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Escherichia Coli

Essentials of Diagnosis

  • Enteritis caused by E coli may be watery (any E coli subtype), mucoid [enteroaggregative E coli (EAggEC)], hemorrhagic [enterohemorrhagic E coli (EHEC)], or dysenteric [enteroinvasive E coli (EIEC)] and is associated with fever and abdominal pain.
  • Hemolytic uremic syndrome, caused by EHEC, consists of hemolytic anemia, uremia, and systemic symptomatology.
  • Risks for E coli-induced enteritis include ingestion of fecally contaminated food (EHEC, EIEC) or water [enterotoxigenic E coli (ETEC), EIEC, EAggEC, enteropathogenic E coli (EPEC), and diffusely adherent E coli (DAEC)], especially in endemic areas, or close contact with infected individuals (EIEC, EHEC).
  • E coli-induced enteritis is also indicated by microbiologic isolation and identification of enteric pathogens or molecular evidence of infection in the appropriate clinical setting.

General Considerations


E coli is the most common member of the Enterobacteriaceae to be isolated in the clinical microbiology laboratory. Most E coli isolates are either opportunistic or nosocomial pathogens (ie, causes of urinary tract or wound infections) or normal flora (ie, enteric contaminants of urine cultures or normal stool flora in stool cultures). There are, however, at least six diarrheagenic varieties of E coli. Some of these produce enteritis alone, whereas others produce enteritis-associated systemic disease that may be fatal. The six types of diarrheagenic E coli are the ETEC, EHEC, EIEC, and three distinct subtypes of enteroadherent E coli — the EPEC, EAggEC, and DAEC.

Escherichia Coli


The ETEC are spread by the fecal-oral route and are most common in developing countries that lack appropriate sanitation and drinking-water treatment facilities. Disease may occur at any time of the year, but incidence peaks in the warm, wet seasons that favor environmental bacterial replication. The most important mode of transmission is contaminated, improperly treated drinking water. Fruits and vegetables that are washed with contaminated water and not cooked before they are eaten also serve as vehicles of transmission. Person-to-person spread is uncommon.

In a normal host, exposure to ETEC leads to the development of mucosal immunity, presumably secondary to secretory immunoglobulin A (IgA) antibodies directed toward the fimbriae-associated colonization factor antigens (CFAs). In endemic areas, natural resistance is usually well developed in adults. These individuals serve as carriers and shed large numbers of toxigenic E coli into the environment. Disease occurs in those lacking mucosal immunity, principally neonates and travelers from nonendemic areas.


The EHEC are commensals and pathogens of live stock. Food, water, or unpasteurized beverages that are contaminated with animal feces are the principal modes of spread, but person-to-person transmission is also possible. EHEC commonly colonize cattle. Beef frequently becomes contaminated with bovine feces during the slaughter process. Ground beef that is contaminated is especially hazardous, because grinding distributes the bacteria through the meat. When hamburgers are made from contaminated beef and not cooked thoroughly, the bacteria are able to survive. The EHEC are more acid tolerant than many other bacterial enteric pathogens, with the possible exception of Shigella species, and relatively small inocula can survive gastric passage in humans and cause disease. Good cooking practices and food preparation hygiene can significantly reduce the likelihood of EHEC infections (see “Prevention” section).


The EIEC are spread by the fecal/oral route. Contaminated food and water are the usual vehicles of spread and food-borne outbreaks have occurred. Person-to-person transmission is possible but is uncommon. Compared with Shigella species, a higher infective dose of EIEC is required to cause disease. Infections by EIEC are thought to be rare, but this is unclear, because EIEC may be mistaken for Shigella species.

Enteroadherent E coli

Contaminated food, water, and fomites serve as vehicles for the fecal/oral transmission of the enteroadherent E coli. Of the three types of enteroadherent E coli, the EPEC primarily cause disease in neonates and young children, with most cases occurring in children < 2 years old and particularly in those < 6 months old. Unlike ETEC, the EPEC are rarely a cause of traveler’s diarrhea. Disease, however, may occur in adults if sufficiently high inocula are ingested. This organism has caused outbreaks in pediatric wards, nurseries, and day care centers and in adults that have consumed contaminated food from a buffet. The prevalence of disease in the United States is thought to be much lower than earlier in this century, but is still probably underestimated. In developing countries, the EPEC are highly prevalent and are an important cause of childhood diarrheal disease and dehydration-associated deaths. In some areas, the incidence of EPEC-associated enteritis surpasses the incidence of rotavirus infection and may represent 30%-40% of childhood diarrheal diseases.

