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GASTROENTERITIS

DISCLOSURE

Relevant relationships with commercial entities – Wyeth (received advisory board & speaker honoraria)

Potential for conflicts of interest within this presentation – fidaxomicin (which is an option to treat Clostridium difficile infection) is discussed in this presentation and is manufactured by Wyeth

Steps taken to review and mitigate potential bias – limited discussion to that included in current guidelines and peer reviewed literature

LEARNING OBJECTIVES

This lecture is designed to meet the following end-of-week learning objective:

1. Describe the etiologic agents, pathogenesis, clinical presentation, diagnostic tests, treatment, modes of transmission, and control measures involved in gastroenteritis

MODULE OBJECTIVES

By the end of this module, you should be able to:

1. Describe the etiology, pathogenesis, clinical presentation, diagnostic tests, treatment, modes of transmission and control for C. difficile, norovirus/rotavirus, and enteric bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia, shiga-toxin producing E. coli)

RECOMMENDED READING

Engleberg et al (eds.) Schaechter’s Mechanisms of Microbial Disease (5th Edition), Lippincott Williams & Wilkins 2013

- Chapters 60

GASTROENTERITIS

Inflammation of the gastrointestinal tract due to enteric pathogens

ENTERIC PATHOGENS

Bacteria

• Clostridium difficile

• Salmonella spp

• Shigella spp

• Campylobacter jejuni

• Yersinia enterocolitica

• Shiga-toxin producing E. coli (e.g. E. coli O157:H7)

• Enterotoxigenic E. coli

Viruses

• Norovirus, Rotavirus

Parasites

– Giardia, Entameoba histolytica, Cryptosporidium

PATHOGENESIS

Enterotoxin

interferes with absorptive function of intestinal villus e.g., enterotoxigenic E. coli.

Alteration of absorptive surface of villus tip via attaching mechanism or unknown

e.g., Cryptosporidium, Giardia, norovirus, rotavirus, shiga-toxin + E. coli.

Invasion of GI epithelium (inflammatory)

e.g., Salmonella, Shigella, Campylobacter, E. histolytica

Toxins A+B, spores but requires altered microbiota*

e.g., C. difficile

C. difficile Infection – requires altered microbiota

Asymptomatic

C. difficile

colonization

C. difficile

exposure

Antimicrobial

exposure

No

recurrent

disease

Recurrent

disease

~25%

~75% C. difficile

infection

(CDI)

Adapted from CID 1998;26:1027-103 and CMAJ 2004;171:51-58

SOURCE/TRANSMISSION

• Mode of Transmission: fecal-oral

• Exogenous source – food, water, person to person, contaminated fomites, and for C. difficile hospital/home environment* *most common cause of nosocomial gastroenteritis

• Inoculum size – varies with pathogens (i.e. inherent virulence) and susceptibility to gastric acid – Shigella – 101-2 CFU

– Salmonella - 106-9 CFU

CLINCAL PRESENTATION

• Acute onset anorexia, nausea, vomiting, diarrhea (bacterial, viral)

• Chronic diarrhea (parasitic)

PROGNOSIS

• Bacterial and viral gastroenteritis typically self-limited

• C. difficile infection typically needs treatment and even with treatment, recurrence and complications can occur

Overview of C. difficile Infection

C. difficile

infection

(CDI)

Uncomplicated

Complicated

• Paralytic ileus

• Septic shock

• Toxic

megacolon

• Perforation

ICU

admission

Colectomy

Death

• Mild/moderate

• Severe (Cr, WBC >15,

T>38.3oC, not improving after

5-6 days of tx)

Adapted from CID 1998;26:1027-103 and CMAJ 2004;171:51-58

Slide 13

Slide 14

Normal

Colon CDI colon

CDI colon

Normal

Colon

Slide 15

Megacolon

DIAGNOSIS

Send stool for testing as follows: • Bacteria:

– Bacterial culture - routinely rules out:

• Salmonella spp.

• Shigella spp.

