Clostridioides difficile

Aka: Clostridioides difficile, Clostridium difficile, Pseudomembranous colitis, Pseudomembranous Enterocolitis

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II. Background

  1. First recognized in 1978 as a cause of Antibiotic-Associated Diarrhea in 1978
  2. Clostridium difficile was reclassified as Clostridioides difficile in 2016
    1. Initially included in genus Clostridium due to shared properties
    2. Later reclassified to be included in a completely different Bacterial family, Peptostreptococcaceae
    3. New genus was named Clostridioides to preserve similar naming (C. Diff) and reduce clinician confusion

III. Epidemiology

  1. Incidence
    1. U.S. Adults: 14 cases per 1000 persons
    2. Marked increase from the 65 per 100,000 in 1991, and 156 per 100,000 in 2003 in U.S.
    3. Most common Nosocomial Infection in the United States
  2. Mortality:
    1. Of >450,000 cases per year, nearly 30,000 died in 2011 (6% mortality)
  3. References
    1. Kelly (2008) N Engl J Med 359(18): 1932-40 [PubMed]

IV. Pathophysiology

  1. Obligate, anaerobic, Gram Positive, spore-forming, motile Bacillus
    1. Causes Secretory Diarrhea and mucosal injury with colitis
    2. Two toxins are typically produced
      1. Enterotoxin A (causes Diarrhea, accompanies Toxin B in some cases)
      2. Cytotoxin B (cytotoxic to colon cells, present in all cases)
  2. New virulent epidemic strain: NAP1/B1/027
    1. Strain responsible for the 5 fold increase in C. difficile infections from 1999 to 2007
    2. Toxin A/B levels are >16 fold higher than other strains
    3. Produces binary toxin in addition to typical toxins A and B
    4. Higher rate of associated Toxic Megacolon
    5. Highly Fluoroquinolone resistant
  3. Sequence of infection
    1. Normal colonic Bacteria disturbed (e.g. Antibiotics)
    2. Exposure to C. difficile
      1. C. difficile is acquired in health care settings in 94% of cases
        1. However presentation is delayed until after hospitalization in 75% of cases
      2. C. difficile is commensal in only 3% of patients
      3. C. difficile survives in hospital room >40 days
        1. Occupying a room of a prior patient with C. difficile more than doubles the C. difficile risk
        2. Flushing a toilet in a C difficile patient's room disperses contaminated bioaerosol throughout room
        3. Wilson (2020) Infect Control Hosp Epidem, published online
      4. Colonization occurs in 7 to 26% of acute care facilities
      5. Colonization risk increases for each day of hospitalization
        1. Occurs in 50% of those hospitalized >4 weeks
      6. Colonization is community acquired in 41% of cases
        1. More common young, female with few comorbidities and less severe infection
        2. Occurs without Antibiotic exposure frequently
        3. Khanna (2012) Am J Gastroenterol 107(1): 89-95 [PubMed]
    3. Colonization with Clostridium difficile
      1. Asymptomatic (carrier state)
        1. Up to 15% of healthy adults are colonized with C difficile
        2. Asymptomatic patients account for >50% C. difficile colonization cases
        3. As many as 63% of healthy newborns are colonized with C. difficile
          1. Most strains in infants are non-toxic, and likely due to peripartum hospitalization
      2. Symptomatic (typically symptoms start 3-7 days after exposure)
        1. Mild Diarrheal illness or
        2. Severe illness (Pseudomembranous colitis)

V. Risk Factors

  1. Highest risk patients
    1. Older patients over age 64 years old, and especially over age 70 years
      1. Risk of C. difficile infection increases 2% for each year over age 18 years old
    2. Debilitated patients
    3. Immunocompromised patients
      1. Includes Hematopoietic Stem Cell Transplant and Solid Organ Transplant
      2. Includes Corticosteroid use
    4. Cystic Fibrosis patients (high risk for fulminant infection)
    5. Obesity
    6. Female Gender
    7. Chronic Kidney Disease (esp. Serum Creatinine >2)
    8. Gastrointestinal conditions
      1. Enteral feeding
      2. Gastrointestinal surgery
      3. Small Bowel Obstruction or Adynamic Ileus
      4. Inflammatory Bowel Disease
      5. Cirrhosis
      6. Malnutrition or low Serum Albumin
  2. Acid suppression
    1. Proton Pump Inhibitors (e.g. Omeprazole)
      1. Highest risk as they raise gastric pH most significantly
    2. H2 Blockers (e.g. Ranitidine)
      1. Less risk than with Proton Pump Inhibitors
    3. Consider stopping indefinately following diagnosis of Clostridium difficile (due to higher risk of recurrence)
  3. Recent Antibiotic use within last 3 months (especially last 7-10 days)
    1. General
      1. All Antibiotics can cause C. difficile Diarrhea (even single dose perioperative Antibiotics)
      2. Broad-spectrum agents are highest risk
      3. Risk increases with combination Antibiotic regimens, frequent dosing and longer therapy duration
      4. Up to 40% of C. difficile are in patients without recent Antibiotic use
    2. Most common Antibiotic causes
      1. Clindamycin
        1. ClindamycinOdds Ratio 16
        2. More common cause again since resurgence for MRSA management
      2. Fluoroquinolones (e.g. Ciprofloxacin, Levofloxacin)
        1. FluoroquinoloneOdds Ratio 5.5
        2. Emerging as very common cause
      3. Broad-spectrum Cephalosporins
        1. Odds Ratio 5.7
      4. Ampicillin or Amoxicillin (most common cause in United States)
        1. Odds Ratio 2.7
      5. Macrolides (e.g. Erythromycin, Azithromycin)
        1. Odds Ratio 2.7
      6. Carbapenems (Ertapenem)
        1. Odds Ratio 1.5 to 5.7
    3. Less common Antibiotic causes
      1. Tetracycline Antibiotics (e.g. Doxycycline)
      2. Sulfonamides (e.g. Bactrim)
      3. Trimethroprim
    4. Rare Antibiotic causes
      1. Parenteral Aminoglycosides
      2. Metronidazole (used for treatment)
      3. Vancomycin (used for treatment)
    5. References
      1. Brown (2013) Antimicrob Agents Chemother 57(5): 2326-32 +PMID:23478961 [PubMed]