The EAggEC are also a cause of diarrheal disease in both developing and developed countries and have caused serious outbreaks in nurseries. Infants are most commonly affected, and growth retardation may be caused by persistent diarrhea. In the United States, EAggEC have been shown to cause persistent diarrhea in patients infected by the human immunodeficiency virus (HIV).

Although not extensively studied, the DAEC seem to infect children > 1 year of age, rather than neonates.


All E coli isolates, regardless of subtype, demonstrate a typical morphology on sheep’s blood agar and chocolate agar. Colonies are typically gray and flat to slightly raised. On sheep’s blood agar, colonies produce a distinctive smell from the metabolism of tryptophan to indole and may be associated with ß-hemolysis. Most E coli strains, with the notable exception of the EIEC, rapidly ferment lactose and produce typical colonies on MacConkey and eosin methylene blue agars. Like other members of the Enterobacteriaceae, these organisms do not produce oxidase. Both the production of indole from tryptophan and the absence of oxidase activity may be detected in the laboratory through the use of rapid “spot” tests.

Many of the diarrheagenic E coli, namely the ETEC, EPEC, EAggEC, DAEC, and non-O157:H7 EHEC, demonstrate colony morphology and biochemical reactions in standard tests (biophysical profile) that are identical to normal-flora E coli. For this reason, the identification of these organisms is a problem for clinical microbiologists. If these diarrheagenic varieties are not suspected clinically and additional testing is not performed, they will be erroneously dismissed as normal flora. Fortunately, in most instances, enteritis caused by these agents is self-limited and resolves without antimicrobial therapy. The most commonly encountered EHEC strain, E coli O157:H7, and the EIEC have distinctive features that may be used to screen for these organisms.


ETEC strains have been associated with a wide variety of somatic antigens, a few flagellar antigens, and certain CFAs. In the appropriate clinical setting and in the absence of other enteric pathogens, the presence of E coli with a particular somatic:flagellar (O:H) antigen profile in the stool is supportive evidence of an ETEC infection. However, the mere presence of a particular O:H profile is not proof that a strain is toxigenic, because these antigens may also be found on nontoxigenic E coli. Definitive proof that a strain is toxigenic requires the demonstration of either enterotoxins or the genes that encode them.

Animal models and cell culture assays have been used to detect the heat-labile (LT) and heat-stable (ST) enterotoxins, but those methods have largely been replaced by immunoassays. Commercial immunoassay kits are now available for both the LT and ST toxins. Molecular assays, designed for the detection of the genes that encode for these toxins, are another method of detection. Signal amplification assays with nucleic acid probes have been used directly on stool and on colony blots of suspect isolates. Polymerase chain reaction (PCR)-based assays have also been used to detect these genes. If PCR is attempted directly on stool specimens, a preamplification treatment may be necessary to remove PCR inhibitors that are inherently present in stool. Better results may be obtained if PCR is performed on isolated colonies, rather than stool.


The most common EHEC, E coli O157:H7, has a few distinguishing characteristics that make screening for this organism possible. Escherichia coli O157:H7, unlike most E coli, does not rapidly ferment sorbitol and fails to produce ß-glucuronidase. Microbiologic assays that detect these traits have been developed to detect E coli O157:H7. A modified MacConkey plate, which contains sorbitol rather than lactose (SMAC), is the screening method most commonly used. Nonfermenting colonies on a SMAC plate may be further tested for their ability to produce ß-glucuronidase. ß-Glucuronidase is an enzyme that cleaves 4-methylumbelliferyl-ß-glucuronide and yields a UV light (366 nm)-excitable end product. Nonfermenting colonies on a SMAC plate and/or isolates that fail to produce ß-glucuronidase are then tested for the presence of the O157 antigen, usually by agglutination with type-specific antiserum. Isolates that are O157-positive are then examined for the H7 flagellar antigen by motility inhibition. Specific H7 antiserum, present in a semisolid medium, will inhibit the motility of organisms with the H7 flagellar antigen, whereas the motility of non-H7 strains is unaffected.

In South America and Australia, the non-O157:H7 EHEC serotypes cause more hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS) than the O157:H7 serotype. These serotypes are more difficult to detect, because they are able to ferment sorbitol and are therefore phenotypically similar to normal-flora E coli on the SMAC screening agar. The identification of these strains is more complicated and relies on methods to detect the shigalike toxin or verotoxin (VT), the VT gene, or other markers of pathogenicity.

