C Diff

difficile)
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Clostridium difficile (Greek kloster (κλωστήρ), spindle, and Latin difficile, difficult), also known as "CDF/cdf", or "C. difficile is the most serious cause of antibiotic-associated diarrhea (AAD) and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. The C.

difficile bacteria, which naturally reside in the body, become overpopulated: The overpopulation is harmful because the bacterium releases toxins that can cause bloating, constipation, and diarrhea with abdominal pain, which may become severe. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice.

difficile AAD have been reported in up to 20% of cases.


Bacteriology


Individual, drumstick-shaped C. difficile bacilli seen through scanning electron microscopy.

Clostridia are motile bacteria that are ubiquitous in nature and are especially prevalent in soil.

Under the microscope, clostridia appear as long, irregularly (often "drumstick" or "spindle") shaped cells with a bulge at their terminal ends. Under Gram staining, Clostridium difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen.

When stressed, the bacteria produce spores, which tolerate extreme conditions that the active bacteria cannot tolerate.
C. Antibiotics, especially those with a broad spectrum of activity, cause disruption of normal intestinal flora, leading to an overgrowth of C.This can lead to pseudomembranous colitis (PMC), the generalized inflammation of the colon and the development of pseudomembrane, a viscous collection of inflammatory cells, fibrin, and necrotic cells. Pathogenic C. The most well-characterized are enterotoxin (toxin A) and cytotoxin (toxin B), both of which are responsible for the diarrhea and inflammation seen in infected patients, although their relative contributions have been debated. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases.

Another toxin, binary toxin, has also been described, but its role in disease is not yet fully understood.
Antibiotic treatment of C. Once spores are ingested, they pass through the stomach unscathed because of their acid-resistance.

However, disinfectants containing bleach are effective in killing the organisms.
Initially named bacillus difficilis by Hall and O'Toole in 1935 because it was resistant to early attempts at isolation and grew very slowly in culture, it was renamed in 1970.
Role in disease


Micrograph of a colonic pseudomembrane in Clostridium difficile colitis, a type of pseudomembranous colitis. H&E stain.

With the introduction of broad-spectrum antibiotics and chemotherapeutic antineoplastic drugs in the latter half of the twentieth century, antibiotic (and chemotherapy) associated diarrhea became more common.

difficile infection in 1978, when a toxin was isolated from patients suffering from pseudomembranous colitis and Koch's postulates were met.
C. difficile infection (CDI) can range in severity from asymptomatic to severe and life-threatening, especially among the elderly.

People are most often nosocomially infected in hospitals, nursing homes, or institutions, although C. difficile acquisition is estimated to be 13% in patients with hospital stays of up to 2 weeks, and 50% in those with hospital stays longer than 4 weeks. C.One study found that fluoroquinolones were responsible for 55% of C difficile infections. The European Center for Disease Prevention and Control recommend that fluoroquinolones and the antibiotic clindamycin be avoided in clinical practice due to their high association with clostridium difficile. Frequency and severity of C. difficile colitis remains high and seems to be associated with increased death rates. Immunocompromised status and delayed diagnosis appear to result in elevated risk of death.

difficile-associated infection/disease have also been linked to the use of medication to suppress gastric acid production: H2-receptor antagonists increased the risk twofold, and proton pump inhibitors threefold, mainly in the elderly. It is presumed that increased gastric pH, (alkalinity), leads to decreased destruction of spores.
The emergence of a new, highly toxic strain of C.

The presence of any one of these findings has a sensitivity of 86% and a specificity of 45%. In this study of hospitalized patients with a prevalence of positive cytotoxin assays of 14%, the positive predictive value was 20% and the negative predictive value was 95%.
Cytotoxicity assay
C. difficile toxins have a cytopathic effect in cell culture, and neutralized with specific anti-sera is the practical gold standard for studies investigating new CDAD diagnostic techniques. Toxigenic culture, in which organisms are cultured on selective medium and tested for toxin production, remains the gold standard and is the most sensitive and specific test, although it is slow and labour-intensive.
Toxin ELISA
Assessment of the A and B toxins by enzyme-linked immunoabsorbant assay (ELISA) for toxin A or B (or both) has a sensitivity of 63–99% and a specificity of 93–100%: at a prevalence of 15%, this leads to a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 96%.
Experts recommend sending as many as three samples to rule-out disease if initial tests are negative.

difficile toxin should clear from the stool of previously infected patients if treatment is effective. Strains that express only the B toxin are now present in many hospitals, and ordering both toxins should occur. Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes.
Other stool tests
Stool leukocyte measurements and stool lactoferrin levels have also been proposed as diagnostic tests, but may have limited diagnostic accuracy.
Computed tomography
In a recent study, a patient who received a diagnosis of CDC on the basis of computed tomography (CT scan) had an 88% probability of testing positive on stool assay. Wall thickening is the key CT finding in this disease.

Patients who have antibiotic-associated diarrhea who have CT findings diagnostic of CDC merit consideration for treatment on that basis. A weakness of this study was the lack of comparison with the accepted cytotoxicity assay.
Treatment
Asymptomatic colonization with C.