Clostridium difficile infection resident survival guide

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Clostridium difficile infection

Overview

Diagnostic Criteria

Classification of Disease Severity

Risk Factors

Complete Diagnostic Approach

Management

Dos and Don'ts

Guidelines and Resources

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

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 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 C. difficile infection.

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 C. difficile infection include:[3]

Classification of Disease Severity

American College of Gastroenterology (ACG)

Classification of disease severity:[4]

  • 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

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:[5]

  • 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:[6]

Characteristics that correlate with severity of colitis:[7]

  • 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)
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

Risk Factors

The most important risk factor remains antibiotic use. Other established risk factors include:[8]

Use of the following antibiotics has been associated with C. difficile infection:[9]

  • 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; DC, differential count; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction; 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

  • Characterize the symptoms:
  • Other relevant history:
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Other Investigation

Positive results of either EIA or NAAT should prompt treatment.

  • GDH (high sensitivity, low specificity): screening test
  • EIA for toxins (low sensitivity, high specificity): confirmatory test
  • NAAT (high sensitivity, high specificity): standard diagnostic test
 
 

Management

Asymptomatic carrier

  • No treatment indicated

Mild disease

Close outpatient monitoring without the administration of antibiotics

Moderate disease

  • Consideration of hospitalization AND
  • Cessation of predisposing antibiotics AND
  • Hydration AND
  • Monitoring of clinical status AND
  • Administration of metronidazole (500 mg three times per day)
    OR
Administration of vancomycin (125 mg orally four times per day for 14 days)

Severe disease

  • Hospitalization AND
  • Oral or nasogastric vancomycin (500 mg four times per day) with or without intravenous metronidazole (500 mg three times per day)
    OR
Oral fidaxomicin (200 mg twice a day for 10 days) if the risk of recurrence is high

Complicated disease

First recurrence

  • Oral vancomycin (125 mg four times per day for 14 days)
    OR
Oral fidaxomicin (200 mg twice a day for 10 days)

Second or further recurrence

Dos and Don'ts

Dos

Don'ts

  • Do NOT test for C. difficile in a patient without diarrhea.
  • Do NOT repeat test if the results are negative.
  • Do NOT perform test of microbiological cure.
  • Do NOT treat asymptomatic carriage.
  • Do NOT administer antiperistaltic agents to patients with suspected or confirmed C. difficile infection.

Guidelines and Resources

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)[11]
  • Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)[12]

American College of Gastroenterology (ACG)

  • Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)[13]

Association for Professionals in Infection Control and Epidemiology (APIC)

  • Preventing Clostridium difficile infections (2011)[14]

Eastern Association for the Surgery of Trauma (EAST)

  • Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)[15]

American Society of Colon and Rectal Surgeons (ASCRS)

  • Practice Parameters for the Management of Clostridium difficile Infection (2015)[16]

European Society of Clinical Microbiology and Infectious Diseases (ESCMID)

  • Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)[17]

American Academy of Pediatrics (AAP)

  • Policy Statement: Clostridium difficile Infection in Infants and Children (2013)[18]

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. 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)
  5. 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)
  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. 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)
  8. Khanna, Sahil; Pardi, Darrell S. (2012-11). "Clostridium difficile infection: new insights into management". Mayo Clinic Proceedings. 87 (11): 1106–1117. doi:10.1016/j.mayocp.2012.07.016. ISSN 1942-5546. PMC 3541870. PMID 23127735. Check date values in: |date= (help)
  9. 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.
  10. 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.
  11. 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)
  12. 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)
  13. 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)
  14. 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)
  15. 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)
  16. 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)
  17. 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)
  18. Schutze, Gordon E.; Willoughby, Rodney E.; Committee on Infectious Diseases; American Academy of Pediatrics (2013-01). "Clostridium difficile infection in infants and children". Pediatrics. 131 (1): 196–200. doi:10.1542/peds.2012-2992. ISSN 1098-4275. PMID 23277317. Check date values in: |date= (help)

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