Clostridioides (formerly Clostridium) difficile (C. difficile or C. diff) are an anaerobic, gram positive, rod-shaped bacteria that have the capacity to form spores that are resistant to heat and most disinfectants, which makes it difficult to eliminate them from the environment and contributes to their transmission to humans. These bacteria also have a propensity to produce various toxins that play a major role in the pathogenesis of the diseases that they cause.
C. difficile infection (CDI), also called C. difficile-associated diarrhea, is one of the most common hospital-acquired infections and the most common cause of diarrhea associated with antibiotic use. CDI ranges in severity from uncomplicated diarrhea to severe colitis and life-threatening toxic megacolon.
Only toxigenic strains of C. difficile cause infection. Toxigenic strains carry a genetic element in their genomes called the pathogenic locus that encodes several genes and other genetic elements that contribute to the development of CDI. The most important genes encode the two toxins, A and B, which are primarily responsible for the intestinal pathology of the infection. Non-toxigenic strains of C. difficile can colonize the intestine, but do not cause CDI.
C. difficile is spread from person to person through feces. The bacteria can be found in the intestine of up to five percent of people. It is transmitted through contact. Prolonged hospitalization and residence in a long-term care facility increase the likelihood of both colonization as well as the generation of C. difficile infection. Broad-spectrum antibiotic usage and other conditions that alter the normal composition of intestinal flora also predispose people to the acquisition and overgrowth of C. difficile and to the development of C. difficile infection.
A vigorous infection control program is essential for hospitals to decrease the incidence of these infections. A person who is a carrier of C. difficile may not have illness; however, can still infect another person. Preventing the spread of C. difficile requires careful hygiene including washing hands with soap and water after using the restroom and taking a shower with soap and water. Keeping surfaces, objects and clothing clean is also recommended to remove spores that can cause C. difficile.
Accurate diagnosis of C. difficile is essential for physicians to properly manage patients with antibiotic-associated diarrhea and for hospitals to effectively identify and control outbreaks of CDI. C. difficile testing should only be performed on at-risk patients with diarrhea as evidenced by multiple loose stools.
There are many diagnostic methods available for laboratories to detect toxigenic C. difficile in the stool of patients suspected of having CDI. Traditionally most tests focused on the detection of C. difficile toxins A and B. Cytotoxicity in cell culture that is neutralized by antitoxin-containing antisera is considered the reference method for toxin B detection. Stool culture for C. difficile with confirmation of toxin production (toxigenic culture) is considered the gold standard for definitive identification of CDI, but it is generally impractical for clinical diagnosis due to the length of time before a result is generated. Immunoassays for the detection of toxin A and B have been a commonly used method because of the rapid turnaround time and ease-of-use. All these toxin immunoassays, however, have been associated with relatively low sensitivity. To address this issue some manufacturers have added immunoassays for the detection of glutamate dehydrogenase (GDH) to their products. GDH is present in all strains of C. difficile but is not specifically associated with toxigenic strains and, as such, lacks specificity requiring additional testing to confirm the presence of toxigenic C. difficile.
The need for improved accuracy has promoted the development of molecular assays for the detection of pathogenic C. difficile in diarrheal stool samples. These assays are based on DNA amplification techniques that detect various conserved regions of the pathogenicity locus present in all known toxigenic C. difficile strains. Molecular tests generally all have high sensitivity and specificity when compared to toxigenic culture and high percent positive and negative agreement when compared to each other. Many of the molecular tests are based on real-time polymerase chain reaction and are relatively complex and/or expensive. More recently, some FDA-cleared tests that are based on isothermal DNA amplification technologies, such as loop-mediated amplification and helicase-dependent amplification, have been developed. These tests are less complex and less expensive because they do not require a thermocycler or fluorescent reader. These new isothermal molecular tests offer laboratories that currently are using toxin immunoassays the benefit of the high level of accuracy of a molecular test without having to incur the significantly higher costs associated with complex instruments and a highly trained molecular staff.
Proper management of CDI involves supportive care including replenishment of fluid and electrolytes lost due to diarrhea. The inciting antibiotics should be discontinued unless that is not possible due to a severe infection. Patients with mild-to-moderate CDI should be treated with metronidazole 500 mg orally three times per day for 10 days. Patients with severe CDI should be treated with vancomycin 125 mg four times daily for 10 days. Fidaxomicin is an antibiotic available for use in some circumstances. Surgical consult should be obtained for all patients with complicated CDI and surgical therapy should be considered for patients who are deteriorating. Some patients develop recurrent CDI and following treatment may require alternative prophylactic therapies such as probiotics and fecal transplantation to prevent further recurrence.