Cultured Vero or HeLa cells may be used to detect the presence of VT, but this test is costly and labor intensive, and it has largely been replaced by immunoassays. A wide variety of molecular assays have been developed for the detection of EHEC. These methods include PCR-based assays and nucleic acid probes for the detection of the VT gene or other markers of pathogenicity, such as the pO157 plasmid and the eae gene encoding intimin, which is necessary for attachment to enterocytes.

Although these detection methods are not currently used in most clinical microbiology laboratories, they may be more widely used in the future. Many of these methods offer greater sensitivity than the SMAC agar, and they detect non-O157:H7 serotypes. However, problems with these technologies do exist. Substances present in stool may inhibit PCR. Some non-nucleic acid amplification methods, such as the measurement of free fecal cytotoxin or culture enhancement by using O157 immunomagnetic beads, may have sensitivities that are superior to PCR-based assays. Determining the significance of the detection of either VT or the VT gene is another problem. The presence of VT or the VT gene is supportive evidence, but not definitive proof, that the isolate is the cause of disease. There are > 200 serotypes of E coli that can express VT and only a fraction of these have been associated with HC. The serotypes O26:H11, O111:H-, O103:H2, and O113:H21 are other EHEC that have been associated with HC and/or HUS outbreaks. Therefore, when VT or the VT gene is detected in stool or stool isolates, the detection of other virulence factors or particular O:H serotypes would be necessary to further characterize the isolate.

The principal disadvantage of most molecular detection technologies is cost. In many instances, an expensive screening test is not cost effective, especially when the pathogen is infrequently encountered and less expensive screening methods exist. These technologies, however, are attractive in outbreak situations or when the incidence of disease is high.


E coli and Shigella species are so closely related that they are currently classified in the same biogroup. The EIEC have several phenotypic characteristics that are more typical of Shigella spp. than E coli. Like Shigella spp. and unlike most E coli, the EIEC are nonmotile, do not ferment lactose or ferment it only slowly, and do not decarboxylate lysine. However, complete characterization of EIEC strains discloses the presence of some biochemical features that are typical of the genus Escherichia. Nevertheless, the phenotypic differentiation of EIEC from a Shigella species is difficult, and many isolates may be misidentified as Shigella species. The isolation of an enteritis-associated bacterium that has a mixture of Shigella-like and Escherichia-like biochemical characteristics is a clue to the presence of this organism. The subsequent detection of EIEC-associated O antigen groups/O:H subtypes is useful to confirm that the organism is an EIEC.

The stool from patients with EIEC enteritis is indistinguishable from the stool of patients with shigellosis and may be watery or dysenteric. Shigella antigen testing is of no use in differentiating these bacteria, because EIEC may cross-react with Shigella antiserum. In a similar manner, tests of invasiveness, in cell culture or animal model (Sereny test), are positive with both EIEC and Shigella spp. Molecular methods, such as enzyme-linked immunosorbent assays, nucleic acid probes, or PCR, have been used for the detection of Shigella/EIEC species, but they are less useful for differentiation.

Enteroadherent E coli

The biophysical profiles of the enteroadherent E coli subtypes are indistinguishable from normal-flora E coli in routine bacteriologic studies. These varieties, which do represent distinct pathogenic subtypes, adhere differently from one another to HEp-2 cells in cell culture. The EPEC adhere to the HEp-2 monolayer in a localized pattern, the EAggEC produce three-dimensional aggregates, and the DAEC adhere diffusely. Although these adherence patterns are reliably produced, the HEp-2 assay requires cell culture capability and interpretation experience.

The EPEC can also be identified by the production of an attaching and effacing lesion (A/E) and absence of verotoxin (VT) (EHEC produce the A/E lesion, but also produce VT). If the phenotype is used for identification, it is important to demonstrate the absence of VT, because EHEC also produces an A/E lesion. Like the other diarrheagenic E coli, the EPEC have been associated with particular somatic antigens. Many of the EPEC possess specific O:H profiles that may be used for organism identification. Antiserum directed against some of these O antigens is commercially available and may be used to screen suspect colonies. A positive screening test then requires confirmation, which may include titration, complete O:H typing, or molecular analysis (see below).

