Infect Control Hosp Epidemiol. 2010.3 | ||||
Treatment: What to consider, what to avoid
Of the 2 antibiotics most commonly used to treat CDI—metronidazole and vancomycin—only the latter has been approved by the US Food and Drug Administration for this indication. Nevertheless, metronidazole is generally recommended as first-line therapy and has the advantage of being much less expensive than vancomycin. However, an RCT found that oral vancomycin was superior to metronidazole in patients with severe disease.15 The time to resolution of diarrhea may be shorter with oral vancomycin than with metronidazole, as well.16
Recent guidelines suggest that clinicians consider 3 factors in deciding how to treat a first episode of CDI: the patient’s age, peak white blood cell count, and peak serum creatinine level.2 TABLE 2 presents an overview of treatment recommendations for both an initial episode of CDI and recurrences.
Treat severe CDI without delay. For patients with suspected severe CDI, treatment should be started empirically, without waiting for test results. Avoid antiperistaltic agents, which can obscure symptoms and precipitate toxic megacolon.2 Discontinue an antibiotic, if the patient is taking one, as soon as possible after the original infection has been adequately treated. If other infections need to be treated concurrently, we recommend that the course of treatment for CDI be extended until after the other antibiotic regimens have been stopped.
Avoid probiotics in this group. The use of probiotics, both for prevention and to help restore normal bowel flora in patients with CDI, has been advocated for many years. One RCT showed that a yogurt drink containing Lactobacillus and other bacteria reduced the risk of CDI in individuals ≥50 years of age who were taking antibiotics,17 but the guideline development panel recommended against using probiotics until larger trials have been completed.2