“Don’t Drink the Water”: A Primer on Infectious Diarrhea Patty W. Wright, MD with appreciation to Ban Allos, MD March 2011

Objectives To familiarize participants with the causes, diagnostic work-up, and treatment of the most common etiologies of infectious diarrhea.

Foodborne-related Illness and Death in the U.S. Events per yearNumber Illnesses>76 million Hospitalizations>325,000 Deaths>5,000

Common Food- and Water-borne Pathogens Causing Diarrhea in the US Salmonella Campylobacter Shigella Listeria Vibrio E. coli O:157 Bacillus Clostridium S. aureus Rotaviruses Norwalk-like viruses Cyclospora Isospora Cryptosporidium Giardia

Case 1 A 19 year old female college student presents to the ED at 5 pm c/o the acute onset of N/V with abdominal cramps and mild diarrhea. She denies associated fevers. She ate at a local restaurant today at noon. She reports that several of her classmates have been ill over the past week with the “stomach flu”.

Case 1 What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Acute N/V +/- Diarrhea: Pathogens Pathogens that have preformed toxins –Cause onset of symptoms within 1-6 hours of ingestion –S. aureus –Bacillus cereus (short-incubation) “Winter Vomiting Disease” –Norwalk-like viruses –Rotavirus

Acute N/V +/- Diarrhea: Dx and Rx Typically resolves within hrs, without specific therapy No diagnostic work-up required Treat with anti-emetics and hydration, if needed

Classic Association/Outbreak Staphylococcus aureus – ham, cream-filled pastries

Classic Association/Outbreak Norwalk-like viruses – cruise ships, raw seafood

Case 2 A 45 year old male develops nausea, diarrhea, and abd cramps at bedtime. He denies any associated vomiting, fever, or blood in his stool. He reports that a friend from work, who at lunch with him at a local Chinese restaurant, is also ill with similar symptoms.

Case 2 What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Acute Diarrhea w/o Vomiting/Fever Pathogens that produce toxins in vivo –Bacillus cereus (long-incubation) –Clostridium perfringens Typically resolves within 24 – 48 hrs, without specific therapy No diagnostic work-up required Treat symptomatically

Classic Association/Outbreak Bacillus cereus – fried rice

Case 3 A 56 year old male with HTN presents to the clinic with a 2 day h/o diarrhea, abd cramps, and fever to 101. He denies blood in his stool or N/V. His wife also reports diarrhea over the past 24 hours. He denies any recent hospitalizations or antibiotic usage.

Case 3 What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Acute Diarrhea and Fever w/o Bloody Stool Pathogens that cause tissue invasion –Salmonella –Shigella –Campylobacter –Vibrio –Invasive E coli –Listeria

Acute Diarrhea and Fever w/o Bloody Stool For diarrhea > 1 day in duration or severe (dehydration, fever, blood) –Obtain additional exposure history –Check fecal WBC If + fecal WBC –Stool culture for pathogens –Consider testing for C diff toxin –Consider empiric abx (adults only)

Acute Diarrhea and Fever w/o Bloody Stool Treatment: –Hydration –Quinolones typically empiric treatment of choice for food-borne diarrhea –Azithromycin is alternative if cannot take quinolones or risk of resistant Campylobacter

Classic Association/Outbreak Salmonella – peanut butter

Classic Association/Outbreak Salmonella and Campylobacter – poultry and poultry products

Classic Association/Outbreak Vibrio – raw oysters (or wading in the Gulf of Mexico), especially in patients with hepatic dysfxn

Classic Association/Outbreak Listeria – refrigerated food items (cold cuts, prepared salads), soft cheeses

Classic Association/Outbreak Shigella – low infectious dose ( organisms), “cool, moist foods that require much handling after cooking”,

Classic Association/Outbreak Yersinia – pork, chitterlings

Case 4 A 23 year old female presents to the ED with 3 days of diarrhea. She reports that she initially had watery diarrhea, but that it has now turned grossly bloody. She reports severe abd cramps. She denies fever or N/V.

Case 4 What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Acute Bloody Diarrhea +/- Fever Pathogens that produce shiga toxin –Shigella dysenteriae –E coli O157:H7 Evaluation: –Fecal WBC –Stool culture for pathogens (including E coli O157:H7) –Consider testing for C diff toxin –CBC with diff, BMP

Acute Bloody Diarrhea +/- Fever Treatment –NaCl hydration and supportive care –AVOID antibiotics (especially trim-sulfa) –AVOID antimotility agents in all patients with diarrhea and High fever or Bloody diarrhea or Fecal WBC’s

Hemolytic Uremic Syndrome (HUS) Occurs in about 10% of pts with E coli O157:H7 Begins ~ 5-10 days after symptom onset Triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure Most common in kids < 4 yrs old Mortality rate 5-15% Older children and adults have poorer prognoses Na load most protective factor in the prevention of HUS in pts with E coli O157:H7

Classic Association/Outbreak: E. coli O157:H7 1.Food -Foods of bovine origin (hamburger, milk, etc.) -Fruits (apple cider) and vegetables contaminated with manure

Classic Association/Outbreak: E. coli O157:H7 2.Water -Contaminated drinking water -Swimming in contaminated pools and lakes 3.Direct person-to-person or animal-to-person spread -Daycare centers -Long-term care facilities -Petting zoos

Case 5 A 37 year old male presents to the clinic c/o 4 weeks of daily diarrhea with associated anorexia, fatigue, bloating, and nausea. He denies fevers, vomiting, or blood in his stool. He has lost about 7 pounds over the past month. He denies recent travel.

