Pseudomembranous Colitis


Overview

Etiology

  • Broad-spectrum antibiotics disrupt the normal bowel flora, the most common causative agents being ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones.
  • Clostridium difficile colonization occurs after this disruption to bowel flora by ingestion of heat-resistant spores, which convert to vegetative forms in the colon.
  • C difficile produces 2 exotoxins that are responsible for the resulting adverse effects.

Pathophysiology

  • Clostridium difficile are gram-positive, anaerobic, spore-forming rods that produce toxins A and B. These toxins cause an inflammatory response in the large intestine, leading to increased vascular permeability and pseudomembrane formation. Colonic pseudomembranes have a distinct appearance of adherent raised yellow and white plaques against an inflamed mucosa, and are composed of neutrophils, fibrin, mucin, and cellular debris.
  • Toxin A is thought to play a more critical role than toxin B in the pathogenesis as it has been found to induce greater tissue damage and fluid accumulation in experimental animal models. Toxin B is thought to play a role only after the colonic mucosa has already been damaged by toxin A.
  • Depending on host immune responses and whether or not the strain of C difficile is toxigenic, either an asymptomatic carrier state develops or a C difficile-associated disease (CDAD). Asymptomatic carriers are less likely to have evidence of toxin formation.
  • Clinical manifestations usually occur on days 4 through 9 of antibiotic therapy but may occur up to 8 weeks after discontinuation of antibiotics.
  • Debilitated patients may be unable to mount an immunogammaglobulin immune response to toxin A
     

Clinical Presentation

  • Diarrhea
  • Abdominal pain
  • Fever
  • Nausea and vomiting
  • Abdominal distension
  • Abdominal tenderness
  • Symptoms of shock

Diagnostic Testing

1st Tests To Order
  • CBC
  • Stool guaiac (fecal occult blood test)
  • Stool immunoassay for toxins A and B
  • Stool PCR
  • Abdominal x-ray

Other Tests to Consider

  • stool cytotoxin tissue culture
  • abdominal CT scan
  • sigmoidoscopy or colonoscopy
     

Risk Factors

Strong
  • Antibiotic exposure
    • The most common antibiotics involved are ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones, especially in the preceding 3 months.
  • Advanced age
    • Patients of advanced age are at increased risk.
  • Hospitalization or residence in a nursing home
    • Pseudomembranous colitis is the most important cause of nosocomial diarrhea in adults.
  • History of Clostridium difficile-associated disease
    • Approximately 5% to 20% of treated patients will have a recurrence after discontinuation of therapy. A small number of patients have repeated relapses, necessitating several courses of treatment or trials of tapering or pulsed-dose vancomycin.
Weak
  • Severe underlying illness
    • Illness for which antibiotics were prescribed or severe underlying illness.
  • Immunosuppressive agents or chemotherapy
    • Association between use of immunosuppressants and development of condition.
  • Proton-pump inhibitors
    • Association between use of proton-pump inhibitors and development of condition. 
  • Gastrointestinal surgery
    • Association between gastrointestinal surgery and development of condition.
  • Inflammatory bowel disease
    • Association between inflammatory bowel disease and development of condition

 

Differential Diagnosis

Disease/Condition Differentiating Signs/Symptoms Differentiating Tests
Antibiotic-associated diarrhea (AAD) AAD includes osmotic diarrhea associated with antibiotic use.
Nausea and diarrhea present.
Absence of fever.
All tests within normal limits.
Negative tests for Clostridium difficile toxin.
Ischemic colitis History of stroke, hypotension, heart failure, diabetes, or abdominal radiation exposure.
Symptoms of bloody diarrhea, abdominal pain, vomiting, and fever.
Colonoscopy reveals inflamed mucosal surface or ischemic ulcers.
Angiography reveals arterial flow disruption.
Bacterial or viral gastroenteritis History of travel, eating contaminated food, or family members also ill.
Stool and blood bacterial culture tests warranted.
May have history of bloody stools.
Blood as well as stool culture positive for invasive bacterial infection.
Inflammatory bowel disease Chronic diarrhea that may be bloody with extraintestinal manifestation. Colonoscopic and pathologic findings suggestive of inflammatory bowel disease.
 