VI. Symptoms

  1. Asymptomatic carrier state is common
  2. Megacolon may be present without Diarrhea
  3. Inflammatory Diarrhea (variably present)
    1. Timing
      1. Incubates for 2-7 days after colonization
      2. Most cases occur on days 4-9 of Antibiotic course
      3. Onset <14 days after Antibiotics in 96% of cases
      4. All cases occur within 3 months of Antibiotics
      5. Olson (1994) Infect Control Hosp Epidemiol 15:371 [PubMed]
    2. Characteristics
      1. Frequent, watery Bowel Movements to profuse Diarrhea up to 20-30 stools daily
      2. Foul, characteristic odor may be present, but not shown in studies to be sensitive or specific
        1. Rao (2013) Clin Infect Dis 56(4):615-6 [PubMed]
      3. Mucus and occult blood often present
  4. Acute inflammatory symptoms (<50% of cases)
    1. Fever (>38.5 C in 15% of cases)
    2. Crampy Abdominal Pain
    3. Decreased appetite
    4. Malaise
    5. Nausea or Vomiting may be present in 2 to 30% of patients
    6. In severe cases, Pseudomembranous colitis and Toxic Megacolon occurs
    7. Melana and Hematochezia are uncommon (although occult blood in stool is more often present)
  5. Extraintestinal symptoms
    1. Asymmetric Oligoarticular large joint Arthralgia

VII. Labs: Diagnosis

  1. Indications: Screening
    1. At least 3 unformed stools in 24 hours (required)
    2. Antibiotic use in last 3 months
    3. Inflammatory Bowel Disease with acute exacerbation
  2. Contraindications to testing
    1. Formed stool (no Diarrhea)
    2. Recent Laxative use in prior 48 hours
    3. Testing for cure in asymptomatic patients (following treatment of active infection) is NOT recommended
    4. Children <12 months of age
      1. Infants are frequently and asymptomatically colonized with C. difficile
      2. Children 1-2 years old with prolonged Diarrhea, no other causes and who have risk factors may be tested
  3. Clostridium difficile testing
    1. Clostridium difficile PCR or Nucleic Acid Amplification Tests or NAAT (preferred)
      1. Best test efficacy and recommended by American College Gastroenterology
      2. Increased risk of overdiagnosis of asymptomatic carrier state (esp. in lower probability cases)
      3. Sufficient as single test in Immunocompromised patients (assume toxigenic in these cases)
    2. Glutamate dehydrogenase (GDH) Antigen
      1. Highly sensitive and rapid assay for Antigen produced by all C. difficile isolates
      2. Does not distinguish between toxigenic and nontoxigenic strains
      3. Positive tests are then reflexed to PCR or ELISA testing (see above)
    3. Clostridium difficile A and B toxin ELISA (or EIA)
      1. Used in combination with PCR to reduce risk of over-diagnosis
      2. Preferred over Clostridium difficile culture, and widely available
      3. Replaced the cell cytotoxicity neutralization assay (CCNA)
      4. Test Sensitivity: 75-95%
      5. Test Specificity: 83-98%
      6. Available within 2 hours of obtaining sample
      7. Aldeen (2000) Diagn Microbiol Infect Dis 36(4): 211-3 [PubMed]
  4. IDSA recommends multistep protocols (screening with GDH EIA or PCR/NAAT and reflexing to toxin EIA)
    1. GDH EIA and Toxin A/B EIA (with or without PCR/NAAT)
    2. NAAT/PCR reflex to Toxin A/B EIA
      1. NAAT/PCR alone is suffiicient in Immunocompromised patients (treat all positive cases)

VIII. Labs: Markers of Severe Infection

  1. Hypoalbuminemia
  2. Lactic Acidosis
  3. Serum Creatinine >1.5 mg/dl
  4. White Blood Cell Count >15,000 cells/uL
    1. Leukocytosis variably present (<50% of cases)
    2. White Blood Cell Count may be greater than 20,000, or even 40,000 cells/uL
    3. White Blood Cell Count greater than 30,000 is related to C. difficile in 25% of cases