• Campylobacter jejuni

• Shiga-toxin producing E. coli (e.g. E. coli O157:H7)

– C. difficile toxin detection (NAAT or EIA) • Viruses

– Electron microscopy, NAAT • Parasites

– Direct staining, enzyme immunoassay

TREATMENT

Non-C. difficile infections • Supportive care • Consider antimicrobials for bacterial causes if severe

disease or immunosuppressed (not with shiga-toxin producing E. coli given potential for precipitating hemolytic-uremic-syndrome)

For C. difficile infection (CDI) • Discontinue antimicrobials if not needed • Treat with metronidazole, vancomycin, fidaxomicin,

vancomycin taper, fecal microbiota transplantation*

TREATMENT OPTIONS FOR A FIRST EPISODE OF CDI

Mild/Moderate CDI

Oral metronidazole x10-14d

Severe CID

Oral vancomycin x10-14d

CID 2007;45:302-7; NEJM 2008;359;1932-40

Am J of Gastro 2013;108:478-498; ICHE 2010;31(5):431-55

TREATMENT OPTIONS FOR A FIRST EPISODE OF CDI

Complicated

Oral vancomycin x10-14d

Rectal vancomycin x10-14d

& IV metronidazole x10-14d

CID 2007;45:302-7; NEJM 2008;359;1932-40

Am J of Gastro 2013;108:478-498; ICHE 2010;31(5):431-55

TREATMENT OPTIONS FOR RECURRENT CDI

First recurrence

• Same regimen as initial episode (but if severe, use vancomycin)

Second recurrence

• Pulsed vancomycin

Third recurrence

• Consider fecal microbiota transplant (FMT)*

Am J of Gastro 2013;108:478-498; ICHE 2010;31(5):431-55

THE PROBLEM WITH RECURRENT CDI

Risk of recurrence increases

• Risk after 1st episode ~25%

• Risk after 1st recurrence ~45%

• Risk after 2nd recurrence ~65%

Clin Micro Infect 2012;18(Suppl 6):21-17

PREVENTION OF BACTERIAL GASTROENTRITIS

Community:

• Sanitation – clean water source, appropriate sewage handling

• Proper food handling and cooking

• Handwashing/Hand hygiene

- Wash your hands/perform hand hygiene before eating and after using toilet

• Avoid preparing food and sharing food if you are infected and don’t share food with someone who is infected or eat food prepared by them

PREVENTION OF BACTERIAL GASTROENTRITIS

Hospital Precautions:

• Use contact precautions for all pediatric inpatients and for adults inpatients who are incontinent or unable to adhere to hygienic toilet practices

• Ensure routine environmental cleaning of rooms and patient equipment

• Healthcare workers who are ill should stay home

PREVENTION OF C. difficile

Prevent suppression of normal flora:

– judicious use of antimicrobial agents (antimicrobial stewardship)

– ?probiotics if require antimicrobials Prevent exposure to C. difficile:

– Wash hands/perform hand hygiene before eating and after using the toilet

Hospital Precautions:

– Use contact precautions

– Ensure routine environmental cleaning of rooms and patient equipment with sporicidal agents

QUIZ

You are seeing your patient in follow-up after a recent elective surgery in which he had pre-operative antimicrobials; he’s been well since but has just developed acute onset watery diarrhea 10x/day; he has no sick contacts and does not BBQ

What is your most likely etiology?

QUIZ

Most likely organism:

– Clostridium difficile

KEY MESSAGES

1. Acute nausea/vomiting/diarrhea typical symptoms of gastroenteritis

2. The differential causative agents of gastroenteritis includes bacterial, viral, and parasitic pathogens

3. C. difficile infection has a unique pathogenesis in that it requires the normal microbiota to first be altered; it is the most common cause of nosocomial gastroenteritis

4. Most causes of diarrhea cases are self-limited

5. C. difficile infection is associated with recurrent episodes and severe complications

MODULE OBJECTIVES

By now you should be able to:

1. Describe the etiology, pathogenesis, clinical presentation, diagnostic tests, treatment, modes of transmission and control for C. difficile, norovirus/rotavirus, and enteric bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia, shiga-toxin producing E. coli)