Clostridium difficile infection resident survival guide
Clostridium difficile infection |
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 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]
- 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 intensive care unit 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)
- 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. Other established risk factors include:[8]
- Advanced age
- Chemotherapy
- Chronic kidney disease
- Consumption of processed meat
- Contact with active carriers
- Cystic fibrosis
- Diabetes mellitus
- Hypoalbuminemia
- Immunosuppression, immunodeficiency, or human immunodeficiency virus
- Increased risk with prolonged use or multiple antibiotics
- Inflammatory bowel disease
- Liver cirrhosis
- Malignancy
- Malnutrition
- Nursing home or long-term care facility residence
- Presence of comorbid conditions
- Presence of gastrostomy or jejunostomy tube
- Previous gastrointestinal surgery or endoscopic procedure
- Previous hospitalization and prolonged length of hospital stay
- Solid organ or hematopoietic stem cell transplantation
- Use of proton pump inhibitors
Use of the following antibiotics has been associated with C. difficile infection:[9]
- Very common
- Somewhat common
- 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
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Focused History
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Physical Examination
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Laboratory Workup and Imaging Study
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Management
Asymptomatic carrier
- No treatment indicated
Mild disease
- Predisposing antibiotic cessation
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day)
OR
- Close outpatient monitoring without the administration of antibiotics
Moderate disease
- Consideration of hospitalization
- Cessation of predisposing antibiotics
- Hydration
- Monitoring of clinical status
- 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
- 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
- Antibiotics as for severe infection
- Surgical consultation for subtotal colectomy or a diverting ileostomy with vancomycin colonic lavage
- Consideration of fecal microbial transplantation or additional antibiotics
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
- Vancomycin in a tapered and pulsed regimen
OR - Fecal microbial transplantation
OR - Fidaxomicin (200 mg twice a day for 10 days)[10]
Dos and Don'ts
Dos
- Inform the laboratory when testing for Clostridium difficile from formed stools in a patient with ileus.
- Initiate empiric antibiotics regardless of the laboratory results when there is a high index of suspicion for C. difficile infection.
- Vancomycin should be delivered via enema to treat patients in whom oral antibiotics cannot reach a segment of the colon as in Hartman’s pouch, ileostomy, or colonic diversion.
- Test for C. difficile among patients with diarrhea in the context of malignancy, chemotherapy, immunosuppressive therapy, organ transplantation, cirrhosis, inflammatory bowel disease, or pregnancy.
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
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
- ↑ 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:
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(help) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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:
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(help) - ↑ 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:
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(help) - ↑ 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.
- ↑ 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.
- ↑ 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) - ↑ 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) - ↑ 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) - ↑ 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:
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(help) - ↑ 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:
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(help) - ↑ 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) - ↑ 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) - ↑ 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)