Infectious Gastroenteritis and Colitis

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
Lower abdominal pain
Large volume stools
Small volume stools
Watery stools
May be bloody
Malabsorption & dehydration
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 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












– Parasites




E. histolytica
T. trichiura
Balantidium coli
Blastocystis hominis
Salmonella
Shigella
Campylobacter
STEC or EHEC, EIEC
C. difficile
Yersinia
Non-cholera vibrios
Plesiomonas & Aeromonas
Tuberculosis
Klebsiella oxytoca
C. perfringens
S. aureus
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
31
4.0
1.1
AST 44
ALT 32
10.2
110
19.5
139
45
3.6
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
– 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.)
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%)
– 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)
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
– 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
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)
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:
– 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, MACG
Professor of Medicine
University of Washington
Chief, Gastroenterology
Harborview Medical Center
References
Bern C. Diarrhoeal Diseases. In: Murray CJL, Lopez AD, Mathers CD, eds. The Global
Epidemiology of Infectious Diseases. Geneva, Switzerland: World Health Organization; 2004.
Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious
diarrhea. Clin Infect Dis 2001;32(3):331-51.
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):1454-9.
DuPont HL. Clinical practice. Bacterial diarrhea. N Engl J Med 2009;361(16):1560-9.
Beaugerie L, Petit JC. Microbial-gut interactions in health and disease. Antibiotic-associated
diarrhoea. Best Pract Res Clin Gastroenterol 2004;18(2):337-52.
Gorkiewicz G. Nosocomial and antibiotic-associated diarrhoea caused by organisms other than
Clostridium difficile. Int J Antimicrob Agents 2009;33 Suppl 1:S37-41.
Alfredson DA, Korolik V. Antibiotic resistance and resistance mechanisms in Campylobacter jejuni
and Campylobacter coli. FEMS Microbiol Lett 2007;277(2):123-32.
Nachamkin I, Ung H, Li M. Increasing fluoroquinolone resistance in Campylobacter jejuni,
Pennsylvania, USA,1982-2001. Emerg Infect Dis 2002;8(12):1501-3.
Su LH, Chiu CH. Salmonella: clinical importance and evolution of nomenclature. Chang Gung Med
J 2007;30(3):210-9.
WHO Global Salmonella Survey, 2000-2005. WHO Press, World Health Organization, 2006.
(Accessed Sept 4, 2009, at http://www.who.int/salmsurv/links/GSSProgressReport2005.pdf.)
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):1652-4.
Molbak K. Human health consequences of antimicrobial drug-resistant Salmonella and other
foodborne pathogens. Clin Infect Dis 2005;41(11):1613-20.
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):554-61.
Niyogi SK. Shigellosis. J Microbiol 2005;43(2):133-43.
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):697-703.
Taylor DN, McKenzie R, Durbin A, et al. Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis
after experimental challenge. Clin Infect Dis 2006;42(9):1283-8.
Gyles CL. Shiga toxin-producing Escherichia coli: an overview. J Anim Sci 2007;85(13 Suppl):E45-62.
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):573-80.
Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic
syndrome. Lancet 2005;365(9464):1073-86.
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):923-31.
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):1930-6.
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):2837-41.
McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium
difficile. N Engl J Med 2005;353(23):2433-41.
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 9-40.
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):267-72.
Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J, Jr. Clostridium difficile-associated diarrhea
and colitis. Infect Control Hosp Epidemiol 1995;16(8):459-77.
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):302-7.
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):3283-5.
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):580-5.
Beaugerie L, Metz M, Barbut F, et al. Klebsiella oxytoca as an agent of antibiotic-associated
hemorrhagic colitis. Clin Gastroenterol Hepatol 2003;1(5):370-6.
McGee S, Abernethy WB, 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic?
JAMA 1999;281(11):1022-9.
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):365-75.
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):1161-5.
WHO/UNICEF. Clinical Management of Acute Diarrhoea. WHO/UNICEF Joint Statement 2004.
Gadewar S, Fasano A. Current concepts in the evaluation, diagnosis and management of acute
infectious diarrhea. Curr Opin Pharmacol 2005;5(6):559-65.
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):1007-14.
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. 2008. Pg. 223239, 271-279
Wilhelmi I, Roman E, Sanchez-Fauquier A. Viruses causing gastroenteritis. Clin Microbiol Infect
2003;9(4):247-62.
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.