Infectious Gastroenteritis and Colitis

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

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

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

4 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

5 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.

6 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

7 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

8

9 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

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

11 Volume Status

12 Volume Status

13 Volume Status

14 Volume Status

15 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

16 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

17 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

18 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

19 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

20 Reduced-Osmolarity Oral Rehydration Solution STANDARD REDUCED meq or mmol/l meq or mmol/l Glucose Sodium Chloride Potassium Citrate Osmolarity

21 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

22 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

23 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

24 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: AST AST ALT ALT

25 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)

26 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)

27 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

28 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.)

29 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

30 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)

31 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.

32 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

33 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

34 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

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

36 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.

37 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

38 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

39 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

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

41 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

42 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

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

44 References Bern C. Diarrhoeal Diseases. In: Murray CJL, Lopez AD, Mathers CD, eds. The Global Epidemiology of Infectious Diseases. Geneva, Switzerland: World Health Organization; Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32(3): Jones TF, Bulens SN, Gettner S, et al. Use of stool collection kits delivered to patients can improve confirmation of etiology in foodborne disease outbreaks. Clin Infect Dis 2004;39(10): DuPont HL. Clinical practice. Bacterial diarrhea. N Engl J Med 2009;361(16): Beaugerie L, Petit JC. Microbial-gut interactions in health and disease. Antibiotic-associated diarrhoea. Best Pract Res Clin Gastroenterol 2004;18(2): Gorkiewicz G. Nosocomial and antibiotic-associated diarrhoea caused by organisms other than Clostridium difficile. Int J Antimicrob Agents 2009;33 Suppl 1:S Alfredson DA, Korolik V. Antibiotic resistance and resistance mechanisms in Campylobacter jejuni and Campylobacter coli. FEMS Microbiol Lett 2007;277(2): Nachamkin I, Ung H, Li M. Increasing fluoroquinolone resistance in Campylobacter jejuni, Pennsylvania, USA, Emerg Infect Dis 2002;8(12): Su LH, Chiu CH. Salmonella: clinical importance and evolution of nomenclature. Chang Gung Med J 2007;30(3): WHO Global Salmonella Survey, WHO Press, World Health Organization, (Accessed Sept 4, 2009, at

45 Helms M, Simonsen J, Molbak K. Quinolone resistance is associated with increased risk of invasive illness or death during infection with Salmonella serotype Typhimurium. J Infect Dis 2004;190(9): Molbak K. Human health consequences of antimicrobial drug-resistant Salmonella and other foodborne pathogens. Clin Infect Dis 2005;41(11): Varma JK, Molbak K, Barrett TJ, et al. Antimicrobial-resistant nontyphoidal Salmonella is associated with excess bloodstream infections and hospitalizations. J Infect Dis 2005;191(4): Niyogi SK. Shigellosis. J Microbiol 2005;43(2): Khan WA, Seas C, Dhar U, Salam MA, Bennish ML. Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial. Ann Intern Med 1997;126(9): Taylor DN, McKenzie R, Durbin A, et al. Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge. Clin Infect Dis 2006;42(9): Gyles CL. Shiga toxin-producing Escherichia coli: an overview. J Anim Sci 2007;85(13 Suppl):E Talan D, Moran GJ, Newdow M, et al. Etiology of bloody diarrhea among patients presenting to United States emergency departments: prevalence of Escherichia coli O157:H7 and other enteropathogens. Clin Infect Dis 2001;32(4): Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005;365(9464): Iijima K, Kamioka I, Nozu K. Management of diarrhea-associated hemolytic uremic syndrome in children. Clin Exp Nephrol 2008;12(1):16-9. Dundas S, Todd WT, Stewart AI, Murdoch PS, Chaudhuri AK, Hutchinson SJ. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis 2001;33(7): Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342(26):

46 Ochoa TJ, Chen J, Walker CM, Gonzales E, Cleary TG. Rifaximin does not induce toxin production or phage-mediated lysis of Shiga toxin-producing Escherichia coli. Antimicrob Agents Chemother 2007;51(8): McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353(23): Sailhamer EA, Carson K, Chang Y, et al. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg 2009;144(5):433-9; discussion Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007;245(2): Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J, Jr. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16(8): Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45(3): Surawicz CM. Treatment of recurrent Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol 2004;1(1):32-8. Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol 2000;95(11): Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 2003;36(5): Beaugerie L, Metz M, Barbut F, et al. Klebsiella oxytoca as an agent of antibiotic-associated hemorrhagic colitis. Clin Gastroenterol Hepatol 2003;1(5): McGee S, Abernethy WB, 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA 1999;281(11): Gill CJ, Lau J, Gorbach SL, Hamer DH. Diagnostic accuracy of stool assays for inflammatory bacterial gastroenteritis in developed and resource-poor countries. Clin Infect Dis 2003;37(3):

47 Silletti RP, Lee G, Ailey E. Role of stool screening tests in diagnosis of inflammatory bacterial enteritis and in selection of specimens likely to yield invasive enteric pathogens. J Clin Microbiol 1996;34(5): WHO/UNICEF. Clinical Management of Acute Diarrhoea. WHO/UNICEF Joint Statement Gadewar S, Fasano A. Current concepts in the evaluation, diagnosis and management of acute infectious diarrhea. Curr Opin Pharmacol 2005;5(6): Riddle MS, Arnold S, Tribble DR. Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in traveler's diarrhea: a systematic review and meta-analysis. Clin Infect Dis 2008;47(8): Loftus CG, Pardi DS. Gastrointestinal Infections, Clostridium difficile-associated Disease, and Diverticular Disease. In: Mayo Clinic Gastroenterology and Hepatology Board Review. Eds: Hauser, SC, Pardi DS, Pterucha JJ. Mayo Clinic Scientific Press, Rochester, MN Pg , Wilhelmi I, Roman E, Sanchez-Fauquier A. Viruses causing gastroenteritis. Clin Microbiol Infect 2003;9(4): Clark B, McKendrick M. A review of viral gastroenteritis. Curr Opin Infect Dis 2004;17(5):461-9 Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(RR-2):1-25.

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