Escherichia Coli, Diarrheagenic

Infectious Agent

Escherichia coli are gram-negative bacteria that inhabit the gastrointestinal tract. Most strains do not cause illness. Pathogenic E. coli are categorized into pathotypes on the basis of their virulence genes. Six pathotypes are associated with diarrhea (diarrheagenic): enterotoxigenic E. coli (ETEC), Shiga toxin–producing E. coli (STEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), and possibly diffusely adherent E. coli (DAEC). Other pathotypes that are common causes of urinary tract infections, bloodstream infections, and meningitis are not covered here. Serotypes of E. coli are determined by surface antigens (O and H), and specific serotypes tend to cluster within specific pathotypes. Some E. coli have virulence factors of more than 1 pathotype, and new strains of E. coli continue to be recognized as causes of foodborne disease. An example is the O104:H4 strain that caused an outbreak in Germany in 2011; it produced Shiga toxin and had adherence properties typical of EAEC.

STEC are also called verotoxigenic E. coli (VTEC), and the term enterohemorrhagic E. coli (EHEC) is commonly used to specify STEC strains capable of causing human illness, especially bloody diarrhea and hemolytic uremic syndrome (HUS).


Diarrheagenic pathotypes can be passed in the feces of humans and other animals. Transmission occurs through the fecal–oral route, primarily via consumption of contaminated food or water, and also through person-to-person contact, contact with animals or their environment, and swimming in untreated water. Humans constitute the main reservoir for non-STEC pathotypes that cause diarrhea in humans. The intestinal tracts of animals, especially cattle and other ruminants, are the primary reservoirs of STEC.


Travel to less-developed countries is associated with a higher risk for travelers’ diarrhea, including some types of E. coli infection. Travel-associated infections caused by E. coli are likely underrecognized because illness may occur during travel, health care is often not sought or illness is treated empirically, and most clinical laboratories do not use methods that can detect non-STEC diarrheagenic E. coli . The WHO Global Burden of Foodborne Diseases report estimates that >300 million illnesses and nearly 200,000 deaths are caused by diarrheagenic E. coli globally each year. Rates of infection vary by region. ETEC is the most common pathotype that causes diarrhea among travelers returning from most regions. Risk of non-STEC diarrheagenic E. coli infections (primarily ETEC) can be divided into 3 grades, according to the destination country:

  • Low-risk countries include the United States, Canada, Australia, New Zealand, Japan, and countries in Northern and Western Europe.
  • Intermediate-risk countries include those in Eastern Europe, South Africa, and some of the Caribbean islands.
  • High-risk areas include most of Asia, the Middle East, Africa, Mexico, and Central and South America.

STEC infections are more commonly reported in industrialized countries than in less-developed countries. Among international travelers, about 75% of STEC infections are caused by non-O157 serotypes. Additional information about travelers’ diarrhea is available in Chapter 2, Travelers’ Diarrhea.

Clinical Presentation

Non-STEC diarrheagenic E. coli infections have an incubation period ranging from 8 hours to 3 days. The median incubation period of STEC infections is 3–4 days, with a range of 1–10 days. The clinical manifestations of diarrheagenic E. coli vary by pathotype (Table 4-1).


Many patients with travel-associated E. coli infections, especially those with nonbloody diarrhea, as commonly occurs with ETEC infection, are likely to be managed symptomatically and are unlikely to have the diagnosis confirmed by a laboratory. Most US clinical laboratories do not routinely use tests that can detect diarrheagenic E. coli other than STEC. Recently approved nucleic acid amplification tests that detect genes encoding putative virulence factors associated with non-STEC E. coli pathotypes (ETEC, EPEC, EAEC, EIEC) are now available in some clinical laboratories. However, the combination of virulence factors necessary for an E. coli strain to be a pathogen has not been determined for all pathotypes. For example, one PCR-based test relies on the eae gene that encodes the adhesion factor intimin to produce an EPEC result. However, many case-control studies have detected this gene with similar frequency in E. coli isolated from healthy people as from those with acute diarrhea. Therefore, EPEC might not be the etiology of illness for a person with diarrhea and a PCR-based EPEC result. The state public health and CDC laboratories can assist in the investigation of outbreaks for which an etiology has not been identified by testing for non-STEC E. coli pathotypes using PCR or whole genome sequence analysis; this is one way particular E. coli strains are recognized as pathogens.