Treatment

Acute
Patient Group Tx Line Treatment
nonpregnant:
mild to moderate disease
1st metronidazole: 250-500 mg orally/intravenously every 6-8 hours for 10-14 days
  • Oral metronidazole is the most cost-effective initial therapy and should be used first line in mild to moderate disease unless there is a contraindication to its use or the patient is pregnant.
  • IV is given to hospitalized patients unable to take oral medications.
plus discontinuation of causative agent
  • At the first suggestion of diagnosis, all antibiotics should be discontinued if possible. If antibiotics cannot be withdrawn, an agent less likely to cause pseudomembranous colitis should be substituted. In particular, ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones should be avoided.
plus supportive care and infection control measures
  • Fluid and electrolyte status should be evaluated and maintained. Infection control measures should be instituted. Patients who are hospitalized should be placed in a private room. Other infection control measures should include use of barrier precautions, hand hygiene with soap and water, and avoidance of rectal thermometers.
2nd oral vancomycin or fidaxomicin (for failure to respond within 7 days to metronidazole)
  • Vancomycin can be administered via nasogastric tube or retention enema in patients who cannot tolerate oral medications. Vancomycin is not effective for this condition when given IV.
  • Data suggest that fidaxomicin is effective for the treatment of mild to moderate Clostridium difficile infection. It is now approved as first-line therapy for C difficile. Fidaxomicin has been shown to be superior to vancomycin in sustained clinical response and reducing recurrence.

Primary Options

  • Vancomycin : 125-500 mg orally four times daily for 10-14 days
  • Fidaxomicin : 200 mg orally twice daily for 10 days
nonpregnant:
Severe disease
1st oral vancomycin
  • Vancomycin is preferred in patients who have severe disease at presentation.
  • Severe disease is characterized by 2 or more factors:
    •  Age > 60
    • Temp > 38.3C (100.9 F)
    • Albumin < 2.5,
    • WBC > 15,000,
    • Creatinine increase 50%)
      OR
    • WBC > 15,000 and creatinine 1.5xbaseline (no agreement on standard definition of severe disease)
    • WBC 20,000 to 30,000/mm^3 but  No systemic symptoms of shock.
  • Vancomycin can be administered via nasogastric tube in patients who cannot tolerate oral medications.
  • Vancomycin is not effective for this condition when given IV.

Primary Options

  • Vancomycin : 125-500 mg orally four times daily for 10-14 days
plus discontinuation of causative agent
  • At the first suggestion of diagnosis, all antibiotics should be discontinued if possible. If antibiotics cannot be withdrawn, an agent less likely to cause pseudomembranous colitis should be substituted.
  • In particular, ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones should be avoided.
plus supportive care and infection control measures
  • Fluid and electrolyte status should be evaluated and maintained. Infection control measures should be instituted. Patients who are hospitalized should be placed in a private room. Other infection control measures should include use of barrier precautions, hand hygiene with soap and water, and avoidance of rectal thermometers.
nonpregnant:
Fulminant disease
1st metronidazole plus oral vancomycin
  • Vancomycin can be administered by retention enema or nasogastric tube, and metronidazole can be administered IV if necessary.
  • Vancomycin is not effective for this condition given IV.

Primary Options

  • Vancomycin : 250-500 mg orally four times daily for 10-14 days
    -- and--
  • Metronidazole : 250-500 mg orally/intravenously every 6-8 hours for 10-14 days
plus discontinuation of causative agent
  • At the first suggestion of diagnosis, all antibiotics should be discontinued if possible. If antibiotics cannot be withdrawn, an agent less likely to cause pseudomembranous colitis should be substituted.
  • In particular, ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones should be avoided.
plus supportive care and infection control measures
  • Fluid and electrolyte status should be evaluated and maintained. Infection control measures should be instituted. Patients who are hospitalized should be placed in a private room. Other infection control measures should include use of barrier precautions, hand hygiene with soap and water, and avoidance of rectal thermometers.
adjunct Surgery
  • Fulminant disease is underappreciated as a life-threatening disease because of a lack of awareness of its severity and its nonspecific clinical syndrome.
  • Early diagnosis and treatment are essential for a good outcome, and early surgical intervention should be used in patients who are unresponsive to medical therapy.
  • The surgical procedure of choice is a total abdominal colectomy with end ileostomy, although the mortality rate remains high.
pregnant 1st Oral vancomycin: 125-500 mg orally four times daily for 10 days
  • Vancomycin is first-line therapy in pregnant patients.
  • It can be administered via NG tube or retention enema in patients who cannot tolerate oral medications.
  • Retreatment may be necessary when patients fail to respond to treatment.
plus discontinuation of causative agent
  • At the first suggestion of diagnosis, all antibiotics should be discontinued if possible. If antibiotics cannot be withdrawn, an agent less likely to cause pseudomembranous colitis should be substituted.
  • In particular, ampicillin, second- and third-generation cephalosporins, clindamycin, and fluoroquinolones should be avoided.
plus supportive care and infection control measures
  • Fluid and electrolyte status should be evaluated and maintained.
  • Infection control measures should be instituted.
  • Patients who are hospitalized should be placed in a private room.
  • Other infection control measures should include use of barrier precautions, hand hygiene with soap and water, and avoidance of rectal thermometers.
adjunct Surgery for fulminant disease
  • Fulminant disease is underappreciated as a life-threatening disease because of a lack of awareness of its severity and its nonspecific clinical syndrome.
  • Early diagnosis and treatment are essential for a good outcome, and early surgical intervention should be used in patients who are unresponsive to medical therapy.
  • The surgical procedure of choice is a total abdominal colectomy with end ileostomy, although the mortality rate remains high.

