Pseudomembranous Colitis

Pseudomembranous colitis is a bacterial disease of the colon caused by Clostridium difficile. Pseudomembranous colitis is characterized by mucosal inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections account for the most commonly diagnosed hospital-acquired diarrheal illnesses. C. difficile infections can range from asymptomatic colonization to diarrhea and progress to fulminant colitis with systemic sepsis in severe cases. The diagnosis is established based on stool studies. Management of pseudomembranous colitis is mainly using antibiotics. Fecal transplant is considered in a few cases, whereas surgical intervention is required in severe cases.

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Overview

Definition

Pseudomembranous colitis is an inflammation of colonic mucosa caused by the toxins released by Clostridium (now reclassified as Clostridioides) difficile.

Epidemiology

  • Accounts for up to 3 million cases of diarrhea and colitis in the United States every year
  • Approximately 14,000 deaths in the US every year
  • The majority of cases are hospital acquired.
  • Up to 40% of cases of C. difficile colitis are community acquired.

Etiology

  • Caused by toxigenic strains of C. difficile: 
    • Gram-positive bacillus, obligate anaerobe
    • C. difficile can exist in 2 forms:
      • Spore form: outside the colon; resistant to heat, acid, and antibiotics
      • Vegetative form: in the intestine
    • Highly contagious
    • Spores transmitted via fecal-oral route
  • Recent antibiotic treatment is the main risk factor. Most commonly implicated antibiotics:
    • Clindamycin 
    • Cephalosporins
    • Fluoroquinolones
    • Ampicillin
  • Other risk factors:
    • Proton-pump inhibitors (gastric-acid suppression)
    • Advanced age > 65
    • Medical comorbidities
    • Hospitalization
    • Gastrointestinal surgery
    • Enteral feeding
    • Obesity
    • Chemotherapy
    • Hematopoietic stem cell transplantation
    • Inflammatory bowel disease
    • Cirrhosis

Pathophysiology and Clinical Presentation

Pathogenesis

  • 2%–3% of healthy adults are colonized with C. difficile.
  • 8%–10% of hospitalized adults are colonized.
  • Disruption of the normal flora using antibiotics leads to the overgrowth of C. difficile.
  • Most of the clinical infections are observed in newly colonized patients.
  • Intestinal damage is due to toxin release.
  • Toxins released by C. difficile:
    • Enterotoxin A:
      • Targets brush-border enzymes
      • Alters fluid secretion
      • Causes watery diarrhea
    • Toxin B (10 times more potent):
      • Depolymerizes actin 
      • Disrupts cytoskeleton of enterocytes
      • Causes pseudomembranous colitis

Clinical presentation

  • Foul-smelling non-bloody diarrhea
  • Cramping abdominal pain
  • Fever, nausea, and vomiting
  • Dehydration
  • Leukocytosis
  • Fulminant colitis: 
    • Acute abdominal distention and pain
    • Signs of sepsis:
      • Hypotension
      • Tachycardia
      • Change in mental status
    • Diarrhea may be absent at this point because of the developing colonic ileus.
    • Toxic megacolon
      • Large bowel dilatation > 7 cm; cecum > 12 cm
      • Systemic toxicity
    • Colonic perforation, ischemia, and necrosis can develop.
Table: C. difficile infection (CDI) classification based on severity
CharacteristicsMild-to-moderate colitisSevere colitisFulminant colitis
Number of loose stools/day< 6≥ 6≥ 6
Fever+/–+/–
WBC count< 20,000/µL> 20,000/µL> 20,000/µL
Severe abdominal pain++
Rising creatinine levels+/–+/–
Multiorgan dysfunction+
Complete ileus or toxic megacolon+
Radiological signs of colitis, ileus, or toxic megacolon+/–+
Adapted from: Courtney Cassella. (2016). Imaging in Clostridium difficile infection. Retrieved February 8, 2021, from https://sinaiem.org/imaging-in-clostridium-difficile-infection/

Diagnosis

History

  • Acute onset of diarrhea without alternative explanations
  • Treatment using antibiotics in the past 3 months
  • Hospitalization
  • Recent abdominal surgery
  • Chronic medical conditions

Physical exam

  • Findings minimal in mild cases
  • Severe colitis:
    • Diffuse abdominal tenderness/distention
    • Signs of dehydration/sepsis: tachycardia, hypotension, fever, low urine output

Laboratory studies

  • Stool studies:
    • Polymerase chain reaction (PCR) for C. difficile genes 
    • Enzyme immunoassay (EIA) for C. difficile antigen (rapid, widely available)
    • EIA for C. difficile toxins A and B
  • Blood tests:
    • Leukocytosis (often > 20,000/μL)
    • Hypokalemia (due to diarrhea)
    • Findings in fulminant colitis:
      • Serum creatinine > 1.5 (possible kidney injury caused by dehydration)
      • ↑ Lactate levels 
      • Serum albumin < 2.5 g/dL

Imaging

  • Abdominal X-ray: 
    • Can show colonic dilatation 
    • Free air in case of perforation
  • Computed tomography (CT) scan:
    • Can detect colitis, ileus, or toxic megacolon
    • Can reveal complications such as perforation
    • Findings of pseudomembranous colitis:
      • “Accordion sign” (with orally administered contrast; mucosal edema and inflammation)
      • “Target sign,” “double-halo sign”: signs of mucosal edema
      • Thickening of the colonic wall
      • Pericolonic stranding
      • Ascites
CT scan of pseudomembranous colitis

