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Clostridium difficile infection

Overview

Diagnostic Criteria

Classification of Disease Severity

Risk Factors

Complete Diagnostic Approach

Management

  • Mild Disease
  • Moderate Disease
  • Severe Disease
  • Complicated Disease
  • First Recurrence
  • Second or Further Recurrence
  • Dos and Don'ts

  • Dos
  • Don'ts
  • Guidelines

    Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

    Overview

    Clostridium difficile infection is the leading cause to nosocomial diarrhea. Clinical presentation ranges across a broad spectrum from asymptomatic carriage, to diarrheal illness, to complicated disease hallmarked by pseudomembranous colitis, toxic megacolon, or bowel perforation. Diagnosis is established by the presence of diarrheal symptoms coupled with positive stool tests or endoscopic findings. Therapeutic approach and antibiotic choice should be stratified according to severity of disease and risk of recurrence.

    Diagnostic Criteria

    Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

    The diagnosis of C. difficile infection should be based on a combination of clinical and laboratory findings. A case definition for the usual presentation of CDI includes the following findings:[1]

    • The presence of diarrhea, defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours AND
    • A stool test result positive for the presence of toxigenic C. difficile or its toxins OR colonoscopic or histopathologic findings demonstrating pseudomembranous colitis.

    The same criteria should be used to diagnose recurrent CDI.

    European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

    Diagnosis of C. difficile infection is based on the following criteria:[2]

    • A combination of signs and symptoms, confirmed by microbiological evidence of C. difficile in stools, in the absence of another cause
      OR
    • Colonoscopic or histopathological findings demonstrating pseudomembranous colitis

    Diagnostic tests for CDI include:[3]

    • Enzyme immunoassay (EIA): glutamate dehydrogenase (GDH), toxins A and B
    • Nucleic acid amplification tests (NAAT): 16S ribosomal RNA, GDH genes, toxin genes
    • Cell culture cytoxicity assay (CCA)
    • Culture of toxigenic C. difficile

    Classification of Disease Severity

    Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

    Initial episode of C. difficile infection may be stratified by disease severity as follows:[4]

    • Mild-to-moderate disease
    Leukocytosis with WBC < 15,000 cells/mL AND serum creatinine < 1.5 times the premorbid level
    • Severe disease
    Leukocytosis with WBC ≥ 15,000 cells/mL OR serum creatinine ≥ 1.5 times the premorbid level
    • Severe, complicated disease
    Hypotension or shock, ileus, megacolon

    European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

    Severe disease is defined as an episode of C. difficile infection with:[5]

    • One or more specific signs and symptoms of severe colitis
      OR
    • A complicated course of disease, with significant systemic toxin effects and shock, resulting in need for ICU admission, colectomy, or death.

    Characteristics that correlate with severity of colitis:[6]

    • Physical examination
    Fever (core body temperature > 38.5°C)
    Rigors (uncontrollable shaking and a feeling of cold followed by a rise in body temperature)
    Hemodynamic instability including signs of distributive shock
    Respiratory failure requiring mechanical ventilation
    Signs and symptoms of peritonitis
    Signs and symptoms of colonic ileus
    • Laboratory investigations
    Marked leukocytosis (leukocyte count > 15,000 cells/mL)
    Marked left shift (band neutrophils > 20% of leukocytes)
    Rise in serum creatinine (> 50% above the baseline)
    Elevated serum lactate (≥ 5 mmol/L)
    Markedly reduced serum albumin (< 3 mg/dl)
    • Colonoscopy or sigmoidoscopy
    Pseudomembranous colitis
    • Imaging
    Distention of large intestine (> 6 cm in transverse width of colon)
    Colonic wall thickening including low-attenuation mural thickening
    Pericolonic fat stranding
    Ascites not explained by other causes

    American College of Gastroenterology (ACG)

    Classification of disease severity:[7]

    • Mild disease
    Diarrhea as the only symptom
    • Moderate disease
    Diarrhea but without additional symptoms/signs meeting the definition of severe or complicated disease
    • Severe disease
    Hypoalbuminemia (serum albumin < 3 g/dl) AND
    WBC ≥ 15,000 cells/mL OR abdominal tenderness without criteria of complicated disease
    • Complicated disease
    Any of the following attributable to C. difficile infection:
    Admission to intensive care unit
    Hypotension with or without required use of vasopressors
    Fever ≥ 38.5°C
    Ileus (acute nausea, emesis, sudden cessation of diarrhea, significant abdominal distention, or radiological signs consistent with disturbed intestinal transit)
    Mental status changes
    WBC ≥ 35,000 cells/mL or < 2,000 cells/mL
    Serum lactate levels > 2.2 mmol/l
    Any evidence of end organ failure
    • Recurrent disease
    Recurrence within 8 weeks of completion of therapy

    Risk Factors

    The most important risk factor remains antibiotic use. Use of the following antibiotics has been associated with C. difficile infection:[8]

    • Very common
    Clindamycin
    Ampicillin
    Amoxicillin
    Cephalosporins
    Fluoroquinolones
    • Somewhat common
    Penicillins
    Sulfonamides
    Trimethoprim
    Trimethoprim-Sulfamethoxazole
    Macrolides
    • Uncommon
    Aminoglycosides
    Bacitracin
    Metronidazole
    Teicoplanin
    Rifampin
    Chloramphenicol
    Tetracyclines
    Carbapenems
    Daptomycin
    Tigecycline

    Complete Diagnostic Approach

    Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBC, complete blood count; CMV, cytomegalovirus; DC, differential count; HIV, human immunodeficiency virus; PET, positron emission tomography; s/o, suggestive of; SMA-7, sequential multiple analysis-7.

