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, shigatoxin + 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 Antimicrobial exposure Asymptomatic C. difficile colonization C. difficile exposure C. difficile infection (CDI) ~75% ~25% No recurrent disease Recurrent disease 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 10 1-2 CFU Salmonella - 10 6-9 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 Mild/moderate Severe ( Cr, WBC >15, T>38.3 o C, not improving after 5-6 days of tx) Paralytic ileus Septic shock Toxic megacolon Perforation ICU admission Colectomy Death Adapted from CID 1998;26:1027-103 and CMAJ 2004;171:51-58
Slide 13
Normal Colon CDI colon Normal Colon CDI colon Slide 14
Megacolon Slide 15
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
Complicated Oral vancomycin x10-14d TREATMENT OPTIONS FOR A FIRST EPISODE OF CDI 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
First recurrence TREATMENT OPTIONS FOR RECURRENT CDI 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 2 nd recurrence ~65% Clin Micro Infect 2012;18(Suppl 6):21-17
Community: PREVENTION OF BACTERIAL GASTROENTRITIS 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 Hospital Precautions: GASTROENTRITIS 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 preoperative 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)