IX. Imaging

  1. CT Abdomen
    1. Indications
      1. Severe complicated C. difficile colitis (e.g. severe Abdominal Pain, ileus, fever, Lactic Acidosis, severe Leukocytosis)
      2. Evaluate differential diagnosis
      3. Prior Small Bowel Obstruction or surgery
      4. Inflammatory Bowel Disease (e.g. Ulcerative Colitis, Crohn's Disease)
      5. Medical complications (e.g. Diabetes Mellitus)
    2. General Findings
      1. Colon wall thickening
      2. Pericolonic stranding may be present
      3. Low attenuation mural thickening with mucosal or submucosal edema
        1. Target sign or double halo sign (2-3 concentric rings of varying attenuation)
    3. Toxic Megacolon Findings
      1. Colon dilitation >7 cm diameter
      2. Small Bowel dilation
      3. Small Bowel air fluid levels
      4. Submucosal edema (thumb printing or bowel wall scalloping)
  2. Abdominal XRay Findings (not typically indicated)
    1. Dilated colon: >7 cm in greatest diameter (Toxic Megacolon)
    2. Small Bowel dilation or air-fluid levels may be present
    3. Mucosal edema or thumbprinting may also be present

X. Diagnostics

  1. Endoscopy (Flexible Sigmoidoscopy or Colonoscopy)
    1. Not recommended in most cases
    2. May be indicated if diagnosis is unclear
    3. Findings: Mucosal lesions with pseudomembranes

XI. Differential Diagnosis

  1. Antibiotic intolerance (resolves off Antibiotics)
  2. Infectious enteritis
    1. Acute Gastroenteritis
    2. Amebic Dysentery
    3. Klebsiella oxytoca
      1. Like Clostridium difficile, causes Antibiotic-Associated Diarrhea, that may be hemorrhagic
      2. Improves after stopping Antibiotics and NSAIDs
  3. Inflammatory Bowel Disease
  4. Ischemic Colitis

XII. Evaluation: Severe Infection Criteria

  1. See ATLAS Bedside Score System for Clostridium Difficile Infection
  2. Severe infection criteria risk stratify management (e.g. Vancomycin selection for treatment)
  3. High risk patients of severe, fulminant disease (with 2 or more of the following risk factors)
    1. Age over 60 years old
    2. Temperature >38.3 C (100.9 F)
    3. Albumin <2.5 g/dl
    4. Leukocytosis with White Blood Cell Count >15,000/L
    5. Serum Creatinine >50% increase over baseline or >1.5 mg/dl
    6. Pseudomembranous colitis on endoscopy
    7. Intensive Care unit management
    8. Zar (2007) Clin Infect Dis 45(3): 302-7 [PubMed]

XIII. Management: General Measures

  1. Discontinue Antibiotics
    1. Diarrhea resolves in up to 25% of cases with stopping
    2. If Antibiotic required, choose one with lower risk
  2. Indications to start C. difficile Antibiotics immediately (empiric while awaiting test results)
    1. Older patients
    2. Multiple comorbid conditions
    3. Antibiotics can not be discontinued
    4. Severe disease
      1. Persistent Diarrhea
      2. Dysentery (fever, Leukocytosis)
  3. Avoid and stop medications that could worsen condition
    1. Proton Pump Inhibitors
    2. Opioid
    3. Antidiarrheal agents
    4. Cholestyramine (Questran)
      1. Binds Vancomycin and Metronidazole in the Intestine lowering their efficacy against C. difficile
  4. Do not retest for toxin post-treatment if asymptomatic
    1. May be positive, but does not require treatment

