Diarrheagenic E. coli

Escherichia coli (E. coli) is a gram-negative, rod-shaped flagellated bacterium. Although it is an essential component of the bacterial gut flora, the disease may be caused by direct intake of a pathogenic E. coli subtype (e.g., in contaminated food) or spreading of the intestinal bacteria to another organ (cystitis, pneumonia). Enterohemorrhagic E. coli (EHEC), for instance, can lead to severe colitis and hemolytic uremic syndrome (HUS), particularly in children and infants. In such cases, diarrhea should only be treated symptomatically, as antibiotics can lead to increased toxin secretions that exacerbate the course of the disease. Supportive therapy without antibiotic therapy is also recommended for infection involving other strains of E. coli (ETEC, EPEC, and EIEC), but antibiotics may be indicated in certain cases.

• Pathogen: Escherichia coli (E. coli) ^[1]
  • Gram-negative, rod-shaped, indole-positive, and flagellated
  • Various pathogenic strains of E. coli include:
    • Enterohemorrhagic E. coli (EHEC)
    • Enterotoxigenic E. coli (ETEC)
    • Enteropathogenic E. coli (EPEC)
    • Enteroinvasive E. coli (EIEC)
  • Some strains are an essential component of the bacterial gut flora and even have a protective effect against enteropathogens. ^[2]
• Transmission: fecal-oral ^[3]
  • Contaminated food (e.g., raw meat products, vegetables, fruits) and water
  • Person-to-person
• Diagnostic steps ^[4]
  • Culture and/or PCR from stool samples
  • Differential media (based on E.coli lactose fermenting properties)
    • MacConkey agar: pink colonies
    • Eosin-methylene blue agar: colonies with a metallic green sheen
• Differential diagnosis
  • Food poisoning
  • Bacterial gastroenteritis
  • Norovirus infection
  • Rotavirus infection
• General guidelines for treating E. coli infections ^[5][6]
  • Supportive therapy ^[7]
    • Rehydration and electrolyte replenishment (e.g., oral rehydration salts or solutions; IV fluids)
    • Clear liquids, easy-to-digest foods
    • The patient should return to a normal diet as soon as tolerated .
  • Antibiotic therapy for E. coli: Although some indications exist, antibiotic therapy is generally not recommended and is strongly contraindicated in EHEC.
    • Considered only in cases of severe and/or persistent diarrhea (see the individual sections below for specific indications)
    • First-line agents in adults: fluoroquinolones (e.g., ciprofloxacin, norfloxacin, levofloxacin, and moxifloxacin)
    • Alternative (drug of choice in children and pregnant women): azithromycin

Do not use antibiotics if EHEC is suspected.

• Pathogen: enterohemorrhagic E. coli (EHEC)
  • Produces Shiga-like toxin (verotoxin) that causes bloody diarrhea and, possibly, HUS
  • O157:H7 is the strain most commonly associated with HUS worldwide.
• Transmission: fecal-oral ; ^[8]
  • Contaminated food (associated with industrial food production in developed countries)
    • Raw beef and milk
    • Raw vegetables
  • Contact with contaminated stool
  • At-risk groups: infants/toddlers and the elderly
• Pathophysiology ^[9][10]
  • EHEC bacteria are infected by bacteriophages that integrate their genes into the bacteria's genome; these genes then code for toxins (verotoxin/Shiga toxin 1 and 2).
  • Adhesion to receptors of gut cells; → Shiga-like toxin secretion → cleavage of adenine from the rRNA → inactivation of the 60S subunit → protein synthesis inhibition → cell death → necrosis and inflammation of the GI mucosa → watery-bloody diarrhea with mucus (otherwise known as dysentery)
• Incubation period: 2–10 days
• Clinical features ^[11]
  • Bloody diarrhea, dehydration, and abdominal tenderness
  • Little to no fever ^[12]
  • See “Hemolytic uremic syndrome” for its specific symptoms (e.g., decreased urine output, petechiae, and neurologic manifestations).
• Diagnosis ^[13]
  • Stool samples should be tested for EHEC:
    • In all cases of community-acquired diarrhea
    • In possible HUS/TTP
  • Culture for O157:H7 on sorbitol MacConkey agar
  • Check for non-O157 EHEC by detection of Shiga toxins (via enzyme immunoassay) or Shiga toxin-encoding genes (via polymerase chain reaction)
• Treatment ^[14]
  • Monitor for possible development of HUS.
  • Avoid antiperistaltic agents (e.g., diphenoxylate/atropine) since they increase the risk of systemic complications.
  • Antibiotic therapy is contraindicated.
  • See “General guidelines for treating E. coli infections”.
• Complications: HUS (particularly in infants/toddlers )
• Obligation to report: EHEC infection and HUS infection are reportable in most US states.

EHEC leads to HUS.

• Epidemiology ^[15]
  • Enterotoxigenic E. coli (ETEC) is the most common pathogen causing traveler's diarrhea.
  • A major cause of diarrhea among children in developing countries
  • Very common while traveling in Asian, African, and Latin American countries
• Pathophysiology ^[16]
  • ETEC produces two types of enterotoxins:
    • Heat-labile enterotoxin (AB toxin; two-component protein, similar to cholera toxin): activation of adenylate cyclase → ↑ cAMP levels → ↑ chloride secretion → water efflux into the intestinal lumen → secretory diarrhea
    • Heat-stable enterotoxin: activation of guanylate cyclase → ↑ cGMP levels → ↓ NaCl reabsorption → water efflux into the intestinal lumen → secretory diarrhea
  • No invasion of the intestinal mucosa and no inflammation
• Clinical presentation: Symptoms last 3–4 days.
  • Watery diarrhea
  • Abdominal cramping
  • Nausea; , possibly vomiting
  • Fever
  • Decreased appetite
• Treatment ^[5][15]
  • Antibiotics may shorten the duration of symptoms.
  • Bismuth subsalicylate compounds may decrease the frequency of bowel movements.
  • See “General guidelines for treating E. coli infections”.
• Prevention ^[17]
  • Practice good food and water safety.
  • Prophylactic antibiotics are not recommended for most travelers.
  • Prophylaxis may be considered for pregnant women and immunocompromised patients.

ETEC causes Travelers' diarrhea.

• Pathogen: Enteropathogenic E. coli (EPEC) leads to infantile diarrhea.
• Epidemiology ^[18]
  • Adults are less susceptible to EPEC infection.
  • A common cause of diarrhea in children < 5 years old, especially in developing countries
  • After rotavirus infections, EPEC is one of the leading causes of death in children in developing countries.
• Pathophysiology ^[19]
  • EPEC blocks absorption by attaching to the apical surfaces of the intestinal epithelium, causing the villi to flatten.
  • No toxin production is involved.
• Clinical presentation ^[20]
  • 10–20 watery bowel movements per day for about 2 weeks
  • Vomiting
  • Low-grade fever
• Treatment ^[21]
  • In cases of persistent diarrhea (e.g., loose stools for > 2 weeks) antibiotics may be used.
  • See “General guidelines for treating E. coli infections”.

EPEC causes Pediatric diarrhea.

• Pathogen: enteroinvasive E. coli (EIEC)
• Pathophysiology: invasion of gut epithelium → inflammation and necrosis
• Clinical presentation
  • Watery to bloody diarrhea, possibly with mucus (dysentery)
  • Fever, chills, malaise
  • Abdominal cramps
  • Possibly vomiting
  • Symptoms similar to shigellosis
• Treatment: See “Antibiotic therapy for E. coli”.

EIEC Invades the Intestinal mucosa.

References:^[18]