Clinical Correlation:Enteric InfectionsBacterial Diarrhea

Chris E. Forsmark, M.D.Division of Gastroenterology, Hepatology,

and Nutrition

Infectious Diarrhea

• 3-5 billion episodes yearly• Major cause of worldwide morbidity and

mortality• 5 million deaths yearly, 80% < 1 year of age• Major cause of work/school absenteeism• Major economic burden, especially in

developing countries• Bacteria cause 5.2 million cases of diarrhea

in US yearly (80% foodborne)

Organisms

• Bacteria– E. Coli, Salmonella, Shigella, Campylobacter,

Vibrio, Yersinia, Clostridium difficle, S. aureus, B. cereus, C. botulinum

• Viruses– Norovirus, Rotavirus, CMV

• Parasites– Giardia, Amoeba, Ascaris, etc

These organisms cause diarrhea through a wide variety of mechanisms

Pathophysiology– Osmotic– Secretory– Exudation– Abnormal motility

Osmotic Diarrhea

• Interferes with absorption of water• Solutes are ingested (fasting stops diarrhea)– Magnesium sulfate or citrate or magnesium

containing antacids– Sorbitol– Malabsorption of food

• Lactase deficiency• Celiac sprue• Variety of infectious organisms (particularly viruses)

Definition: Increased amounts of poorly absorbed, osmotically active solutes in gut lumen

Secretory Diarrhea

• Excess secretion of electrolytes and water across mucosal surface

• Usually coupled with inhibition of absorption• Clinical features– stools very watery– stool volume large– fasting does not stop diarrhea

Secretory Diarrhea

Bacterial or viral enterotoxins• Vibrio cholerae• Noncholeraic vibrios• Enterotoxigenic E. coli• B. cereus• S. aureus• Others: Rotavirus, Norovirus

Non-infectious causes

Exudative Diarrhea• Intestinal or colonic mucosa inflamed and

ulcerated– Leakage of fluid, blood, pus– Impairment of absorption– Increased secretion (prostaglandins)

• The extent and location of bowel involved determines– Severity of diarrhea– Systemic signs and symptoms (abdominal pain,

fever, leukocytosis, etc)– Tenesmus, urgency

Exudative Diarrhea

• Infectious, invasive organisms– Shigella, Campylobacter, Yersinia, E.

histolytica, EIEC, C diff– CMV

• Idiopathic inflammatory bowel disease– Crohns disease– Ulcerative Colitis

• Ischemia

Invasive organisms produce leukocytes and blood in stool

A laboratory equivalent of this is the presence of lactoferrin in a sample of stool

Abnormal Motility

• Increased colonic motility– Irritable bowel syndrome

• Increased small bowel motility– Hyperthyroidism, post-operative dumping

• Decreased small bowel motility– Scleroderma, with bacterial overgrowth

• Anal sphincter dysfunction– Incontinence

Diarrhea• Non-inflammatory– Watery diarrhea, no blood or mucus or pus in stool, no

fever or systemic signs– Secretory or osmotic mechanism– Dehydration may occur– Generally self-limited and more benign– Therapy generally supportive

• Inflammatory– Frequent lower volume stool, mucoid, bloody, or

purulent. Often with fever or systemic signs, tenesmus, urgency

– Exudative mechanism– Dehydration rare– Less benign

Common syndromes of infectious diarrhea

• Food poisoning• Acute watery diarrhea– Travelers diarrhea– Epidemics

• Acute bloody diarrhea– Dysentery

Special circumstances

• Outbreaks/food poisoning• Overseas travel• Immunocompromised host• Raw seafood ingestion• Antibiotic usage

History

• Onset and duration of diarrhea• Timing of exposure to potential pathogens– Travel, ingestion history, environment, recent

medications (antibiotics), age

• Character of stool– Volume, presence of blood, mucus, or pus

• Associated symptoms and signs– Abdominal pain, fever, vomiting, dehydration

Physical examination

• Vital signs: Fever, tachycardia• Abdominal tenderness or pain• Signs of dehydration• Blood, mucus, or pus in stool

E. coliType Clinical Features Complications

ETEC Watery diarrhea, travelers diarrhea

rare

EHEC

(Shiga toxin 1 and 2)

Bloody diarrhea Hemolytic uremic syndrome, TTP (mostly 0157:H7)

EIEC bloody diarrhea, dysentery rare

EAEC Watery diarrhea or bloody diarrhea, mainly in children

May be protracted

Nontyphoidal Salmonella

• Salmonella typhimurium and enteritidis• Clinical syndromes– Gastroenteritis (non-inflammatory) and colitis