XIV. Management: Adults

  1. Background
    1. Antibiotic course is typically 10 days (extend to 14 days if needed)
  2. Fidaxomicin (Dificid)
    1. Considered first-line, preferred over Vancomycin due to lower recurrence rates
    2. Dose: 200 mg orally twice daily for 10 days
    3. Macrolide that inhibits RNA Polymerase, and in turn Protein synthesis, leading to Bacterial cell death
    4. Advantages
      1. Narrow spectrum Antibiotic (C. difficile, Staphylococcus, Enterococcus)
        1. Does not affect Gram Negative Bacteria including normal bowel flora
      2. High efficacy (90% cure rate, similar to Vancomycin)
      3. Lower C. difficile recurrence rates than with Vancomycin
      4. Minimal systemic absorption when taken orally
        1. As with Vancomycin, oral Fidaxomicin primarily stays in the Gastrointestinal Tract
    5. Disadvantages
      1. Very expensive ($250/dose or $3000 to $4300 for a 10 day course)
  3. Vancomycin
    1. Precaution: Only effective for C. difficile if dosed orally or rectally
    2. Indications
      1. As of 2018, a first-line agent for C. difficile, replacing Metronidazole even in mild-moderate cases
      2. Drug of choice for severe C. difficile infection
        1. Still with risk of promoting Vancomycin resistance
        2. Had been very expensive ($600-800 per course)
          1. Inexpensive if pharmacist compounds the intravenous form into oral formulation
          2. As of 2021, Vancomycin capsules are $75 to 300 per course
          3. Firvanq oral Vancomycin solution is also available $125 per course
    3. Dose: 125-500 mg orally (or rectally) four times daily for 10-14 days (10 days is often sufficient)
      1. Use low dose (125 mg) in most patients
        1. Studies suggest 125 mg four times daily is as effective as higher doses
      2. Use high dose Vancomycin 500 mg four times daily with Metronidazole in severe, fulminant disease
        1. May deliver via Nasogastric Tube in severe cases
        2. Consider using via rectal retention enema in ileus
        3. High dose enteral doses may require serum Vancomycin level monitoring (esp. Kidney disease)
      3. Extended course may be used for persistent Diarrhea
        1. See Vancomycin recurrence protocol below
  4. Bezlotoxumab (Zinplava)
    1. Monoclonal Antibody against C. Difficile
    2. Consider in the prevention of recurrent infection (adjunctive to Antibiotics) if at least one risk factor for recurrence
      1. Age 65 years or older
      2. Immunocompromised state
      3. Severe C. Difficile infection
    3. Dose: 10 mg/kg IV infusion over 60 minutes
    4. Risk of worsening Congestive Heart Failure
  5. Metronidazole
    1. No longer recommended by IDSA as first line protocol for mild to moderate Clostridium difficile
      1. Replaced by Vancomycin and Fidaxomicin as first-line agents
      2. Resistance is growing and may approach 30% in some regions
        1. IDSA shifted to recommending oral Vancomycin as first-line in 2018
      3. Not recommended for c. difficile recurrence treatment
        1. If repeated after being used for prior management, neurotoxicity risk
    2. Metronidazole has historically been preferred for mild to moderate infection (WBC <15k, creat<1.5 mg/dl)
      1. Metronidazole is much lower cost (~$20/course) than oral Vancomycin (~$400/course)
      2. May still be a reasonable alternative in mild-moderate first cases in younger patients where first-line agents are unavailable
    3. Dose
      1. Typical: 500 mg orally every 6-8 hours for 10-14 days
      2. Lower dose: 250 mg orally q6 hours for 10-14 days
      3. Parenteral dose: 500 mg IV q8 hours for 10-14 days

XV. Management: Child

  1. Mild to Moderate disease: Metronidazole (Flagyl)
    1. Metronidazole 7 mg/kg (maximum 500 mg) orally three times daily for 7-10 days
  2. Severe disease: Vancomycin
    1. Vancomycin 5 mg/kg (to maximum 125 mg) every 6 hours for 7-10 days

XVI. Management: Recurrence - General

  1. Recurrence risk doubles with each episode
    1. Follows clearance of prior episode on appropriate Antibiotics
    2. Initial recurrence risk is 20-30% (typically within 2 months)
    3. After third episode, recurrence is virtually assured
  2. Recurrence risk factors
    1. Prolonged Antibiotic use
    2. Prolonged hospitalization course
    3. Diverticulosis
    4. Multiple comorbid illnesses
    5. Elderly patients
    6. Immunocompromised
  3. Management
    1. Vancomycin is preferred Antibiotic for recurrence management
    2. Metronidazole is not recommended for recurrence due to neurotoxicity risk
  4. Fidaxomicin (Dificid)
    1. Start: 200 mg orally twice daily for 10 days
    2. Next: 200 mg orally once every other day for 20 days
  5. Vancomycin taper
    1. Start 125 mg orally four times daily for 10-14 days,
    2. Then 125 mg orally twice daily for 7 days
    3. Then 125 mg orally daily for 7 days
    4. Then 125 mg orally once every 2-3 days for up to 8 weeks
  6. Vancomycin AND Rifamaxin
    1. Vancomycin 125 mg orally four times daily for 10 days and THEN
    2. Rifaxamin 400 mg orally three times daily for 20 days
  7. Bezlotoxumab (Zinplava)
    1. Monoclonal Antibody against C. Difficile
    2. Indicated in the prevention of recurrent infection (adjunctive to Antibiotics) if last infection in prior 6 months
    3. Dose: 10 mg/kg IV infusion over 60 minutes
    4. Risk of worsening Congestive Heart Failure
  8. Probiotics
    1. Precautions
      1. Avoid if Immunocompromised (risk of Septicemia)
      2. Take Probiotics 2 hours after Antibiotic dose
    2. Saccharomyces boulardii
      1. Dose 250 mg PO bid to tid for 1 month
      2. Has also been used with Vancomycin 500 mg PO qid
    3. Lactobacillus (Culturelle)
  9. Fecal Microbiota Spores
    1. Live-brpk (Vowst)
      1. Indicated for 3 or more C. difficile episodes within 12 months
      2. Purified, Firmicutes Bacterial spore suspension in oral capsule, from human donor feces
      3. Take 2-4 days following Antibiotic treatment of recurrent C. difficile
      4. Effective in C. difficile prevention, but at nearly $20,000 per full 12 capsule course
      5. Smith (109) Am Fam Physician 109(5): 472-3 [PubMed]

XVII. Management: Recurrence - Fecal Transfer (Stool Transplant, Fecal Bacteriotherapy, Intestinal Microbiota Transplant)