Case 5 What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Chronic Diarrhea (Non-bloody) Etiologies –Parasites –Tropical Sprue –Bacterial overgrowth syndromes –Non-infectious causes Food allergies Neoplasm and endocrine processes Functional disorders

Chronic Diarrhea (Non-bloody) Most common parasitic causes in US –Giardia –Cryptosporidium –Cyclospora –Isospora Giardia photos:

Chronic Diarrhea (Non-bloody) Diagnosis: –Fecal WBC –Wet mount for ova and parasites –Modified acid-fast stain to detect Cyclospora Isospora Cryptosporidium –Giardia antigen testing (stool) –HIV antibody testing Treatment specific for pathogen isolated

Classic Association/Outbreak Cryptosporidium – drinking water contaminated with manure after flooding Cyclospora – raspberries contaminated with bird feces

Chronic Bloody Diarrhea Inflammatory Bowel Disease (ulcerative colitis or Crohn's disease) most common cause Differential includes bowel ischemia, colon cancer, or polyps Infectious causes possible, but much less likely

Case 6 A 68 year old female with chronic sinusitis presents with fever to 100.7, malaise, abdominal pain, and severe diarrhea which started yesterday. She reports having 20 watery, non-bloody stools since her diarrhea began. Her current medications include a steroid nasal spray, loratidine, and omeprazole.

Case 6: What pathogens are on your differential? What diagnostic work-up would you perform? How would you treat the patient?

Clostridium difficile- Associated Disease Risk Factors for CDAD: –Antibiotic exposure Any abx within the prior 2 months –Prolonged hospitalization –Severity of underlying disease –Age > 65 years –GI surgery –PPI

Clostridium difficile- Associated Disease Spectrum of Disease –Asymptomatic carrier –Diarrhea without colitis –Colitis without pseudomembranes –Pseudomembranous colitis –Fulminant colitis

Clostridium difficile- Associated Disease Pseudomembranous Colitis

Clostridium difficile- Associated Disease Fulminant colitis –About 3% of cases –Signs and Symptoms Diffuse abd tenderness/distention, diarrhea, low BP, high fever, leukocytosis –Complications Ileus, toxic megacolon, bowel perforation, death

Clostridium difficile- Associated Disease Diagnosis –ELISA testing for toxins A and B May need to repeat to improve sensitivity –Cytotoxicity assays “Gold Standard”, but expensive & requires 48 hrs –Culture for C. diff Does not distinguish disease from colonization –Colonoscopy Risk for perforation

Clostridium difficile- Associated Disease Treatment of mild disease –Metronidazole po 500mg Q8hrs x days Treatment of moderate to severe disease (WBC > 15k or increasing cr) –Vancomycin po 125mg Q6hrs x days

Clostridium difficile- Associated Disease Treatment of severe disease (hypotension, obstruction, ileus, or perforation) –Metronidazole iv 500mg Q8hrs and vancomycin via NGT 500mg Q6hrs and/or vancomycin enema –Surgical consult Consider colectomy if rising WBC and lactate

Clostridium difficile- Associated Disease Recurrence –Occurs in 5-30% of patients –Rate does not vary with initial agent used –Can consider re-treatment with same agent –Consider vancomycin po pulse dosed ( mg Q 3days x 3 wks) or tapered –? Role of cholestyramine and probiotics ELISA not recommended as a test of cure in asymptomatic pts

Clostridium difficile- Associated Disease Prevention and Control –Avoid unnecessary antibiotic use –Hand washing with soap and water Avoid alcohol-based hand sanitizers for hand hygiene after seeing patients with known or suspected C. diff –Contact precautions for hospitalized pts –Clean pt environment with 1:10 dilution of bleach

Summary- Diarrhea Acute diarrhea with N/V will typically resolve within hrs without rx If diarrhea persists or is severe, evaluate with fecal WBC, cx, +/- C. diff Hydration and supportive care +/- abx for treatment Evaluate for parasites and HIV if chronic diarrhea

Summary- CDAD Wide spectrum of disease states Dx with ELISA testing for toxins A and B Rx mild disease w/ po metronidazole; Rx severe disease w/ po vancomycin; Rx w/ iv metro and NGT/pr vanc, if ileus Recurrence is common Use hand washing and contact precautions to prevent spread