Both direct DNA probes and PCR-based assays may be used for the detection of genes that encode pathogenic factors of the enteroadherent E coli. The presence of the eae gene, which is associated with the A/E phenotype, and the EAF plasmid, which contains the bfp gene cluster, are important for pathogenesis of EPEC; detection of these genes and the absence of the VT gene are important for molecular identification of the EPEC. Molecular detection of EAggEC may be accomplished by identifying a 65-MDa plasmid by either DNA probe or PCR technology. The molecular detection of the DAEC has been accomplished through the detection of a particular fimbria (F1845)-associated gene, but false positive reactions may occur.

All of the ancillary tests, both phenotypic and genotypic, used to identify the enteroadherent E coli subtypes are impractical and cost prohibitive for most clinical microbiology laboratories. These tests are most efficiently and cost-effectively performed by reference or public health laboratories that have expertise in identifying these organisms. In most instances, however, the complete identification of the enteroadherent E coli subtype is unwarranted, because most patients have a self-limited course with appropriate supportive therapy. If diarrhea from an infectious etiology becomes persistent, antimicrobial therapy is warranted and should be based on the organism’s particular antimicrobial susceptibility profile.


Regardless of the diarrheagenic E coli subtype, successful gastric transit is a prerequisite to disease. Generally, the larger the inoculating dose, the greater the likelihood that viable bacteria will survive gastric passage. Foodstuffs contaminated with bacteria buffer gastric acid and thereby facilitate gastric passage. Individuals with achlorhydria or hypochlorhydria are at an increased risk for bacterial enteritis, because the diminished gastric acidity decreases bacterial killing. The bacteria that survive gastric passage enter the small intestine and colonize the epithelium of the small intestine, colon, or both, depending on the infecting diarrheagenic E coli subtype.


The ETEC produce LT and/or ST toxins. The plasmid-encoded LT enterotoxin of the ETEC is highly homologous to a toxin of Vibrio cholerae and has the same mechanism of action. This toxin consists of two subunits, B and A. The B subunit, which binds to gangliosides on the surface of the enterocytes, facilitates entry of the enzymatic A subunit into the cytosol. The A subunit ribosylates the adenylate cyclase regulatory G protein, Gs, which results in a massive increase in cytosolic cyclic AMP (cAMP). This, in turn, results in alteration of the chloride ion channels and causes osmotic diarrhea.

One of the E coli ST toxins, STa, results in osmotic diarrhea, similar to the LT toxin, but through activation of guanylate cyclase and increased cytologic cyclic GMP (cGMP) levels. The other ST toxin, STb, does not cause alterations in cAMP or cGMP levels, but increases intracellular calcium, promotes the secretion of bicarbonate, and stimulates serotonin and prostaglandin E2 release. In addition, unlike the other toxins, STb damages enterocytes and causes epithelial cell loss and partial villous atrophy. These changes also contribute to diminished absorption and osmotic diarrhea.


The EHEC represent a variety of organisms possessing a set of virulence factors that cause HC and sometimes HUS. In the United States and Canada, the most common EHEC is E coli O157:H7. In some parts of the world, EHEC O:H serotypes other than O157:H7 are more commonly associated with HC/HUS.

The EHEC are a subset of E coli that produce disease through the combination of a variety of virulence factors. The most important virulence factor is a lysogenic bacteriophage-encoded toxin that is typical of Shigella dysenteriae type 1. This shiga toxin is also known as a VT because of its toxicity to Vero cells. VT binds to G3b, a glycolipid receptor. After binding, a portion of the VT enters the cell and disrupts protein synthesis by enzymatically altering the 28S ribosomal subunit. The high concentration of G3b on intestinal villous tip cells and renal endothelial cells may partially explain the damage to the intestine and kidneys in HC and HUS, respectively.

Although important, the presence of VT alone is probably insufficient for the production of disease, because there are VT-producing E coli, which do not produce HC/HUS. Another virulence factor of the EHEC is a chromosomal 35-kilobase locus of enterocyte effacement (LEE), as also found in the EPEC. This locus contains the eae gene, which codes for an outer membrane protein, an intimin, that mediates adherence between the EHEC and the enterocyte. This locus also confers the A/E phenotype that is typical of EHEC and EPEC. Finally, plasmid-encoded hemolysins are also probably virulence factors.