  1. See Intestinal Microbiota Transplant

XVIII. Management: Fulminant disease (high mortality rate)

  1. Background
    1. Complicates 1-3% of C. difficile cases
  2. Indications
    1. Intractable colitis, Toxic Megacolon, ileus or bowel perforation
    2. Severe Leukocytosis (e.g. White Blood Cell Count to 30,000)
    3. Serum Lactate >5
    4. Multi-system organ failure or other shock-like state
  3. Management
    1. Consult general surgery
      1. Total abdominal colectomy may be indicated in the most severe diseases
      2. Other surgical management options include diverting loop ileostomy with colonic lavage
    2. Consult gastroenterology
      1. Emergent endoscopic Stool Transplant may spare both surgery and the patient's life
    3. Antibiotic Protocol
      1. Metronidazole IV 500 mg every 8 hours AND
      2. Vancomycin 500 orally four times daily AND
      3. Vancomycin enema 500 mg in 100 cc NS q6 hours
        1. Delivered by foley in Rectum, 30 cc balloon
        2. Balloon inflated for 60 minutes after dose

XIX. Prognosis

  1. See ATLAS Bedside Score System for Clostridium Difficile Infection
  2. Findings of improvement (assess on day 5)
    1. Fever resolves within first 2 days
    2. Diarrhea resolves within first 4 days
  3. Recurrence rates
    1. After episode 1: Recurrence in up to 25%
    2. After episode 2: Recurrence in up to 65%

XX. Complications

  1. Toxic Megacolon
    1. Severe systemic toxicity AND Large Bowel dilation (>7 cm diameter colon or >12 cm diameter cecum)
  2. Bowel perforation
  3. Dehydration
  4. Electrolyte abnormality

XXI. Prevention

  1. Avoid Proton Pump Inhibitors (or other acid suppression such as H2 Blocker use) unless absolutely indicated
  2. Antibiotic Stewardship
    1. Antibiotic Stewardship decreases c. difficile infection rates by >50%
      1. Dancer (2013) J Antimicrob Agents 41(2): 137-42 [PubMed]
    2. Avoid broad-spectrum Antibiotic use if possible
      1. Narrow Antibiotic spectrum based on ongoing findings such as culture results
    3. Use Antibiotics only when indicated, and no longer than the necessary duration
  3. Probiotic Indications
    1. Recurrent C. difficile (see above)
    2. Concurrent use with Antibiotics (start while patients hospitalized)
      1. Dosing
        1. Start within 1-2 days of Antibiotic initiation
        2. Continue for 5 days beyond Antibiotic course
        3. Take 2 hours after each Antibiotic dose
      2. Probiotic species appear to be equally effective
        1. Saccharomyces boulardii (e.g. Florastor)
        2. Lactobacillus (e.g. Culturelle)
      3. Multiple studies demonstrate significant reduction in C. difficile infection following Antibiotic use
      4. Hempel (2012) JAMA 307(18): 1959-69 [PubMed]
      5. Hickson (2007) BMJ 335(7610): 80 [PubMed]
      6. Gao (2010) Am J Gastroenterol 105(7): 1636-41 [PubMed]
      7. Goldenberg (2017) Cochrane Database Syst Rev (12):CD006095 [PubMed]
  4. Prevent Clostridium difficile spore spread
    1. Spores are resistant to Alcohol, Antibiotics and antiseptics
      1. Chlorhexidine and soap are effective
    2. Contact Isolation of patient
      1. Use personal protective gear including Hand Hygiene, gowns and gloves
      2. Use disposable stethoscopes and Thermometers
      3. Continue contact precautions for at least 48 hours after Diarrhea has resolved
      4. C. difficile should not share a bathroom with other people in hospital or at home
      5. Bathroom and kitchen surfaces should be cleaned with bleach solutions
    3. Practice good hygiene
      1. Hand Washing with soap and water
      2. Hand sanitizers (e.g hand gels) are not effective against Clostridium difficile
      3. C. difficile survives outside colon as spores that are Antibiotic, heat and acid resistant
      4. Disinfect surfaces and equipment with sporicidal disinfectants
        1. Bleach
        2. Alkaline glutaraldehyde
        3. Ethylene oxide
        4. Disinfecting Ultraviolet light system (used in combination with surface cleaners)

XXII. References

  1. (2018) Presc Lett 25(4)
  2. Herbert (2012) EM:RAP C3 2(4): 3
  3. Long and Swaminathan in Swadron (2022) EM:Rap 23(1): 5-11
  4. Suntharam (2006) First 24 hours, Park Nicollet Lecture
  5. Cagle (2022) Am Fam Physician 105(3): 262-70 [PubMed]
  6. Hookman (2009) World J Gastroenterol 15(13): 1554-80 [PubMed]
  7. Hsu (2014) Am Fam Physician 90(6): 377-82 [PubMed]
  8. Jabbar (2003) Prim Care 30(1):63-80 [PubMed]
  9. Johnson (2021) Clin Infect Dis 73(1): e1029-44 [PubMed]
  10. Kyne (2001) Gastroenterol Clin North Am 30(3):753-77 [PubMed]
  11. Mounsey (2020) Am Fam Physician 101(3): 168-75 [PubMed]
  12. Schroeder (2005) Am Fam Physician 71(5):921-8 [PubMed]
  13. Winslow (2014) Am Fam Physician 89(6): 437-42 [PubMed]

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Related Studies

Ontology: Clostridium difficile (bacteria) (C0079134)