When a decision is made to identify a cause of an acute diarrheal illness, in addition to routine culture for Salmonella, Shigella , and Campylobacter , the stool sample should be cultured for E. coli O157:H7 and simultaneously assayed for Shiga toxin with a test that detects the toxins or the genes that encode them. For more information, see All presumptive E. coli O157 isolates and Shiga toxin–positive specimens should be sent to a public health laboratory for further characterization and for outbreak detection. Rapid, accurate diagnosis of STEC infection is important, because early clinical management decisions can affect patient outcomes, and early detection can help prevent secondary spread.


Patients with profuse diarrhea or vomiting should be rehydrated. Evidence from studies of children with STEC O157 infection indicates that early use of intravenous fluids (within the first 4 days of diarrhea onset) may decrease the risk of oligoanuric renal failure. Antibiotics to treat non-STEC diarrheagenic E. coli include fluoroquinolones such as ciprofloxacin, macrolides such as azithromycin, and rifaximin. Clinicians treating a patient whose clinical syndrome suggests STEC infection (Table 4-1) should be aware that administering certain antimicrobial agents may increase the risk of HUS. Resistance to antibiotics is increasing worldwide. The decision to use an antibiotic should be weighed carefully against the severity of illness, the possibility that the pathogen is resistant, and the risk of adverse reactions such as rash, antibiotic-associated colitis, and vaginal yeast infection. Antimotility agents should be avoided in patients with bloody diarrhea and patients with STEC infection, because these agents may increase the risk of complications, including toxic megacolon and HUS. (See Chapter 2, Travelers’ Diarrhea and Chapter 7, Traveling Safely with Infants & Children for information about managing travelers’ diarrhea in children.)

Table 4-1. Mechanism of pathogenesis and typical clinical syndrome of Escherichia coli pathotypes


Mechanism of Pathogenesis

Incubation Period


of Illness

Typical Clinical Syndrome


Small bowel adherence via various adhesions that confer host specificity; heat-stable or heat-labile enterotoxin production

10–72 hours

1–5 days

Acute watery diarrhea, afebrile, occasionally severe


Small and large bowel adherence mediated via various adhesions and accessory proteins; enterotoxin and cytotoxin production

8–48 hours

3–14 days; persistent diarrhea (>14 days) has been reported

Watery diarrhea with mucous, occasionally bloody; can cause prolonged or persistent diarrhea in children


Small bowel adherence and epithelial cell effacement mediated by intimin

9–12 hours

12 days

Severe acute watery diarrhea; may be persistent; common cause of infant diarrhea in developing countries


Mucosal invasion and inflammation of large bowel

10–18 hours

4–7 days

Watery diarrhea that may progress to bloody diarrhea (dysentery-like syndrome), fever


Diffuse adherence to epithelial cells



Watery diarrhea but pathogenicity not conclusively demonstrated


Large bowel adherence mediated via intimin (or less commonly by other adhesions); Shiga toxin 1, Shiga toxin 2 production; Shiga toxin production is linked to induction of the bacteriophages carrying the Shiga toxin genes; some antibiotics induce these bacteriophages

1–10 days (usually 3–4 days)

Typically 5–7 days; persistent diarrhea (>14 days) has been reported

Watery diarrhea that progresses (often for STEC O157, less often for non-O157) to bloody diarrhea in 1–3 days; abdominal cramps and tenderness; if fever present, low-grade; hemolytic uremic syndrome complicates approximately 6% of diagnosed STEC O157 infections (15% among children aged <5 years) and 1% of non-O157 STEC infections

Abbreviations: ETEC, enterotoxigenic E. coli ; EAEC, enteroaggregative E. coli ; EPEC, enteropathogenic E. coli ; EIEC, enteroinvasive E. coli ; DAEC, diffusely adherent E. coli ; STEC, Shiga toxin–producing E. coli .


No vaccine is available for E. coli infection, nor are any medications recommended for prevention. Taking antibiotics can adversely affect the intestinal microbiota and increase susceptibility to gut infections. Food and water are primary sources of E. coli infection, so travelers should be reminded of the importance of adhering to food and water precautions (see Chapter 2, Food & Water Precautions). People who may be exposed to livestock, especially ruminants, should be instructed about the importance of handwashing in preventing infection. Because soap and water may not be readily available in at-risk areas, travelers should consider taking hand sanitizer that contains ≥60% alcohol. During E. coli outbreaks, clinicians should alert people traveling to affected areas and should be cognizant of possible infections among returning travelers.

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Alison Winstead, Jennifer C. Hunter, Patricia M. Griffin