The EIEC that reach the small intestine adhere to the cell surface of mucosal enterocytes. The watery-diarrhea phase, which begins next, may be secondary to the elaboration of an enterotoxin. This enterotoxin may be encoded for by the plasmid-based gene sen. The adherent bacteria then penetrate into the cell. Cell entry is facilitated by both chromosomal and plasmid-encoded invasive factors. Within the cell, the bacterium moves through the cytoplasm by alterations in cellular actin. The EIEC then infects adjacent enterocytes. Eventually, cell death and mucosal sloughing occur, which evoke the intense inflammatory response and the dysenteric phase of the disease.

Enteroadherent E coli

The enteroadherent E coli subtypes, like all other diarrheagenic E coli, initiate pathogenesis by colonization of the intestinal mucosa. An intimate attachment occurs between bacterium and enterocyte that is distinctly different from the mucosal colonization seen with the ETEC. The enteroadherent E coli cause diarrhea without the production of better described virulence factors such as LT and ST of the ETEC or VT of the EHEC. However, some strains have been shown to produce an enterotoxin. Microbial colonization appears limited to the mucosal surface, and deep-tissue invasion is not seen, but a chromosomally encoded, cell entry gene product has been identified in some strains. Although some of the pathogenic mechanisms of these organisms have been described, to a large extent they have yet to be elucidated.

The EPEC, like the EHEC, contain a chromosomal LEE gene cluster. This locus includes the eae gene, which encodes for an intimin outer membrane protein (OMP). This OMP mediates adherence between the bacterium and the enterocyte. The LEE locus also contains the genes responsible for the attaching and effacing lesion (A/E lesion). After attaching, the bacterium causes changes that result in the effacement of the microvilli of the cell membrane, which can only be fully appreciated when viewed by electron microscopy. However, a portion of the A/E lesion, the aggregated intracytoplasmic, filamentous actin, may be detected in cell culture or intestinal biopsy by using immunohistochemical stains. Some strains may produce an enterotoxin and may contain a cell entry gene product. The precise relationship, however, between these products and the production of disease remains to be determined.

The EAggEC adhere to enterocytes via a fimbria designated aggregative adherence fimbria I or AAF/I, a 38-kDa OMP. Another fimbria (AAF/II) has also been implicated in cytoadherence. It is currently thought that, after colonization, the EAggEC promote enhanced mucus secretion. This mucus forms a protective biofilm, which contains the EAggEC and may diminish nutrient absorption. Finally, the production of enterotoxin may cause enterocyte damage and diarrhea.

Enterocyte surface adherence by the DAEC probably also occurs through the fimbriae (F1845) and/or outer membrane proteins. The precise mechanism of disease, however, remains to be determined.


The diarrhea produced by these organisms is variable and may be watery, mucoid, dysenteric, or bloody, and it may be associated with serious and even fatal systemic sequelae. The presentation and course of disease are largely dependent on the infecting E coli subtype, as well as the age and nutritional status of the patient. Infants and children, especially if malnourished, are particularly susceptible to dehydration and may succumb rapidly. The mechanism of disease production also varies with the E coli subtype. The enteritis caused by these organisms results from toxin production, enterocyte invasion, intimate bacterial/enterocyte adherence, or a combination of these mechanisms.


Clinical Findings

Patients with ETEC enteritis usually have an abrupt onset of watery diarrhea that does not contain blood, pus, or mucus (ie, is nondysenteric). The diarrhea is usually mild to moderate in severity, but some patients may have severe fluid loss, like that seen in patients with cholera. A low-grade fever, nausea, and abdominal pain may also be present. Dehydration may become severe and life threatening in neonates and children, necessitating aggressive fluid and electrolyte replacement. A self-limited course, with resolution in 2-5 days, is most common in adult travelers who acquire the disease.


Clinical Findings

Disease caused by the EHEC usually follows the ingestion of contaminated food or beverage. The incubation phase averages 3-4 days, with a range from 1 to 8 days. Individuals remain asymptomatic during the incubation phase. Early in the course of disease, patients develop watery diarrhea that is usually not bloody. Accompanying symptoms may include nausea and vomiting, abdominal cramping, and a low-grade fever. The diarrhea may then become noticeably bloody within a few days. It is interesting that fecal leukocytes are characteristically few and are detected in only ~ 50% of patient’s stools. In most patients, the disease is self-limited. However, = 10% of children and a lesser number of adults may develop HUS.