(inflammatory)– Bacteremia and endocarditis– Enteric fever (typhi and paratyphi)– Localized tissue infection– Carrier state (> 1 year)

• Food-borne illness (poultry, meat, eggs)

Shigella

• dysenteriae, flexneri, boydii, sonnei• Usually bloody diarrhea• May be complicated by reactive arthritis and

rarely HUS• Very infectious ( ~100 organisms cause

disease)

Campylobacter

• Mainly C. jejuni• Transmission from infected animals or food

products, fresh or salt water• Usually bloody diarrhea or dysentery• May be complicated by Guillain-Barré and

IPSID

Vibrio

• Cholera• Non choleriac• Enterotoxin elaborated causes severe watery

diarrhea• Complications common due to dehydration

Classic Syndromes: Acute food poisoning

• Similar illness in 2 or more persons• Epidemiologic evidence of common food source• Onset of symptoms typically within 6 hours of

ingestion• Nausea and vomiting prominent• Preformed toxin of S. aureus or B. cereus • Longer incubation periods for C. perfringens

Classic Syndromes: Travelers Diarrhea

• Attack rates of as high as 25%

• 90% brief and self-limited

• Persistent diarrhea in 1-2%

• Depends on destination, eating habits, length of stay

Pathogen %

ETEC 40

EAEC 15

C. jejuni 10

Shigella 10

EHEC or EIEC

<5

Salmonella < 5

Vibrio < 5

Food-borne illness

Agent %

Norovirus 45

C. perfringens 12

Salmonella 11

S. aureus 4

EHEC (0157) 4

C. jejuni 4

B. cereus 2

Shellfish-borne

%

Norovirus 52

Vibrio 37

Salmonella <1

Other 10

Nosocomial diarrhea

• Clostridium difficle• Increasing worldwide due

to hypervirulent strain (North American Pulsefield type 1)

• High fluoroquinolone resistance

• Less responsive to usual therapy (metronidazole)

• Higher complication rate

Evaluation of diarrhea• How long has the diarrhea been present?• Was it acquired in a particular environment?– Hospital– Recent antibiotic use– While traveling– Day care, cruise ship, picnic, etc– Exposure to sick persons

• What are the characteristics of the diarrhea– Is there blood, mucus, or pus in the stool– Is it high volume or low volume– Is there associated tenesmus or urgency

• What are the associated symptoms?– Fever, abdominal pain, vomiting, dehydration

Is evaluation required in every patient?

• No• Evaluate those with high fever, systemic

illness, tenesmus, blood/pus in stool, dehydration, immunocompromised, prolonged course

• Remainder can often be managed without specific diagnosis with rehydration and anti-peristaltic agents

Evaluation of Infectious Diarrhea

• Stool studies– fecal leukocytes or lactoferrin, RBC/blood– Bacterial culture• Include C. difficle toxin assay• May need to request EHEC screen

• Endoscopic evaluation may be useful in some– especially for bloody diarrhea or chronic

diarrhea

Fecal PMNs

• Common in Shigella, Campylobacter, EIEC, C. diff

• Less common in Salmonella, Yersinia, ETEC, EAEC

• Now largely replaced with fecal lactoferrin

Treatment of Diarrhea

• Treatment of specific etiology• Non-specific treatment– hydration– Absorptions (Kaopectate®)– Bismuth – Antiperistaltics/opiate derivatives– Fiber supplementation

Oral rehydration solutions

Components WHO Ricelyte Pedialyte

Na (mEq/L) 90 50 45

K (mEq/L) 20 25 20

Cl (mEq/L) 80 45 35

Citrate (mEq/L) 30 34 30

Glucose (g/L) 20 30 25

Why not treat everyone with bacterial diarrhea?

• Some have no effective specific treatment• Treatment may not change disease duration

or severity• Treatment may predispose to carrier state• Treatment may produce complications (HUS,

antibiotic resistance, C. difficle, toxic megacolon)

Who should be treated?Antibiotics indicated Antibiotics indicated if

•Severely ill

•immunocompromised

Antibiotics not indicated

Shigella Campylobacter EHEC

ETEC Yersinia viruses

V. cholera EAEC Food poisoning

C. diff Salmonella

Antibiotic choice• E. coli– Quinolone

• Shigella– Quinolone or TMP-SMX

• Vibrio cholera– Tetracycline or quinolone

• Salmonella– Quinolone or TMP-SMX

• Campylobacter– Erythromycin or quinolone

• Yersinia– tetracycline, TMP-SMX, or quinolone