    Clostridium difficile Infection

    • Diarrhea (passage of 3 or more unformed stools in ≤ 24 hours) with microbiological evidence of C. difficile
    • Colonoscopic or histopathological findings demonstrating pseudomembranous colitis
     
     
     
     
     
     
     
     

    Focused History

     
     
     
     
     
     
     
     

    Physical Examination

     
     
     
     
     
     
     
     

    Imaging Study

     
     
     
     
     
     
     
     

    Other Investigation

     
     

    Management

    Dos and Don'ts

    Dos

    Don'ts

    Guidelines

    Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

    • Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals (2014)[9]
    • Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)[10]

    American College of Gastroenterology (ACG)

    • Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)[11]

    Association for Professionals in Infection Control and Epidemiology (APIC)

    • Preventing Clostridium difficile infections (2011)[12]

    Eastern Association for the Surgery of Trauma (EAST)

    • Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)[13]

    American Society of Colon and Rectal Surgeons (ASCRS)

    • Practice Parameters for the Management of Clostridium difficile Infection (2015)[14]

    European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

    • Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)[15]

    References

    1. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
    2. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
    3. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
    4. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
    5. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
    6. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)
    7. Surawicz, Christina M.; Brandt, Lawrence J.; Binion, David G.; Ananthakrishnan, Ashwin N.; Curry, Scott R.; Gilligan, Peter H.; McFarland, Lynne V.; Mellow, Mark; Zuckerbraun, Brian S. (2013-04). "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections". The American Journal of Gastroenterology. 108 (4): 478–498, quiz 499. doi:10.1038/ajg.2013.4. ISSN 1572-0241. PMID 23439232. Check date values in: |date= (help)
    8. Leffler, Daniel A.; Lamont, J. Thomas (2015-04-16). "Clostridium difficile infection". The New England Journal of Medicine. 372 (16): 1539–1548. doi:10.1056/NEJMra1403772. ISSN 1533-4406. PMID 25875259.
    9. Dubberke, Erik R.; Carling, Philip; Carrico, Ruth; Donskey, Curtis J.; Loo, Vivian G.; McDonald, L. Clifford; Maragakis, Lisa L.; Sandora, Thomas J.; Weber, David J.; Yokoe, Deborah S.; Gerding, Dale N. (2014-09). "Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update". Infection Control and Hospital Epidemiology. 35 Suppl 2: –48-65. ISSN 1559-6834. PMID 25376069. Check date values in: |date= (help)
    10. Cohen, Stuart H.; Gerding, Dale N.; Johnson, Stuart; Kelly, Ciaran P.; Loo, Vivian G.; McDonald, L. Clifford; Pepin, Jacques; Wilcox, Mark H.; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America (2010-05). "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)". Infection Control and Hospital Epidemiology. 31 (5): 431–455. doi:10.1086/651706. ISSN 1559-6834. PMID 20307191. Check date values in: |date= (help)
    11. Surawicz, Christina M.; Brandt, Lawrence J.; Binion, David G.; Ananthakrishnan, Ashwin N.; Curry, Scott R.; Gilligan, Peter H.; McFarland, Lynne V.; Mellow, Mark; Zuckerbraun, Brian S. (2013-04). "Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections". The American Journal of Gastroenterology. 108 (4): 478–498, quiz 499. doi:10.1038/ajg.2013.4. ISSN 1572-0241. PMID 23439232. Check date values in: |date= (help)
    12. Rebmann, Terri; Carrico, Ruth M.; Association for Professionals in Infection Control and Epidemiology, null (2011-04). "Preventing Clostridium difficile infections: an executive summary of the Association for Professionals in Infection Control and Epidemiology's elimination guide". American Journal of Infection Control. 39 (3): 239–242. doi:10.1016/j.ajic.2010.10.011. ISSN 1527-3296. PMID 21371783. Check date values in: |date= (help)
    13. Ferrada, Paula; Velopulos, Catherine G.; Sultan, Shahnaz; Haut, Elliott R.; Johnson, Emily; Praba-Egge, Anita; Enniss, Toby; Dorion, Heath; Martin, Niels D.; Bosarge, Patrick; Rushing, Amy; Duane, Therese M. (2014-06). "Timing and type of surgical treatment of Clostridium difficile-associated disease: a practice management guideline from the Eastern Association for the Surgery of Trauma". The Journal of Trauma and Acute Care Surgery. 76 (6): 1484–1493. doi:10.1097/TA.0000000000000232. ISSN 2163-0763. PMID 24854320. Check date values in: |date= (help)
    14. Steele, Scott R.; McCormick, James; Melton, Genevieve B.; Paquette, Ian; Rivadeneira, David E.; Stewart, David; Buie, W. Donald; Rafferty, Janice (2015-01). "Practice parameters for the management of Clostridium difficile infection". Diseases of the Colon and Rectum. 58 (1): 10–24. doi:10.1097/DCR.0000000000000289. ISSN 1530-0358. PMID 25489690. Check date values in: |date= (help)
    15. Debast, S. B.; Bauer, M. P.; Kuijper, E. J.; European Society of Clinical Microbiology and Infectious Diseases (2014-03). "European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection". Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 20 Suppl 2: 1–26. doi:10.1111/1469-0691.12418. ISSN 1469-0691. PMID 24118601. Check date values in: |date= (help)