HUS is a severe systemic disease with a significant mortality. It consists of the triad of microangiopathic hemolytic anemia, renal failure, and a thrombocytopenia that may be part of a consumptive coagulopathy. The kidneys are particularly susceptible to damage (see below). In general, the kidneys may have a “flea-bitten” appearance secondary to punctate cortical hemorrhages that result from multifocal occlusion of afferent arterioles. Biopsies demonstrate microvascular deposition of immunoglobulins, complement components, and fibrin by immunofluorescence. Arteriolar and intimal hyperplasia and subintimal fibrin deposits may be seen in histologic sections. Additional findings may include microinfarcts, acute tubular necrosis, and interstitial edema. Renal failure commonly develops, with resultant oliguria, azotemia, and hematuria. Patients who survive HUS suffer morbidity caused by central nervous system and renal sequelae.


Clinical Findings

Volunteer studies and occasional, well-documented outbreaks have helped to establish the EIEC as a cause of enteritis. Patients infected by EIEC have moderate-to-severe diarrhea that begins watery, but may become dysenteric with sheets of leukocytes, blood, and mucus. The watery diarrhea is similar to that produced by ETEC infection, and the dysentery is indistinguishable from that produced by Shigella species infection. Fever and abdominal cramping are also frequently present.


Clinical Findings

The presentation and course of disease caused by the enteroadherent E coli (EPEC, EAggEC, and DAEC) are variable and depend to some degree on the infecting E coli subtype. The EPEC primarily cause acute, profuse, watery diarrhea, which rarely may become persistent. Stools are typically not bloody, mucoid, or dysenteric. Low-grade fever with nausea and vomiting may be present. Microscopic examination of the stool may disclose rare fecal leukocytes.

The EAggEC produce an acute, secretory diarrhea that is usually watery to mucoid and may also become prolonged. In some instances, gross blood may be present. A low-grade fever is common, but vomiting is infrequent.

The DAEC seem to produce a watery diarrhea, usually without blood or fecal leukocytes, but too few studies have been performed to adequately characterize this disease.

Differential Diagnosis

The differential diagnosis of diarrheal diseases is extensive and includes infectious etiologies, inflammatory-bowel disease, irritable-bowel syndrome, postsurgical dumping syndromes, and even some neoplasms, such as hypersecretory villous adenomas or vasointestinal peptide-producing neuroendocrine tumors. This extensive differential is successfully narrowed through the examination of the patient (history and physical exam), laboratory studies, and often endoscopy with biopsy

The physical examination of the patient, as well as exposure/travel history, past medical history, and the duration and presentation of current disease, yields clues to the cause of the diarrhea.

Laboratory tests, radiologic studies, and special procedures, such as endoscopy with biopsy are useful in delineating the cause of disease. A colonoscopy with biopsy is often necessary to determine the cause of persistent diarrhea, particularly when microbiologic studies are negative. Inflammatory bowel disease, ischemic colitis, lymphocytic/collagenous colitis, and neoplasia are often suspected clinically and confirmed with histopathologic studies.

The stool of patients with fever and new-onset diarrhea should be cultured for common bacterial enteric pathogens. Fecal leukocyte testing is not useful, because fecal leukocytes may be present in the stool of patients who have enteritis caused by a wide variety of pathogens, as well as in the stool of patients who have noninfectious enteritis. Clinical microbiologists use selective and differential agar media to screen the stool for Salmonella, Shigella, and Campylobacter species and for E coli O157:H7. In most laboratories, cost-effective screening for E coli O157:H7 is performed only when patients have bloody stools or a history of bloody stools. In a similar manner, the culture for even rarer bacterial enteric pathogens, such as Y enterocolitica and Vibrio species, is most often performed upon request and usually after exclusion of more typical pathogens. If bacterial agents that resemble normal flora on routine bacterial media are suspected (ETEC, EPEC, EAggEC, DAEC, or EHEC other than O157:H7), the laboratory should be notified so that confirmatory testing may be performed.

Other methods used to detect infectious agents in the stool include the direct examination, immunofluorescence enzyme-linked immunosorbent assays and cell culture-based assays. The microscopic examination of stool, often by using special stains (ie, trichrome or modified acid-fast stain), is used to detect ova and parasites. Immunoassays and ELISAs are available for the detection of Giardia lamblia, Cryptosporidium parvum, rotavirus, and Clostridium difficile toxins. Some laboratories use cell culture-based assays to detect C difficile toxin. Similar assays may be used to detect the VT of EHEC and shiga toxin of Shigella dysenteriae 1.

