Infectious Gastroenteritis and Colitis

Infectious Gastroenteritis and Colitis Jennifer Newton, M.D. Department of Internal Medicine University of Washington Boise Track December 1, 2009 (www.poopreport.com)

Outline Introduction Pathophysiology Clinical Presentation Clinical Evaluation and Diagnostic Approach Treatment Specific Pathogens

Why do I care??? Developing Countries 20-25% mortality in children <5 yo Leads to cognitive and physical developmental delay United States each year 200-300 million episodes 73 million MD visits 1.8 million hospitalizations Approx $6 BILLION spent Foodborne diarrheal illness is increasing

Pathophysiology Major Mechanisms of Diarrhea: Decreased absorption Increased secretion Increased luminal osmolality Changes in gut motility Mechanisms of Enteropathogens: Enterotoxin production (V. cholera, ETEC) Cytotoxin production (C. difficile, STEC, Shigella) Preformed toxin (S. aureus, B. cereus) Enteroadherence (EAEC, DAEC, EPEC) Mucosal invasion (Shigella, Salmonella, Campy, EIEC) Penetration and proliferation in the submucosa (Salmonella, Yersinia) Others intestinal secretogogues, neuronal pathways

Your clinic A 56yo M presents w/ 2 days of bloody diarrhea following 2 days of watery diarrhea. No abd pain or fever. No recent ABx or travel. On exam, he is afebrile, w/ mild nonspecific lower abd tenderness and +BS. Labs notable for normal WBC and many fecal leukocytes.

What do you do next? A) Request a stool cx and, on the basis of the result, decide on the necessity of ABx B) Initiate empiric ABx therapy while awaiting stool cx C) Initiate empiric ABx therapy without performing stool cx D) Flexible sigmoidoscopy E) Colonoscopy

Food Poisoning - Vomiting 4-8 hrs after ingestion S. aureus, B. cereus - N/V & Diarrhea 8-12 hrs after ingestion C. perfringens or B. cereus Clinic Presentation Most infectious diarrhea is brief (24-48h), self-limited, and managed by patients alone Small Intestinal Disease Ileocolonic Disease Diffuse periumbilical pain Large volume stools Watery stools Malabsorption & dehydration Lower abdominal pain Small volume stools May be bloody Tenesmus

Clinical Evaluation Volume status Severity of illness Epidemiologic clues Is diagnostic evaluation appropriate?

Volume Status

Severity of Illness Prolonged illness Illness not improving after 48 hrs >6 stools per day Volume depletion Bloody or dysenteric stools Severe abd pain in pts >50 yo

Epidemiologic Clues Travel History Recent Hospitalizations Underlying Medical Illnesses Sexual History Exposure to daycare Ingestion of unsafe foods Ingestion of untreated fresh water* Exposure to animals Sick contacts Recent antibiotics

Is Diagnostic Testing Indicated? Individuals Severe disease Systemic symptoms Illness lasting >1 week Elderly and immunocompromised Public Health Infection Control Suspected Outbreak Persons with high risk to transmit infections

Ok, Diagnostic testing is indicated what do I order? Selective testing based on epidemiologic clues (i.e. Giardia Ag) Fecal Leukocytes and Lactoferrin Assay still debated Stool Culture C. difficile toxin assays or culture Stool for Ova and Parasites

Treatment Rehydration Oral Rehydration Solutions Reduced-osmolarity ORS Resistant starches? Intravenous fluids Electrolyte Repletion and Nutrition Monitor and replete electrolytes Continue diet (BRAT or breastfeeding/formula) Zinc supplementation in children

Reduced-Osmolarity Oral Rehydration Solution STANDARD REDUCED meq or mmol/l meq or mmol/l Glucose 111 75 Sodium 90 75 Chloride 80 65 Potassium 20 20 Citrate 10 10 Osmolarity 311 245

Treatment Antidiarrheals bismuth subsalicylate and loperamide Generally safe in combination with antimicrobials (Adults) AVOID IN: children, adults w/ severe bloody or inflammatory diarrhea, severe colitis or C. difficile infection

