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)

B)

C)

D) E)

Request a stool cx and, on the basis of the result, decide on the necessity of ABx Initiate empiric ABx therapy while awaiting stool cx Initiate empiric ABx therapy without performing stool cx Flexible sigmoidoscopy Colonoscopy

What do you do next?

A)

B)

C)

D) E)

Request a stool cx and, on the basis of the result, decide on the necessity of ABx Initiate empiric ABx therapy while awaiting stool cx Initiate empiric ABx therapy without performing stool cx Flexible sigmoidoscopy Colonoscopy

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

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

Clinical Evaluation

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

Volume Status

Volume Status

Volume Status

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 travelers diarrhea Elderly or immunocompromised hosts Suspected C. difficile colitis with severe disease Suspected shigellosis Persistent diarrhea w/ suspected Giardia

Specific Pathogens

Small Intestinal
Viral

Ileocolonic
Viral

Bacterial

Calciviruses Rotavirus Enteric adenovirus ETEC, EPEC, EAEC, DAEC Vibrio Cholera Listeria monocytogenes C. perfringens S. aureus Giardia lamblia Cryptosporidium Microsporidium Cyclospora Isospora

Parasites

CMV Adenovirus

Bacterial

Parasites

Salmonella Shigella Campylobacter STEC or EHEC, EIEC C. difficile Yersinia Non-cholera vibrios Plesiomonas & Aeromonas Tuberculosis Klebsiella oxytoca C. perfringens S. aureus

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 18 143 4.0 31 1.1 AST 44 ALT 32 10.2 110 19.5 139 3.6 45 1.5 AST 110 ALT 31

Which of the following organisms is most likely?

A) B) C) D) E)

Yersinia Toxigenic E. coli Norwalk-like virus (Norovirus) C. difficile E. coli O157:H7 (STEC)

Which of the following organisms is most likely?

A) B) C) D) E)

Yersinia Toxigenic E. coli Norwalk-like virus (Norovirus) C. difficile E. coli O157:H7 (STEC)

Shiga-toxin E. coli

Over 400 serotypes, only 10 cause disease Reservoir = Ruminants STEC produces Stx 1 and Stx 2 Sx:
Majority is O157 strains.

Complications: Dx:

Biphasic diarrhea watery then bloody absent or low-grade fever O157 strains often localize to R colon TTP/HUS (5-10%)

Tx: Supportive. Future antibiotics? Rifaximin, Azithromycin, Fosfomycin

Stool Cx, specialized testing for O157, and EIA for Stx Stool may lack fecal leukocytes

Shigella

Four species:

Humans are only natural host Highly contagious - <100 organisms Sx: Biphasic

S. dysenteriae most common worldwide S. sonnei most common in U.S.

Complications

2 day prodrome of constitutional sxs and secretory (watery) diarrhea Dysentery, fever, abd cramps, tenesmus 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.)

Salm onella enterica

Nontyphoidal

Transmission:

S. typhimurium, S. enteritidis most common in U.S. Contaminated foods (raw meat, eggs, fresh produce, milk) Exposure to animals

Sx: N/V then cramps & diarrhea Complications (5-10%)

Dx: stool cx, get sensitivities! Tx: Supportive care

Bacteremia, meningitis, endovascular lesions Risk Factors: Hemoglobinopathies, corticosteroids, IBD, immunosuppression, achlorhydria and extremes of age

ABx: severe sxs, 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-Barr 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) B) C) D) E)

Initiate treatment with loperamide and titrate to symptom control Prescribe prednisone 40mg daily Prescribe metronidazole 500mg TID for 10 days Prescribe vancomycin 125mg QID for 10 days Send 2 additional stool samples for C. difficile toxin testing

What would you do next?

A) B) C) D) E)

Initiate treatment with loperamide and titrate to symptom control Prescribe prednisone 40mg daily Prescribe metronidazole 500mg TID for 10 days Prescribe vancomycin 125mg QID for 10 days 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 Sx:

NAPI/B1: a new strain w/ increased production of toxins A and B, produces a binary toxin and FQ-resistance watery (rarely bloody) diarrhea, lower abd cramping, fever severe pain, abd distension, hypovolemia, lactic acidosis, and marked leukocytosis (WBC>15) WBC >35 or <4, bandemia (>10%), age>70, immunosuppression and cardiorespiratory failure 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

Severe Disease:

Predictors of Mortality: Dx:

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* Vancomycin 125mg PO QID x 10-14 days Metronidazole 500mg IV q6-8 hrs Vancomycin via NGT or rectally Colectomy

Severe:

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) B) C)

D)

E)

Metronidazole 500mg PO TID x 14 days Vancomycin 125mg PO QID x 14 days Vancomycin 250mg PO QID x 14 days, followed by a taper Vancomycin 250mg PO QID x 14 days in combination with Saccharomyces boulardii Bacteriotherapy

What would you recommend now?

A) B) C)

D)

E)

Metronidazole 500mg PO TID x 14 days Vancomycin 125mg PO QID x 14 days Vancomycin 250mg PO QID x 14 days, followed by a taper Vancomycin 250mg PO QID x 14 days in combination with Saccharomyces boulardii Bacteriotherapy

Recurrent CDI

Following initial treatment, 15-20% will develop recurrent CDI Usually occurs 5-8 days after completing initial therapy Risk Factors: Recurrence Resistance Treatment No Standard Regimen

Older age, intercurrent ABx, renal disease, prior recurrences of CDI

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

nosocomial diarrhea

C. Difficile negative
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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