1. The Diarrhea “Differential”
May, 2017
The Diarrhea “Differential”
Elizabeth (Liz) Holston, RN, MPH, CIC, CPHQ
Infection Prevention
Scripps Green Hospital

2. Agenda Objectives for this session Diarrhea: definitions
Diarrheal Illness: Why important?
Causes of diarrheal illness and commonly used testing
Challenges of testing for C difficile
Implications for Infection Prevention in the hospital setting
How to help your lab provide accurate results
Discussion

3. Objectives Define diarrhea
Identify frequent causes of diarrhea, infectious and non infectious, acute vs. chronic
Explain clinical importance of diarrheal illness and implications for infection prevention in the hospital setting
Identify commonly used lab tests for diarrheal illness, and the challenges of testing for C difficile

4. Impact of Diarrhea Globally: In USA
88% diarrhea associated deaths are attributable to unsafe water, poor sanitation, inadequate hygiene.
Most diarrheal deaths are preventable using simple low cost interventions
Second leading cause of death for children <5yrs. Diarrhea kills > children daily – more than AIDS, malaria and measles combined.
In USA
CDC estimated 76 million episodes/year of just foodborne illness, 325,000 hospitalizations, 5000 deaths/year
1.5 million OP visits, >1 billion $$ in direct medical costs.
Leading causes include Norovirus, non-typhoidal Salmonella.spp; C difficile, and Campylobacter

5. When is it “Diarrhea”? Diarrhea is :
“the passage of loose or watery stools, at least three times in a 24-hour period.”
Note the following categories based upon the duration of symptoms:
Acute — 14 days or fewer in duration
Persistent diarrhea — more than 14 but fewer than 30 days in duration
Chronic — more than 30 days in duration
Invasive diarrhea, often called dysentery: diarrhea with visible blood or mucus, in contrast to watery diarrhea. Dysentery is commonly associated with fever and abdominal pain.

6. Physiological Impact of Diarrhea
Depletes body fluids resulting in profound dehydration, electrolyte imbalance. (Which electrolytes?)
Diarrhea is especially dangerous for:
Children, elderly and immunocompromised (Why?)
Signs/Symptoms:
Excessive thirst
Dry mouth or skin
Weakness, dizziness, lightheaded
Fatigue
Dark colored urine

7. The Diarrhea Differential: Common Causes
Infectious:
Bacterial: C difficile, Shigella, enterotoxigenic E coli, Campylobacter, Salmonella, Shigella, protozoa (Giardia), Vibrio Cholerae
Viral: Norovirus, rotavirus, adenoviruses, astrovirus, cytomegalovirus, viral hepatitis
Non-infectious:
Digestive disorders:
Inflammatory bowel disease: Crohn’s disease, ulcerative colitis,
Celiac disease,
Irritable bowel syndrome
Food intolerance, artificial sweeteners
Lactose intolerance
Medications: cancer drugs, antibiotics
Surgery: e.g. post-cholecystectomy
Colon cancer

8. The Diarrhea Differential: Infectious or not?
Nausea and vomiting initially, then diarrhea ~ 4 hrs pp
Mouth sores, abdominal pain, diarrhea, weight loss and fever
Sudden onset, loose/explosive diarrhea, vomiting / feel ill. Resolves in about hours
Chronic/intermittent lower abdominal pain, diarrhea and/or constipation
Loose stools begin after use of antibiotics, stops after antibiotics stopped
After repeated antibiotic use, significant diarrhea begins after day 3 in the hospital.
Chronic diarrhea, may be bloody at times, diagnosed by colonoscopy. No fever
Occasional loose stool, flatulence, especially after eating.
Fever, bloody or mucoid stools

