Clostridioides Difficile Colitis

Clostridioides Difficile Colitis

1. Bacteriology
• C. difficile is a gram-positive, spore-forming, toxin-producing, anaerobic bacteria
• most commonly associated with antibiotic use and disruption of the normal microbiome
• pathogenetic strains produce two toxins (A and B) that are responsible for the symptoms of C. difficile infection (CDI)
• hypervirulent strains have emerged that produce 16X to 20X more toxin than less virulent strains
• pathogen most responsible for nosocomial infectious diarrhea


2. Infection Risk Factors
• prior treatment with antibiotics, especially fluoroquinolones, clindamycin, cephalosporins, and penicillins
• antibiotics suppress the normal colon flora, allowing overgrowth of C. difficile
• other risk factors include age > 65, current or recent hospitalization, and use of proton pump inhibitors


3. Clinical Presentation
• infection (CDI) can vary from mild diarrhea to fulminant infection with toxic megacolon and systemic sepsis
• infection typically begins within 4 to 9 days after starting antibiotics
• 25% of patients may present up to 10 weeks after a course of antibiotics


1. Mild Disease
• main symptom is watery diarrhea – more than 3 loose stools / 24 hrs
• other symptoms include lower abdominal pain and cramping, low-grade fever, anorexia, and nausea
• physical exam may demonstrate lower abdominal tenderness
• average WBC count is 15,000


2. Severe Disease
• diffuse abdominal pain and distention
• hypovolemia, elevated creatinine, and lactic acidosis are common
• WBC count may be as high as 40,000


3. Fulminant Disease
• hypotension may progress to shock and multisystem organ failure
• toxic megacolon
• bowel perforation with peritonitis
• WBC count may be > 50,000


4. Recurrent Disease
• 25% of patients relapse within 30 days of completing treatment
• recurrent disease can be mild, severe, or fulminant
• one major risk factor for recurrence is the ongoing need for concomitant antibiotics during treatment for CDI


5. Asymptomatic Carriers
• 20% of hospitalized patients are asymptomatic carriers
• no need to screen for these patients, and no need for treatment or contact precautions


4. Diagnosis
1. Stool Studies
• CDI is diagnosed by a positive test for C. difficile toxins or the C. difficile toxin B gene
• there are several diagnostic tests available, each with their advantages and disadvantages


1. GDH Antigen Test
• uses antibodies to test for the GDH enzyme, a protein present in all C. difficile species
• cheap and fast
• a negative test is useful (good sensitivity)
• a positive test, however, cannot distinguish between toxigenic and nontoxigenic strains (poor specificity)


2. Toxin A and B Test
• low cost, fast turnaround
• both toxins should be tested for
• a positive test is valuable (high specificity)
• high rate of false negatives (low sensitivity)


3. Interpretation of Results
• if both tests are positive, then the patient should be treated for CDI
• if both tests are negative, then the patient does not have CDI
• discordant results (one test positive, the other negative) should be resolved with the NAAT test


4. NAAT Test
• polymerase chain reaction test for the gene encoding toxin B
• a positive test is considered evidence of CDI, as long as one of the first two tests was also positive


2. Endoscopy
• not usually necessary unless another diagnosis is suspected that requires direct visualization and/or biopsy
• flexible sigmoidoscopy or colonoscopy may identify the plaque-like pseudomembranes which are pathognomonic for CDI
• pseudomembranes are found in 25% of patients with mild disease, and 87% with fulminant colitis







5. Management
1. Medical Management
1. Infection Control
• initiate hospital infection control practices
• contact precautions
• hand-washing with soap and water may be more effective than alcohol-based hand sanitizers since C. difficile spores are resistant to alcohol


2. Antibiotic Management
• discontinue the offending antibiotics if possible
• if continued antibiotic treatment is necessary, then switching to other agents less frequently implicated in CDI is prudent


3. Diarrhea Management
• correct fluid and electrolyte losses
• antimotility agents (loperamide and opiates) are usually avoided, but the evidence that they cause harm is not strong
• patients can have a regular diet as tolerated


4. Treatment
1. Mild Disease
• oral vancomycin is the preferred antibiotic
• oral fidaxomicin and oral metronidazole are alternatives
• treatment course is for 10 days


2. Severe or Fulminant Disease
• higher doses of antibiotics are used
• a second agent may be added if no response
• drugs may need to be given via an NG tube
• in refractory cases, vancomycin can be given as an enema, but is associated with perforation


2. Surgery
1. Indications
• toxic megacolon
• perforation
• failure of medical management with ongoing systemic toxicity


2. Procedures
1. Total Abdominal Colectomy with End ileostomy
• indicated for perforation, necrosis, or abdominal compartment syndrome
• residual infection in the rectal pouch may be managed with vancomycin flushes through a rectal tube
• since CDI is a pancolonic disease, segmental colectomy is not indicated for isolated areas of perforation or necrosis


2. Diverting Loop Ileostomy with Colonic Lavage
• since the mortality rate of abdominal colectomy and ileostomy is so high (34% to 57%), other surgical options have been explored
• one promising procedure is laparoscopic loop ileostomy creation with intraoperative antegrade colonic lavage using polyethylene glycol
• the fluid is collected with a rectal tube
• postoperatively, vancomycin irrigation through the ileostomy is continued for 10 days
• associated with lower mortality and higher ileostomy reversal rates in nonrandomized studies than total abdominal colectomy