Author(s): Jennifer Collins, Danielle Tack, Talia Pindyck, Patricia  Griffin

Infectious Agent

Escherichia coli are gram-negative bacteria that inhabit the gastrointestinal tract. Most types do not cause illness, but 5 pathotypes are associated with diarrhea: enterotoxigenic E. coli (ETEC), Shiga toxin–producing E. coli (STEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), and enteroinvasive E. coli (EIEC). In addition, diffusely adherent E. coli (DAEC) might also be associated with diarrhea. Pathotypes that are common causes of urinary tract infections, bloodstream infections, and meningitis are not covered here.

E. coli serotypes are determined by surface antigens (O and H), and specific serotypes tend to cluster within specific pathotypes. Pathotype determination typically is based on testing for virulence genes. Some E. coli have virulence genes of >1 pathotype; for example, the O104:H4 strain that caused a 2011 outbreak in Germany produced Shiga toxin and had adherence properties typical of EAEC.

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

Transmission

Diarrheagenic E. coli pathotypes can be passed in the feces of humans and other animals. Transmission occurs through the fecal–oral route, via consumption of contaminated food or water, and 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.

Epidemiology

The 2010 World Health Organization (WHO) Global Burden of Foodborne Diseases report estimated ≈111 million illnesses and ≈63,000 deaths caused by diarrheagenic E. coli globally each year. Rates of infection vary by region, and certain types of diarrheagenic E. coli infections, mainly ETEC, are associated with travel to low- and middle-income countries. The incidence of travel-associated diarrhea caused by E. coli is likely underestimated because many travelers do not seek medical care or have stool testing performed, particularly if diarrhea is non-bloody, as commonly occurs with ETEC infection. Moreover, many clinical laboratories do not use methods that can detect diarrheagenic E. coli other than STEC in stool samples.

Risk for travelers’ diarrhea can be divided into 3 levels, according to the destination country. Low-risk countries include Australia, Canada, Greenland, Japan, New Zealand, the United States, and countries in northern and western Europe. Intermediate-risk countries include Argentina, Brazil, Chile, Morocco, Portugal, South Africa, Thailand (in Bangkok, Chiang Mai, and Phuket; risk to travelers going to rural areas is likely greater), Uruguay, and most countries in the Caribbean, eastern Europe, and the Middle East. High-risk countries include Afghanistan, Burma (Myanmar), the Indian subcontinent, Indonesia, Iran, Malaysia, Mexico, Papua New Guinea, most countries in Africa, and countries in Central America and northern South America, including Bolivia and Paraguay.

STEC infections are most commonly reported in industrialized countries, and ≈85% of STEC infections among international travelers are caused by non-O157 serotypes. Additional information about travelers’ diarrhea is available in Sec. 2, Ch. 6, Travelers’ Diarrhea.

Clinical Presentation

Diarrheagenic E. coli infections, other than STEC, have incubation periods ranging from 8 hours to 3 days. The median incubation period of STEC infection is 3–4 days, with a range of 1–10 days. Clinical manifestations of diarrheagenic E. coli vary by pathotype (see Table 5-02).
Table 5-02 Mechanism of pathogenesis & typical clinical syndrome of Escherichia coli pathotypes

Diagnosis

Diagnostic testing is not usually recommended for uncomplicated travelers’ diarrhea unless treatment is indicated. Until recently, diarrheagenic E. coli other than STEC could not be distinguished from non-pathogenic E. coli in stool using routine tests in clinical laboratories. Commercial molecular tests have increasingly become available and can identify ETEC, EPEC, EAEC, and EIEC through detection of virulence genes.

Consider several caveats when interpreting results of such tests. The combination of virulence genes that confer pathogenicity has not been determined for all pathotypes, and E. coli sometimes have virulence genes from >1 pathotype due to transfer of mobile genetic elements. Some studies have identified some genes, including the eae gene used to diagnose EPEC, at a similar frequency in stools from healthy people as from those with acute diarrhea. Identification of 2 virulence genes in a specimen does not mean they are carried by the same organism. Finally, molecular tests detect genetic material, which does not always correspond to the presence of viable organisms.

Using PCR or whole-genome sequence analysis to facilitate recognition of specific E. coli pathotypes, state public health and Centers for Disease Control and Prevention laboratories can assist in outbreak investigations. When STEC infection is suspected, stool samples should be cultured for E. coli O157 and simultaneously tested for Shiga toxins or the genes that encode them. See more information. Send all presumptive E. coli O157 isolates and Shiga toxin–positive specimens 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 further transmission.

Treatment

Maintenance of hydration and electrolyte balance with oral rehydration is important, especially in patients with vomiting or profuse diarrhea. Travelers with mild non-bloody diarrhea can use loperamide to decrease the frequency of loose stools. Travelers with moderate illness can consider self-treatment with an antibiotic, and those with bloody diarrhea or severe illness (that keeps them confined to their room) should generally receive antibiotic therapy. Travelers can use loperamide as an adjunctive therapy to antibiotics taken for moderate or severe travelers’ diarrhea.

Azithromycin is preferred for bloody diarrhea or severe illness and is an option for moderate non-bloody diarrhea. Fluoroquinolones (e.g., ciprofloxacin) can be effective, but resistant strains are increasing in frequency, particularly in Asia; other agents are also preferred because fluoroquinolones have been associated with adverse effects, including tendinopathies, QT interval prolongation (a cardiac conduction abnormality), and Clostridioides difficile enterocolitis.

If treatment with azithromycin or a fluoroquinolone does not improve the condition within 24 hours, travelers should continue the antibiotic for no longer than 3 days. A 3-day course of rifaximin is effective for some non-bloody diarrheal illnesses. Administering certain antimicrobial agents to patients whose clinical syndrome suggests STEC infection could increase their risk of developing HUS (Table 5-02). Studies of children with STEC O157 infection have shown that early use of intravenous fluids (within the first 4 days of diarrhea onset) might decrease the risk of oligoanuric renal failure.

Antimicrobial-resistant E. coli are increasing worldwide. Carefully weigh the decision to use an antibiotic against the severity of illness; the possibility that the pathogen is resistant; and the risk for adverse reactions (e.g., HUS, rash, other manifestations of allergy), antibiotic-associated colitis, and vaginal yeast infection. Some studies suggest that loperamide combined with antibiotics can be used safely in many patients. Due to a potential risk for complications, including toxic megacolon and HUS, avoid treating bloody diarrhea or STEC infection solely with antimotility drugs.

Prevention

No vaccine is available for E. coli infection. Although bismuth subsalicylate and certain antimicrobial agents (e.g., fluoroquinolones, rifaximin) can prevent E. coli diarrhea, chemoprophylaxis is not recommended for most travelers. Furthermore, antimicrobial drug use can adversely affect the intestinal microbiota and increase susceptibility to gut infections.

Remind travelers of the importance of adhering to food and water precautions (see Sec. 2, Ch. 8, Food & Water Precautions), and instruct travelers about the importance of handwashing. Because soap and water might not be readily available, travelers should consider taking hand sanitizer with ≥60% alcohol with them when they travel.

CDC website: E. coli