9. The Diarrhea Differential: Infectious or not?
Nausea and vomiting initially, then diarrhea ~ 4 hrs pp: Salmonella
Mouth sores, abdominal pain, diarrhea, weight loss and fever: Crohns disease
Sudden onset, loose/explosive diarrhea, vomiting / feel ill. Resolves in about hours. Noro virus
Chronic/intermittent lower abdominal pain, diarrhea and/or constipation. Irritable bowel syndrome
Loose stools begin after use of antibiotics, stops after antibiotics stopped. Antibiotic induced diarrhea
After repeated antibiotic use, significant diarrhea begins after day 3 in the hospital. C difficile
Chronic diarrhea, may be bloody at times, diagnosed by colonoscopy. No fever. Colitis
Occasional loose stool, flatulence, especially after eating. Food intolerance
Fever, bloody or mucoid stools: Inflammatory bowel infection

10. Causes of Diarrhea- acute onset
Features
Treatment
Infectious diarrhea
Viral infection
Loose stool, low-grade fever, feel ill
None, usually resolves within 48 hours
Bacterial infection
Fever (temperature >101°F or 38.4°C), bloody stools
Usually none, antibiotics in selected situations
Parasite
Not common in developed countries, may be seen in returning traveler or camper
Antibiotics in most cases
Non-infectious diarrhea
Antibiotics
Loose stool begins after antibiotic started, usually resolves with a few days after stopped
Usually none
Food intolerance (eg, lactose intolerance)
Diarrhea, abdominal pain, and/or gas after consuming food
Determine if food intolerance is the cause
Inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
Mouth sores, diarrhea, abdominal pain, weight loss, and fever
See a healthcare provider for full evaluation and treatment
Irritable bowel syndrome
Chronic lower abdominal pain, diarrhea and/or constipation
Symptomatic treatment
Celiac disease (gluten sensitivity)
None to diarrhea, weight loss, abdominal pain, gas
Complete avoidance of wheat, rye, barley

11. Enteric Pathogens Pathogen Small bowel Colon Bacteria Salmonella*
Escherichia coli¶
Clostridium perfringens
Staphylococcus aureus
Aeromonas hydrophila
Bacillus cereus
Vibrio cholerae
Campylobacter*
Shigella
Clostridium difficile
Yersinia
Vibrio parahaemolyticus
Enteroinvasive E. coli
Plesiomonas shigelloides
Klebsiella oxytoca(rare)
Virus
Rotavirus
Norovirus
Astrovirus
Cytomegalovirus*
Adenovirus
Herpes simplex virus
Protozoa
Cryptosporidium*
Microsporidium*
Cystoisospora
Cyclospora
Giardia lamblia
Entamoeba histolytica

12. Assessment and Testing
Patient History!
Enteric pathogens:
Shigella spp
Shiga Toxin Gene
E. coli O157:H7
Campylobacter spp. Undercooked poultry,
Salmonella spp.: (non-typhoidal) poultry, eggs, milk, also meat, fresh produce. (pet reptiles)
Yersinia
C difficile
Norovirus (Norwalk virus)
Other bugs/parasites:
Giardia
Hepatitis
CMV PCR
Stool leucocyte

13. C difficile Testing
•Enzyme immunoassay. (EIA) faster than other tests, lower sensitivity
•Polymerase chain reaction. (PCR) molecular test can rapidly detect the C. difficile toxin B gene in a stool sample and is highly accurate.
•GDH/EIA. Some hospitals use a glutamate dehydrogenase (GDH) in conjunction with an EIA test. GDH is a sensitive assay, but non specific, and usually followed by direct cytotoxin testing or culture.
•Cell cytotoxicity assay. A cytotoxicity test looks for the effects of the C. difficile toxin on human cells grown in a culture. Sensitive, but more cumbersome requires 24 to 48 hours for test results.

14. C difficile Testing: Colonization vs. Infection
Typical tests for C difficile and their weakness
Toxin + Antigen (EIA) Enzyme immunoassay
Toxin PCR (NAAT)
Neither of these are diagnostic by themselves.
Need clinical correlation
C difficile “Indeterminate” test results
Hospital Onset after day 3
What are hospitals doing to reduce # of HO cases due to likely colonization.

15. Implications for Infection Prevention
Transmission Precautions?
What type of precautions?
When?
How long?
Environmental considerations for cleaning?
What about hand hygiene?

16. How to help your lab provide accurate results
Timely collection
Proper labeling
Send it down fresh

17. Discussion