Treatment Antimicrobials Due to risks of ABx therapy, awaiting culture results is best Empiric Treatment: Severe illness requiring hospitalization (esp. ICU) Moderate-severe traveler s diarrhea Elderly or immunocompromised hosts Suspected C. difficile colitis with severe disease Suspected shigellosis Persistent diarrhea w/ suspected Giardia

Specific Pathogens Small Intestinal Ileocolonic Viral Viral Calciviruses CMV Rotavirus Enteric adenovirus Bacterial Bacterial ETEC, EPEC, EAEC, DAEC Vibrio Cholera Listeria monocytogenes C. perfringens S. aureus Parasites Giardia lamblia Cryptosporidium Microsporidium Cyclospora Isospora Adenovirus Salmonella Shigella Campylobacter STEC or EHEC, EIEC C. difficile Yersinia Non-cholera vibrios Plesiomonas & Aeromonas Tuberculosis Klebsiella oxytoca C. perfringens S. aureus Parasites E. histolytica T. trichiura Balantidium coli Blastocystis hominis

Case 65yo M admitted with 5 days of diarrhea, bloody the last 2 days. He is stable overnight with IVF, and is afebrile. Labs on admission and this AM are as follows: 12.9 198 18 AST 44 10.2 19.5 110 AST 110 143 31 ALT 32 139 45 ALT 31 4.0 1.1 3.6 1.5

Which of the following organisms is most likely? A) Yersinia B) Toxigenic E. coli C) Norwalk-like virus (Norovirus) D) C. difficile E) E. coli O157:H7 (STEC)

Shiga-toxin E. coli Over 400 serotypes, only 10 cause disease Majority is O157 strains. Reservoir = Ruminants STEC produces Stx 1 and Stx 2 Sx: Biphasic diarrhea watery then bloody absent or low-grade fever O157 strains often localize to R colon Complications: TTP/HUS (5-10%) Dx: Stool Cx, specialized testing for O157, and EIA for Stx Stool may lack fecal leukocytes Tx: Supportive. Future antibiotics? Rifaximin, Azithromycin, Fosfomycin

Shigella Four species: S. dysenteriae most common worldwide S. sonnei most common in U.S. Humans are only natural host Highly contagious - <100 organisms Sx: Biphasic 2 day prodrome of constitutional sx s and secretory (watery) diarrhea Dysentery, fever, abd cramps, tenesmus Complications intestinal perforation, toxic megacolon, dehydration and metabolic derangements, sepsis, HUS/TTP, Reactive arthritis Dx: Stool Cx Get susceptibility tests! Tx: ORT/IVF and TMP-SMX (U.S.) or FQ (outside U.S.)

Salmonella enterica Nontyphoidal S. typhimurium, S. enteritidis most common in U.S. Transmission: Contaminated foods (raw meat, eggs, fresh produce, milk) Exposure to animals Sx: N/V then cramps & diarrhea Complications (5-10%) Bacteremia, meningitis, endovascular lesions Risk Factors: Hemoglobinopathies, corticosteroids, IBD, immunosuppression, achlorhydria and extremes of age Dx: stool cx, get sensitivities! Tx: Supportive care ABx: severe sx s, systemic/invasive disease, severe comorbidities, and patients w/ risk factors for invasive disease Ciprofloxacin, ceftriaxone, or azithromycin

Campylobacter Most common cause of diarrhea worldwide. U.S. C. jejuni most common Transmission: contaminated food (poultry, eggs, milk), water or fecal-oral spread Sx: cramping, nausea, anorexia and watery or bloody diarrhea. Resolves within a week. Mimics appendicitis Complications Post-infectious IBS, reactive arthritis, Guillain-Barré syndrome Dx: Stool Cx Tx: Mild-moderate: Supportive Severe or >1 week: Macrolides (FQs can be used, but increasing resistant strains)

Case 74yo F w/ DM2 presents w/ 2 weeks of watery diarrhea; passing 6-8 stools/day and occasional nocturnal diarrhea. +Nausea. No vomiting, bloody stools or fever. Recently switched from metformin to insulin. 6 weeks ago completed a course of ciprofloxacin for UTI. On exam, VSS, abd with mild nonspecific tenderness. Studies notable for + fecal leukocytes and negative C. difficile toxin by ELISA.

