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

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

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

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 >2000 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

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.

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

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

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 48-72 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

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 48-72 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

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

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

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

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.

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.

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

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

Discussion