The diagnosis of Clostridium difficile infection can be complex, given the variety of available laboratory tests. What tests are appropriate for Clostridium difficile infection diagnosis, and how should these be interpreted with respect to the clinical picture? Once I have confirmed a positive laboratory diagnosis, how should I attribute Clostridium difficile infection cases?
Clostridium difficile (C. difficile) is a complex bacterium that may be found in the bowel flora of individuals without any symptoms. However, when changes occur in the normal bowel flora that enable C. difficile to grow, this can lead to diarrhea and disease, or C. difficile infection (CDI). The diarrhea is caused by the production of toxins, so the appearance of symptoms depends on an increase in C. difficile load in the colon and on the production of toxins. Immunocompromised individuals, those on chemotherapy, and those on antibiotics that alter the bacterial flora of the colon can develop C. difficile overgrowth and disease (assuming the bacterium is present and is a toxin-producer).
If a stool test is positive for C. difficile, it still must be put into a clinical context. A single diarrheal stool sample may be positive for C. difficile, but if the patient’s diarrhea disappears without treatment, C. difficile is likely not the cause of illness. If the diarrhea is caused by the use of laxatives, is CDI the cause of the diarrhea, even if a stool sample is positive for C. difficile? If the diarrhea settles quickly and without therapy after discontinuation of the laxative (which should happen because a laxative is no longer required), then C. difficile is likely not the cause. Unfortunately in situations like this where multiple interventions occur (e.g. anti-CDI antibiotics are started), the default diagnosis is often CDI.
In the past, stool culture was used to identify C. difficile, but did not define whether the accompanying toxin was present. Testing then evolved to look specifically for C. difficile toxin (S). At one time, toxin assays were done on cell cultures - a very time-consuming and expensive technique. Then, immune-based assays were used, but they were not sensitive, so a single negative test did not necessarily rule out CDI. Now with molecular techniques such as polymerase chain reaction, we have very sensitive tests; if results are negative, there is usually no CDI. However, testing may also be too sensitive and identify C. difficile even when it is not the cause of the diarrhea. Still, many hospitals do not have molecular capabilities, and they use screening tests first. Public Health Laboratories act as a service laboratory for many smaller hospitals but also as a reference laboratory for outbreak investigation, using molecular techniques to confirm that different patients have been infected with a related organism.
In summary, the diagnosis of CDI must be individualized using both the clinical picture and the laboratory data. We must always remember that we treat patients and not laboratory tests.
Dr. Gary GarberDr. Gary Garber provides medical leadership to the infection prevention and control department and medical and scientific advice on infection prevention and control to Public Health Ontario. He is a professor of medicine at the University of Ottawa and an infectious diseases physician at the Ottawa Hospital.