Clostridioides difficile (C. diff)

Urgent

CDC threat level?

Antibiotic use

What is the cause of infection?

Symptoms/Presentation

*usually start to show between 5-10 days of taking antibiotics; sometimes within 1 day to 2 months
-watery diarrhea several times a day for two or more consecutive days (mild); 10-15 times a day and thus dehydration in severe cases
-abdominal cramping
-intestinal inflammation (severe cases); more severe inflammation leads to more severe cramping
-kidney failure (severe cases)
*range of symptoms form mild to fulminant disease, pseudomembranous colitis, and toxic megacolon

Microbial Characteristics

-anaerobic toxigenic bacterium
-"difficile" to culture
-found practically everywhere in the environment (soil, water, abiotic surfaces, human and animal feces)
-spore-forming (spores shed in feces and other bodily fluids and are resistant to heat and alcohol; germinate in intestine)

Gram-negative or gram-positive?

gram-positive

Risk Factors

-antibiotic use causing depletion of protective commensals
-weak or compromised immune function/response
-old age (65 and up)
-gastric acid suppression (proton pump inhibitors)

Pathogenicity/Virulence Factors

-opportunistic colonization of large intestine
-has two toxins: TcdB and TcdA (all strains produce TcdB but others can produced both toxins); TcdB is 10x more potent
-very high number of cases in the U.S. (usually nosocomial)

Epidemiology

-453K cases of CDI in 2011, 29,000 deaths
-some people can be asymptomatic carriers which increases spread of infection; shed spores and serve as a reservoir
-carriage can be in patients in healthcare facilities
-previously colonized patients are more likely to be asymptomatic
-community-acquired infection is much rarer than nosocomial CDI, but risk is not zero

Recurrent CDI

reappearance of symptoms of CDI 2-8 weeks after the end of treatment to resolve CDI; after first recurrence of CDI the likelihood it will happen again increases

Transmission

-asymptomatic carriers and CDI patients are reservoirs causing environmental contamination
-ingestion of pores (fecal-oral route)
-fomites on abiotic surfaces
-can occur between hospital roommates and from prior bed occupants to current occupants

Clinical Presentation: Non-Severe

-watery diarrhea is primary indicator, lower abdominal tenderness, patchy erythema (reddening) to severe pseudomembranous colitis

Clinical Presentation: Severe

-watery diarrhea, lower abdominal pain, abdominal distention, leukocytosis (high WBCs), fever, hypovolemia, low blood pressure, bowel perforation, peritonitis, megacolon

Diagnosis

-CDI should be suspected if a patient presents with watery diarrhea with no obvious explanation and has had prior antibiotic use
-Laboratory diagnosis with positive PCR for toxin genes or detection of toxin in stool
-Immunodetection: ELISA method
-Cell-culture cytotoxicity: sample of C. diff from patient colon is put in culture of mammalian cells to see if it will kill the cultured cells
-Endoscopy, colonoscopy, CT imaging
-Bloodwork

Treatment

-Fidaxomicin (highly specific for C. diff)
-Vancomycin (narrow-spectrum for gram positive species)
-10 day course of these antibiotics, longer for severe cases
-Fecal microbiota transplantation (FMT) in severe cases
-Surgical intervention in severe cases (don't wait too long to choose this route)
*total abdominal colectomy preferred when colonic perforation or necrosis are present; partial colectomy not recommended