Definition (NCI) A species of Clostridium that is the most significant cause of pseudomembranous colitis.
Definition (NCI_NCI-GLOSS) A type of bacterium found in human and animal waste. Clostridium difficile is a common cause of diarrhea that occurs in hospitals. It can also cause diarrhea or other intestinal disorders in patients treated with antibiotics.
Definition (NCI_CDISC) Any bacterial organism that can be assigned to the species Clostridium difficile.
Definition (MSH) A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.
Definition (CSP) causes antibiotic-induced diarrhea or pseudomembranous colitis in humans; found in the colonic flora in 3% of healthy adults.
Concepts Bacterium (T007)
MSH D016360
SnomedCT 5933001
LNC LP16813-5, MTHU009308
English Clostridium difficile, Clostridium difficile (bacteria), Clostridium difficile (Hall and O'Toole 1935) Prevot 1938, clostridium difficile, clostridium difficile organism, difficile clostridium, clostridia difficile, clostridium difficilis, [Clostridium] difficile, Bacillus difficilis, CLOSTRIDIUM DIFFICILE, CLOSTRIDIUM DIFFICILIS, Clostridium difficilis, Clostridium difficile (organism)
Swedish Clostridium difficile
Czech Clostridium difficile
Finnish Clostridium difficile
Polish Clostridium difficile
Norwegian Clostridium difficile
Spanish Clostridium difficile (organismo), Clostridium difficile
French Clostridium difficile
German Clostridium difficile
Italian Clostridium difficile
Russian CLOSTRIDIUM DIFFICILE
Dutch Clostridium difficile
Portuguese Clostridium difficile
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Pseudomembranous colitis (SMQ) (C1869076)

