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. 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).

Transmission

Diarrheagenic pathotypes can be passed in the feces of humans and other animals. Transmission occurs through the fecal-oral route, primarily via contaminated food or water and also through person-to-person contact and contact with animals or their environment. People 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.

Epidemiology

Travel to less-developed countries is associated with higher risk for travelers’ diarrhea, including some types of E. coli infection. ETEC is the most common pathotype that causes diarrhea among travelers returning from most regions. Travel-associated infections caused by non-STEC diarrheagenic E. coli are likely underrecognized because most clinical laboratories do not use methods that can detect them. 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. Additional information about travelers’ diarrhea is available in Chapter 2, Travelers’ Diarrhea.

Clinical Presentation

Where information is available, non-STEC diarrheagenic E. coli infections have an incubation period ranging from 9 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 3-1).

Table 3-1. Mechanism of pathogenesis and typical clinical syndrome of Escherichia coli pathotypes
PathotypeMechanism of PathogenesisTypical Clinical Syndrome
ETECSmall bowel adherence; heat-stable or heat-labile enterotoxin productionAcute watery diarrhea, afebrile, occasionally severe
EAECSmall and large bowel adherence mediated via various adhesions and accessory proteins; enterotoxin and cytotoxin productionWatery diarrhea with mucous, occasionally bloody; can cause prolonged or persistent diarrhea in children
EPECSmall bowel adherence and epithelial cell effacement mediated by intiminSevere acute watery diarrhea; may be persistent; common cause of infant diarrhea in developing countries
EIECMucosal invasion and inflammation of large bowelWatery diarrhea that may progress to bloody diarrhea (dysenterylike syndrome), fever
DAECDiffuse adherence to epithelial cellsWatery diarrhea but pathogenicity not conclusively demonstrated
STECLarge bowel adherence mediated via intimin; Shiga toxin 1, Shiga toxin 2 productionWatery 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 ≈6% of STEC O157 and ≈1% of non-O157 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 .

Diagnosis

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 use tests that can detect diarrheagenic E. coli other than STEC, although recently approved nucleic acid amplification tests that can detect ETEC are now available in some clinical laboratories. Testing for non-STEC pathotypes is typically done at public health laboratories and only when an outbreak of diarrheal illness of unknown origin is being investigated. In this situation, isolates may be submitted via state health departments to CDC for testing. These tests typically involve PCR testing or whole genome sequence analysis for the specific virulence genes of ETEC, EPEC, EAEC, EIEC, and DAEC.

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 non-O157 STEC with a test that detects Shiga toxins (or the genes that encode them). For more information, see www.cdc.gov/mmwr/preview/mmwrhtml/rr5812a1.htm. All presumptive E. coli O157 isolates and Shiga toxin–positive specimens should be sent to a public health laboratory for further characterization. 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.

Treatment

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 3-1) should be aware that administering antimicrobial agents may increase the risk of HUS. Resistance to antibiotics is increasing worldwide. The decision to use an antibiotic should be carefully weighed 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, HUS, and neurologic complications. (See Chapter 2, Travelers’ Diarrhea and Chapter 7, Traveling Safely with Infants & Children for information about managing travelers’ diarrhea in children.)

Prevention

There is no vaccine 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 be cognizant of possible infections among returning travelers.

CDC website: www.cdc.gov/ecoli

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Authors

Ciara E. O’Reilly, Martha Iwamoto, Patricia M. Griffin