Sandbox cdi

# 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:
- 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:
- 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:
- 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:
- Mild-to-moderate disease
- Severe disease
- Severe, complicated disease

## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Severe disease is defined as an episode of C. difficile infection with:
- 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:
- Physical examination
- Laboratory investigations
- Colonoscopy or sigmoidoscopy
- Imaging

## American College of Gastroenterology (ACG)
Classification of disease severity:
- Mild disease
- Moderate disease
- Severe disease
- Complicated disease
- Recurrent disease

# Risk Factors
The most important risk factor remains antibiotic use.  Other established risk factors include:
- 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:
- Very common
- Somewhat common
- Uncommon

# 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.

# 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

## Moderate disease
- Consideration of hospitalization
- Cessation of predisposing antibiotics
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day) OR

## 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

## 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

## 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)

# 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 Hartmann'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)
- Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)

## American College of Gastroenterology (ACG)
- Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)

## Association for Professionals in Infection Control and Epidemiology (APIC)
- Preventing Clostridium difficile infections (2011)

## Eastern Association for the Surgery of Trauma (EAST)
- Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)

## American Society of Colon and Rectal Surgeons (ASCRS)
- Practice Parameters for the Management of Clostridium difficile Infection (2015)

## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
- Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)

## American Academy of Pediatrics (AAP)
- Policy Statement: Clostridium difficile Infection in Infants and Children (2013)