Definition (MDRCZE) Pseudomembránová kolitida je těžký nekrotizační proces, který zachvacuje tlusté střevo a k němuž dochází kvůli komplikaci léčby antibiotiky. Občas se objevuje za nepřítomnosti vystavení účinkům antibiotik, kdy je často přítomný predispoziční stav, jako např. nedávná operace střev, urémie, střevní ischémie, chemoterapie, transplantace kostní dřeně. Zodpovědný patogen je „clostridium difficile", příslušník normální flóry, která narůstá za přítomnosti jistých antibiotik nebo za nepřítomnosti normální bakteriální flóry způsobené jinými faktory. Zkoušky na kultury a toxiny mohou vést k potvrzení C. difficile, ale pozitivní mikrobiologický test nebo testy za nepřítomnosti klinických nálezů nepodporují definitivní diagnózu pseudomembránové kolitidy. Mnohé zprávy o průjmu spojovaném s léčbou antibiotiky nemusejí vést k definitivním diagnózám nebo specifickým testům pseudomembránové kolitidy. Nekomplikovaný průjem vyvolaný antibiotiky obvykle spontánně přestane během dvou týdnů od ukončení podávání antibiotika. U přetrvávajících symptomů nebo zřetelné kolitidy může být nutná agresivní léčba pro obnovení rovnováhy bakteriální flóry v lumenu střevního traktu.
Definition (MDRHUN) A pseudomembranosus colitis egy súlyos, necrotizáló folyamat, ami a vastagbelet érinti és antibiotikus kezelés mellékhatásaként jelentkezik. Időnként előfordul antibiotikum hatása nélkül is; hajlamosság előző állapot miatt gyakran megfigyelhető, vagyis például nemrég végzett bélműtét, urémia, intestinalis ischaemia, kemoterápia, csontvelő transzplantáció. A felelős pathogen a "Clostridium difficile", a normal flóra egy tagja, ami bizonyos antibiotikum jelenlétében, vagy az egyéb tényezők miatt a normál flóra hiánya miatt túlságosan megnövekszik. A tenyészet és toxin vizsgálatok a C. difficile meghatározásához rendelkezésre állnak, azonban a klinikai eredmények hiányában nincsenek pozitív mikrobiológiai tesztek, melyek alátámasztanák a pseudomembranosus colitis végleges diagnózisát. Az antibiotikumos kezelés mellékhatásaként megjelenő hasmenés számos esetében lehet, hogy nincs határozott diagnózis vagy specifikus teszt a pseudomembranosus colitis megállapítására. Komplikációmentes antibiotikum éltal kiváltott hasmenés rendszerint spontán módon két héten belül elmúlik az antibiotikum szedésének beszüntetése után. Megmaradó tünetek, vagy tényleges colitis esetében esetleg aggresszív terápiára lehet szükség a baktérium flóra béltraktus lumenén belüli egyensúlyának visszaállításához.
Definition (MDR) Pseudomembranous colitis is a severe, necrotizing process that involves the large intestine and occurs as a complication of antibiotic therapy. It occasionally occurs in the absence of antibiotic exposure; a predisposing condition is often present, e.g., recent bowel surgery, uraemia, intestinal ischaemia, chemotherapy, bone marrow transplantation. The responsible pathogen is "Clostridium difficile", a member of the normal flora that overgrows in the presence of certain antibiotics or in the absence of normal bacterial flora due to other factors. Culture and toxin tests are available to identify C. difficile but a positive microbiology test(s) in the absence of clinical findings does not support a definitive diagnosis of pseudomembranous colitis. Many reports of diarrhoea associated with antibiotic therapy may not have definitive diagnoses or specific tests for pseudomembranous colitis. Uncomplicated antibiotic-induced diarrhoea usually subsides spontaneously within two weeks of antibiotic discontinuation. For persisting symptoms or frank colitis, aggressive therapy may be required to restore balance of the bacterial flora within the lumen of the intestinal tract.
Definition (MDRSPA) La colitis pseudomembranosa es un proceso grave y necrosante que afecta el intestino grueso y se produce como una complicación de tratamientos antibióticos. Se da ocasionalmente en ausencia de exposición a antibióticos; a menudo con presencia de un factor que predispone, p. ej. cirugía intestinal reciente, uremia, isquemia intestinal, quimioterapia, trasplante de médula ósea. El patógeno responsable es el "Clostridium difficile", un miembro de la flora normal cuyo sobrecrecimiento se produce ante la presencia de ciertos antibióticos o en ausencia de la flora bacterial normal debido a otros factores. Se cuenta con pruebas de cultivo y toxinas para identificar el C. difficile pero las pruebas microbiológicas positivas en ausencia de signos clínicos no respaldan un diagnóstico definitivo de colitis pseudomembranosa. Muchas notificaciones de diarrea asociadas con tratamiento antibiótico pueden no tener diagnósticos definitivos o pruebas específicas para colitis pseudomembranosa. La diarrea inducida por antibióticos no complicada suele aliviarse espontáneamente dentro de las dos semanas que siguen a la interrupción del tratamiento antibiótico. Para síntomas persistentes o colitis de Frank, puede ser necesaria una terapia agresiva para restablecer el balance de la flora intestinal dentro del tubo digestivo.
Definition (MDRITA) La colite pseudomembranosa è un grave processo necrotizzante che coinvolge l'intestino crasso e si manifesta come complicazione di una terapia antibiotica. Occasionalmente si manifesta in assenza di esposizione ad antibiotici, e in tal caso è spesso presente una condizione predisponente, ad es., recente intervento chirurgico intestinale, uremia, ischemia intestinale, chemioterapia, trapianto di midollo osseo. Il patogene responsabile è il "Clostridium difficile", componente della flora normale che cresce eccessivamente in presenza di certi antibiotici o in assenza della normale flora batterica a causa di altri fattori. Sono disponibili la coltura e i test delle tossine per identificare il C. difficile, ma un test microbiologico positivo in assenza di reperti clinici non supporta una diagnosi definitiva di colite pseudomembranosa. Molti eventi riportati di diarrea associati con terapia antibiotica possono non avere diagnosi definitive o test specifici per colite pseudomembranosa. La diarrea non complicata indotta da antibiotici generalmente si risolve spontaneamente entro due settimane dall'interruzione della terapia antibiotica. Per i sintomi persistenti, o colite ovvia, la terapia aggressiva potrebbe richiedere il ripristino dell'equilibrio della flora batterica nel lume del tratto intestinale.