What would you do next? A) Initiate treatment with loperamide and titrate to symptom control B) Prescribe prednisone 40mg daily C) Prescribe metronidazole 500mg TID for 10 days D) Prescribe vancomycin 125mg QID for 10 days E) Send 2 additional stool samples for C. difficile toxin testing

C. Difficile infection (CDI) Both Nosocomial and Community-acquired Pathogenesis: enterotoxin A and cytotoxin B NAPI/B1: a new strain w/ increased production of toxins A and B, produces a binary toxin and FQ-resistance Sx: watery (rarely bloody) diarrhea, lower abd cramping, fever Severe Disease: severe pain, abd distension, hypovolemia, lactic acidosis, and marked leukocytosis (WBC>15) Predictors of Mortality: WBC >35 or <4, bandemia (>10%), age>70, immunosuppression and cardiorespiratory failure Dx: Who? Hospitalized, institutionalized, recent ABx, and now communityacquired. Depends on your facility: C.diff Ag w/ confirmatory toxin A and/or B by EIA or PCR If clinical suspicion is high, treat anyway

CDI Treatment Discontinuation of offending antibiotic (if possible) AVOID antidiarrheals Mild-Moderate: Metronidazole 250mg PO QID x 10-14 days Metronidazole 500mg PO TID x 10-14 days Vancomycin 125mg PO QID x 10-14 days* Severe: Vancomycin 125mg PO QID x 10-14 days Metronidazole 500mg IV q6-8 hrs Vancomycin via NGT or rectally Colectomy

Case continued Pt tested positive for C. difficile toxin. Two weeks ago, she completed a 10 day course of metronidazole 500mg PO TID. She initially noted improvement in her symptoms, but the diarrhea recurred 1 week ago. Repeat C. difficile toxin is positive.

What would you recommend now? A) Metronidazole 500mg PO TID x 14 days B) Vancomycin 125mg PO QID x 14 days C) Vancomycin 250mg PO QID x 14 days, followed by a taper D) Vancomycin 250mg PO QID x 14 days in combination with Saccharomyces boulardii E) Bacteriotherapy

Recurrent CDI Following initial treatment, 15-20% will develop recurrent CDI Usually occurs 5-8 days after completing initial therapy Risk Factors: Older age, intercurrent ABx, renal disease, prior recurrences of CDI Recurrence Resistance Treatment No Standard Regimen Repeat same or alternate antibiotic Vancomycin pulses and/or tapers for extended duration Vancomycin x 2 weeks then Rifaximin x 2 weeks High dose vancomycin in combination with Saccharomyces boulardii (NOT in immunosuppressed) Bacteriotherapy Fecal enemas Colonoscopic delivery of fecal material NG tube delivery of fecal material

C. Difficile negative nosocomial diarrhea Area of active study Think about: Klebsiella oxytoca MRSA Clostridium perfringens

Viral Gastroenteritis Most common cause of infectious diarrhea in the U.S. Sx: Dehydrating diarrhea, vomiting, +/- fever Typically resolves within a few days Etiology: Pediatrics: Rotavirus and Noroviruses Adults: Noroviruses Dx: Based on symptoms Tx: Supportive Vaccines: Infants: 1 of 2 rotavirus vaccines Adults: norovirus vaccine in development

Conclusions Infectious diarrhea is a major cause of morbidity and mortality worldwide. In the U.S., contributes to millions of healthcare visits and billions in cost. Classify as SI or IC to help identify pathogen Not everyone needs a workup. Viral gastroenteritis is the most common cause of infectious diarrhea in the U.S. When in doubt, it is best to wait for stool cultures before treatment Avoid ABx therapy in STEC and Salmonella Check frequently updated sources for antimicrobial sensitivities

Special Thanks Christina Surawicz, MD, MACG Professor of Medicine University of Washington Chief, Gastroenterology Harborview Medical Center

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