Computed tomography scan of severe pseudomembranous colitis: diffuse colonic wall thickening, with areas suggestive of mucosal hemorrhage

Image: “Abdominal computer tomography” by Division of Gastroenterology and Hepatology, Department of Medicine and Geriatrics, Tuen Mun Hospital, Tsing Chung Koon Road, Tuen Mun, New Territories, Hong Kong. License: CC BY 4.0

Flexible sigmoidoscopy

  • Not necessary if diagnosis is confirmed based on stool studies
  • Only needed if alternative diagnosis is considered
  • Full colonoscopy is not recommended because of the risk of perforation.
  • Findings:
    • Erythema
    • Friable mucosa
    • Bowel-wall edema
    • Pseudomembranes:
      • Raised yellow or off-white plaques up to 2 cm in diameter
      • Form as a result of mucosal ulceration

Management

Management of CDI

Algorithm for an approach to the management of Clostridium difficile infections (CDIs). Cr: creatinine, IV: intravenous

Image by Lecturio.

Medical management

  • Intravenous resuscitation, electrolyte correction
  • Stop the offending antibiotic if possible.
  • Oral vancomycin
  • Rectal vancomycin for patients with pronounced ileus
  • Oral fidaxomicin
  • Oral or intravenous metronidazole
  • Fecal transplant:
    • As an alternative to surgery in the case of fulminant colitis
    • For recurrent CDI 
    • For patients who have not responded to at least 2 appropriate antibiotic regimens

Surgery

Possible indications:

  • Hypotension
  • Fever > 38.5ºC (101.3ºF)
  • Significant abdominal distension
  • Peritonitis
  • Altered mental status
  • Serum lactate > 2.2 mmol/L
  • Leukocytosis > 20,000 cells/mL
  • Admission to the intensive care unit
  • Failure to improve with medical therapy
  • Colon perforation

Surgical interventions:

  • Total abdominal colectomy with end ileostomy 
  • Segmental colectomy is usually not recommended.
  • Alternative to colectomy: 
    • Diverting-loop ileostomy with colonic lavage
    • Not an option if perforation or necrosis is present

Prevention of hospital transmission

  • Gloving of personnel
  • Isolation of the patient with designated bathroom facilities
  • Avoiding the use of contaminated electronic thermometers and stethoscopes
  • Use of hypochlorite (bleach) solution to decontaminate the rooms of patients
  • Hand washing with soap (alcohol-containing hand gels are not sporicidal
  • Restricting the use of specific antibiotics:
    • Clindamycin
    • 2nd- and 3rd-generation cephalosporins

Prognosis

  • Up to 25% of patients will experience recurrence within 30 days of completing treatment.
  • Patients experiencing recurrence are at a higher risk of further recurrence.
  • The overall mortality from pseudomembranous colitis is 4.9%–6.2%.

Differential Diagnosis

  • Crohn’s disease (CD): a chronic, recurrent condition that causes patchy transmural inflammation in the terminal ileum and proximal colon. Patients with CD typically present with intermittent non-bloody diarrhea and crampy abdominal pain. Management is with corticosteroids, azathioprine, antibiotics, and anti-tumor necrosis factor (TNF) agents. Complications include malabsorption, intestinal obstruction or fistula, and an increased risk of colon cancer. 
  • Ulcerative colitis (UC): an idiopathic inflammatory condition that involves the mucosal surface of the colon. Diffuse friability, erosions with bleeding, and loss of haustra are observed in UC. Patients present with bloody diarrhea, colicky abdominal pain, tenesmus, and fecal urgency. Diagnosis is established based on endoscopy with biopsy. Management is with topical mesalamine or 6-mercaptopurine, or colectomy for severe cases.
  • Infectious diarrhea (Staphylococcus aureus, Klebsiella oxytoca, Clostridium perfringens, and Salmonella): presents with clinical manifestations similar to those of C. difficile infections. The diagnosis is distinguished based on stool culture. Management is mostly supportive and requires the use of antibiotics in some cases.
  • Diarrheagenic Escherichia coli: causes enteritis, enterocolitis, and colitis. Patients usually present with watery/bloody diarrhea, vomiting, and fever. Diagnosis is established based on culture and/or PCR using stool samples. The treatment consists of supportive therapy (fluids and electrolytes). Although antibiotics are reserved for severe/persistent cases, they are contraindicated in a few cases.

References

  1. Aberra F.N. (2019). Clostridioides (Clostridium) difficile colitis. Retrieved 29 January 2021, from https://emedicine.medscape.com/article/186458-overview#a6 
  2. Ananthakrishnan A.N. Clostridium difficile infection: Epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol. 2011 Jan. 8(1):17-26.
  3. Cohen S.H., Gerding D.N., Johnson S., et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May. 31(5):431-55. 
  4. Kelly C.P., Lamont J.T., Bakken J.S. (2021). Clostridioides (formerly Clostridium) difficile infection in adults: Treatment and prevention. Retrieved 29 January 2021, from https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-infection-in-adults-treatment-and-prevention
  5. Lamont J.T., Kelly C.P., Bakken J.S. (2020). Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis. Retrieved 21 January 2021, from https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-infection-in-adults-clinical-manifestations-and-diagnosis
  6. McDonald L.C., Coignard B., Dubberke E., Song X., Horan T., Kutty P.K. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol. 2007 Feb. 28(2):140-5.
  7. Pant C., Sferra T.J., Deshpande A., Minocha A. Clinical approach to severe Clostridium difficile infection: Update for the hospital practitioner. Eur J Intern Med. 2011;22(6):561-8.

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