Infectious Gastroenteritis and Colitis

Jennifer Newton, M.D.Department of Internal MedicineUniversity of Washington – Boise TrackDecember 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 sigmoidoscopyE) Colonoscopy

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 sigmoidoscopyE) Colonoscopy

Clinic Presentation

Small Intestinal Disease Ileocolonic Disease

Diffuse periumbilical pain Lower abdominal pain

Large volume stools Small volume stools

Watery stools May be bloody

Malabsorption & dehydration Tenesmus

Most infectious diarrhea is brief (24-48h), self-limited, and managed by patients alone

Food Poisoning- Vomiting 4-8 hrs after ingestion S. aureus, B. cereus- N/V & Diarrhea 8-12 hrs after ingestion C. perfringensor B. cereus

Clinical Evaluation

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

Volume Status

Volume StatusVolume 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 REDUCEDmEq or mmol/L mEq or mmol/L

Glucose 111 75Sodium 90 75Chloride 80 65

Potassium 20 20Citrate 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. difficileinfection

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

– Viral Calciviruses Rotavirus Enteric adenovirus

– Bacterial ETEC, EPEC, EAEC, DAEC Vibrio Cholera Listeria monocytogenes C. perfringens S. aureus

– Parasites Giardia lamblia Cryptosporidium Microsporidium Cyclospora Isospora

Ileocolonic– Viral

CMV Adenovirus

– Bacterial 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:

12.919818

143

1.1

31

4.0

11019.5

10.2

3.6

139

1.5

45

AST 44

ALT 32

AST 110

ALT 31

Which of the following organisms is most likely?

A) YersiniaB) Toxigenic E. coliC) Norwalk-like virus (Norovirus)D) C. difficileE) E. coli O157:H7 (STEC)

Which of the following organisms is most likely?

A) YersiniaB) Toxigenic E. coliC) Norwalk-like virus (Norovirus)D) C. difficileE) E. coli O157:H7 (STEC)

Which of the following organisms is most likely?

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 dailyC) Prescribe metronidazole 500mg TID for 10

daysD) Prescribe vancomycin 125mg QID for 10

daysE) Send 2 additional stool samples for C.

difficile toxin testing

What would you do next?

A) Initiate treatment with loperamide and titrate to symptom control

B) Prescribe prednisone 40mg dailyC) Prescribe metronidazole 500mg TID for 10

daysD) Prescribe vancomycin 125mg QID for 10

daysE) 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 community-

acquired.– 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 daysB) Vancomycin 125mg PO QID x 14 daysC) Vancomycin 250mg PO QID x 14 days,

followed by a taperD) Vancomycin 250mg PO QID x 14 days in

combination with Saccharomyces boulardiiE) Bacteriotherapy

What would you recommend now?

A) Metronidazole 500mg PO TID x 14 daysB) Vancomycin 125mg PO QID x 14 daysC) Vancomycin 250mg PO QID x 14 days,

followed by a taperD) Vancomycin 250mg PO QID x 14 days in

combination with Saccharomyces boulardiiE) 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, MACGProfessor of MedicineUniversity of WashingtonChief, GastroenterologyHarborview Medical Center

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