Admit Orders: C. Diff Colitis

1. Admit to:

2. Diagnosis: C. Diff Colitis

3. Condition:

4. Vital Signs: q6h; call physician if BP >160/90, <80/60; P >120; R>25; T >38.5°C.

5. Activity: Up ad lib.

6. Nursing: Daily weights, inputs and outputs, +/- NGTube

7. Diet: NPO. Advance to clear liquids as tolerated.

8. IV Fluids: 0.5-2 L NS over 1-2 hr then, D5 ½ NS at 125 cc/hr. NG tube at low intermittent suction (if obstructed).

9. Special Medications:

Inpatient Regimen:

     -Metronidazole: 250-500 mg orally/intravenously every 6-8 hours for 10-14 days

  -OR-

-Vancomycin : 125-500 mg orally four times daily for 10-14 days
  -OR-
-Fidaxomicin : 200 mg orally twice daily for 10 days

 

Fulminant disease:
   - Vancomycin : 250-500 mg orally four times daily for 10-14 days
       -- and--
   -  Metronidazole : 250-500 mg orally/intravenously every 6-8 hours for 10-14 days

 10. Symptomatic Medications: - Morphine sulfate 5-10 mg IV push prn pain.
 - Zolpidem (Ambien) 5-10 mg qhs PO prn insomnia.
 - Zofran 4mg IV q4-6h prn
 -Acetaminophen (Tylenol) 650 mg 2 tab PO/PR q4-6h prn temp >38°C or pain.
 -Docusate sodium (Colace) 100 mg PO qhs.
 -Famotidine (Pepcid) 20 mg IV/PO q12h.
 -Heparin 5000 U SQ q12h or pneumatic compression stockings
 

11. Extras: Acute abdomen series, CXR PA and LAT, ECG, CT of abdomen w/ PO & IV Contrast, ultrasound, surgery and GI consults.

12. Labs: CBC with differential, CMP, amylase, lipase, blood cultures x 2, drug levels peak and trough 3rd dose. UA, urine C&S. Stool WBC, culture for enteric pathogens, ova and parasites x 3, clostridium difficile toxin.

 
ITE 2013, Q#230.
A 70-year-old female with a past history of hypertension and diabetes mellitus is hospitalized with pneumonia and treated with antibiotics. She subsequently develops two Clostridium difficile infections and is appropriately treated with antibiotics each time. Ten weeks after her initial hospitalization she has her third episode of C. difficile infection.
Which one of the following would be the most appropriate treatment?

A) A 14-day course of linezolid (Zyvox)
B) A 14-day course of oral vancomycin (Vancocin) and metronidazole (Flagyl)
C) A 14-day course of intravenous vancomycin
D) A 4-week course of clindamycin (Cleocin)
E) A 15-week oral vancomycin taper

ANSWER: E

  • Clostridium difficile infections are associated with a high rate of recurrence. Approximately 20% of patients successfully treated for C. difficile will have a relapse.
  • For the first relapse, a 10- to 14-day course of oral metronidazole is recommended if symptoms are moderate.
  • If symptoms are severe, a 10- to 14-day course of oral vancomycin is indicated.
  • If a second relapse is confirmed, an oral vancomycin taper over approximately 15 weeks is recommended.
    • The regimen is 125 mg every 6 hours for 10–14 days, then 125 mg every 12 hours for 7 days, then 125 mg daily for 7 days, then 125 mg every other day for 8 days, followed by 125 mg every 3 days for 15 days.
  • Intravenous vancomycin is not effective for C. difficile infections.
  • Clindamycin is a common cause of C. difficile infection and has no role in its treatment.

    Ref: Friedman LS, Brandt LJ (eds): Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, ed 9. Saunders, 2010, p 1901.


ITE 2014 Q88.
Which one of the following strategies for preventing the spread of Clostridium difficile infection has been shown to be most effective?

A) Use of alcohol-based hand sanitizer
B) Handwashing with soap and water
C) Screening health care providers for the carrier state
D) Administration of probiotics to at-risk patients
E) Use of N95 masks and negative-pressure rooms


ANSWER: B