Definition (MDRFRE) Une colite pseudomembraneuse est un processus nécrosant grave impliquant le gros intestin et résultant d'une complication d'antibiothérapie. Elle se produit occasionnellement en l'absence d'une exposition aux antibiotiques ; un état prédisposant est souvent présent, par exemple : intervention intestinale récente, urémie, ischémie intestinale, chimiothérapie, transplantation de moelle osseuse. Le pathogène responsable est « Clostridium difficile », un membre de la flore normale qui subit une croissance excessive en présence de certains antibiotiques ou en l'absence de flore bactérienne normale en raison d'autres facteurs. Des cultures et des tests de toxine sont disponibles pour identifier C. difficile mais des analyses microbiologiques positives en l'absence de constatations cliniques ne soutiennent pas un diagnostic définitif de colite pseudomembraneuse. Il arrive que beaucoup des rapports de diarrhée associée aux antibiotiques ne produisent pas un diagnostic définitif ou des tests spécifiques pour la colite pseudomembraneuse. Une diarrhée non compliquée associée aux antibiotiques disparaît en général spontanément dans les deux semaines suivant l'arrêt de l'antibiothérapie. Pour les symptômes qui persistent ou en cas de colite franche, un traitement agressif peut s'avérer nécessaire pour rétablir l'équilibre de la flore bactérienne à l'intérieur des voies intestinales.
Definition (MDRDUT) Pseudomembraneuze colitis is een ernstig necrotiserend proces in de dikke darm, dat optreedt als complicatie bij behandeling met antibiotica. Het treedt af en toe op in afwezigheid van blootstelling aan antibiotica; er is vaak een predisponerende aandoening aanwezig, bijv. een recente darmoperatie, uremie, intestinale ischemie, chemotherapie, beenmergtransplantatie. Het verantwoordelijke ziekteverwekkend organisme is 'Clostridium difficile', een lid van de normale flora die buitensporige groei vertoont in aanwezigheid van bepaalde antibiotica of in afwezigheid van normale bacteriële flora vanwege andere factoren. Er zijn kweken en toxinetests beschikbaar om C. difficile te identificeren, maar in afwezigheid van klinische bevindingen ondersteunt een positieve microbiologietest geen definitieve diagnose van pseudomembraneuze colitis. Vele meldingen van diarree die zich voordoet bij een behandeling met antibiotica bevatten wellicht geen definitieve diagnose of specifieke tests voor pseudomembraneuze colitis. Een ongecompliceerde door antibiotica opgewekte diarree verdwijnt gewoonlijk spontaan binnen twee weken na staking van antibioticabehandeling. Bij persisterende symptomen of uitgesproken colitis kan een agressieve behandeling nodig zijn om het evenwicht van de bacteriële flora binnen het lumen van het darmkanaal te herstellen.
Definition (MDRGER) Pseudomembranöse Kolitis stellt einen schweren, nekrotisierenden, den Dickdarm betreffendenr Prozess dar und erscheint als Komplikation bei der Behandlung mit Antibiotika. In manchen Fällen tritt diese Kolitis in Abwesenheit von Exposition gegenüber Antibiotika auf; oft besteht ein prädisponierender Zustand, z. B. vor kurzem durchgeführte Darmoperation, Urämie, Darmischämie, Chemotherapie, Knochenmarkstransplantation. Das verantwortliche Pathogen ist „Clostridium difficile", ein Mitglied der bakteriellen Normalflora, das in Gegenwart von Antibiotika oder in Abwesenheit bakterieller Normalflora verursacht durch andere Faktoren überhand nimmt. Kulturund Toxintests stehen zum Nachweis von C. difficile zur Verfügung, jedoch unterstützt selbst mehr als ein mikrobiologischer Test in Abwesenheit klinischer Befunde keine definitive Diagnose einer pseudomembranösen Kolitis. Viele Berichte einer Diarrhoe, die mit einer Therapie mit Antibiotika assoziiert werden, können möglicherweise keine definitiven Diagnosen oder spezifischen Tests für pseudomembranöse Kolitis enthalten. Gewöhnlich hört eine komplikationsfreie, durch Antibiotika verursachte Diarrhoe innerhalb von zwei Wochen nach Absetzen der Antibiotika spontan auf. Im Falle von persistenten Symptomen oder einer nicht-infektiösen Kolitis, kann eine aggressive Behandlung erforderliche sein, um das Gleichgewicht der bakteriellen Flora im Lumen des Gastrointestinaltraks wieder herzustellen.
Definition (MDRPOR) A colite pseudomembranosa é um processo grave e necrosante que afecta o intestino grosso e ocorre como uma complicação de tratamento com antibiótico. Ocasionalmente, ocorre na ausência de exposição a antibióticos; com frequência, existe um factor de predisposição, p. ex., cirurgia intestinal recente, uremia, isquemia intestinal, quimioterapia, transplante de medula óssea. O patogénio responsável é o "Clostridium difficile", um membro da flora normal cujo sobrecrescimento se produz na presença de certos antibióticos ou na ausência da flora bacteriana normal devido a outros factores. Existem testes disponíveis de cultura e toxinas para identificar o C. Difficile, mas o(s) teste(s) microbiológico(s) positivo(s) na ausência de sinais clínicos não corrobora(m) um diagnóstico definitivo de colite pseudomembranosa. Muitas notificações de diarreia associadas ao tratamento com antibiótico podem não ter diagnósticos definitivos ou testes específicos para a colite pseudomembranosa. A diarreia sem complicações e induzida por antibióticos costuma acalmar espontaneamente dentro das duas semanas que se seguem à interrupção do tratamento com antibiótico. Para sintomas persistentes ou colite de Frank, pode ser necessário um tratamento agressivo para restabelecer o equilíbrio da flora intestinal dentro do tubo digestivo.
Definition (MDRJPN) 偽膜性大腸炎は大腸を侵す重度の壊死性の疾患であり、抗生物質療法の合併症として起こる。時には抗生物質への曝露がなくても発症することがある：疾病素因が存在することが多い（例、最近の腸の外科手術、尿毒症、腸管虚血、化学療法、または骨髄移植）。原因となる病原体は、ある種の抗生物質の存在下、あるいは、他の要因によって正常な細菌叢の不在下において過剰増殖する正常細菌叢のメンバーである「Clostridium difficile（クロストリジウム-ディフィシレ）」である。C. difficileの特定には培養および毒性検査が有用であるが、臨床所見がない場合の細菌陽性結果は偽膜性大腸炎の確定診断を裏付けるものではない。抗生物質療法に関連する下痢の多数の報告からは、偽膜性大腸炎の確定診断や特異的検査は行えないと考えられる。合併症のない抗生物質誘発性の下痢は、通常では抗生物質の中止後2週間以内に自然に消失する。持続する症状や大腸炎の場合には、腸管腔内の細菌叢バランスを回復するための積極的治療が必要である。
Concepts Classification (T185)
English Pseudomembranous colitis (SMQ)
Dutch Pseudomembraneuze colitis (SMQ)
French Colite pseudomembraneuse (SMQ)
German Pseudomembranoese Kolitis (SMQ)
Italian Colite pseudomembranosa (SMQ)
Portuguese Colite pseudomembranosa (SMQ)
Spanish Colitis pseudomembranosa (SMQ)
Czech Pseudomembránová kolitida (SMQ)
Japanese 偽膜性大腸炎（ＳＭＱ）
Hungarian Pseudomembranosus colitis (SMQ)
Derived from the NIH UMLS (Unified Medical Language System)

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