Individually, these microbiologic assays may be relatively inexpensive, but when numerous tests are ordered nonjudiciously, costs rapidly accrue. Microbiologic assays, like any laboratory assay, should be used to answer specific clinical questions. In patients with enteritis, the most likely causes of disease should be explored first. Patients who develop diarrhea after 3 d of hospitalization and who have been treated with antimicrobial agents probably do not warrant bacterial stool cultures or a stool examination for ova and parasites. These patients should be tested for C difficile toxin, because they are more likely to have pseudomembranous colitis.


All of the diarrheagenic E coli may produce dehydration and electrolyte abnormalities. The EAggEC may cause chronic disease and EIEC, like Shigella species, may cause a protein-losing enteropathy if dysentery is produced. Disease secondary to these agents is usually most pronounced in children, who may become dehydrated rapidly.

The most severe complication of EHEC infection is the development of HUS. This devastating disease most commonly occurs in children and has a significant mortality rate (3%-10%). Patients develop microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Patients that do not succumb may suffer significant morbidity secondary to renal and central nervous system dysfunction.


Enteritis caused by the ETEC, EPEC, EIEC, DAEC, and EAggEC is usually self-limited and may be associated with travel or a particular outbreak. In most instances, the presence of one of these organisms is assumed, and the diagnosis is based on history, physical examination, and the exclusion of other enteric pathogens. A definitive diagnosis cannot be made, unless specific assays are performed. These confirmatory assays are costly and usually clinically unnecessary. In outbreak situations, however, complete microbiologic characterization of clinical isolates, with strain analysis, may be warranted for public health purposes.

The severe sequelae that may occur secondary to EHEC infections necessitate the identification of suspicious isolates on SMAC screening agar. The diagnosis of EHEC is strongly associated with bloody diarrhea or a history of bloody diarrhea and is often associated with the ingestion of undercooked beef. The presence of E coli O157:H7 is determined by culture and serotyping.


Treatment of fluid and electrolyte loss is usually achieved through oral rehydration. The use of the World Health Organization Oral Rehydration Salts (ORS) solution is recommended. Intravenous rehydration may be necessary for infants, individuals with excessive vomiting, or those with severe dehydration.

Bismuth subsalicylate, 1 oz of liquid or two (262.5-mg) tablets taken every 30 min for 4 h, may decrease the amount of diarrhea and the duration of disease. Antimicrobial therapy is generally not indicated, because of the self-limited nature of most of these diseases. Some contend that empiric therapy may decrease symptomatology and shorten the clinical course. It is a concern, however, that the overuse of antimicrobial agents will promote resistant strains. If chronic or persistent diarrhea develops in patients infected by one of the enteroadherent E coli strains, specific antimicrobial therapy should be used. If available, the antimicrobial susceptibility profile should be used to guide therapy. If unavailable, a trial of empiric therapy for E coli is warranted (Box 2). Antimicrobial therapy has not been shown to decrease the morbidity/mortality of patients with HC/HUS. Antimicrobial therapy may worsen the clinical course, possibly by decreasing competitive enteric flora. A synthetic analog of G3b and diatomaceous earth, SYNSORB-Pk (Synsorb Biotech, Inc.), holds promise as a treatment of HC/HUS. Taken orally, this agent should absorb the VT and, it is hoped, prevent HUS.

As previously noted, disease caused by the EIEC is very much like shigellosis. It is unclear, however, if duration of disease and shedding of viable organisms by patients infected with EIEC are diminished by antimicrobial therapy, as occurs in patients with shigellosis. The diagnosis of EIEC infection requires the isolation of the organism; therefore, an antimicrobial susceptibility profile should be available to guide therapy.

Infections by the EHEC are severe and sometimes fatal. Antimicrobial therapy and antimotility agents may worsen the clinical course. Fluid and electrolyte replacement should be used as needed to treat dehydration. Transfusion, dialysis, and other supportive measures may be required for patients with HUS. Antimotility agents should not used by patients with severe infectious enteritis regardless of the etiology, but should be especially avoided by patients infected by EHEC. These drugs increase the duration and severity of disease by inhibiting the passage of the pathogenic bacteria and their toxins.

Prevention & Control

The diarrheagenic E coli, with the notable exception of EHEC, are transmitted in a human fecal-oral cycle. Most of these organisms thrive in underdeveloped countries secondarily to poor living conditions, ineffective sanitation, and unsafe drinking water. Improvements in sanitation and the quality of drinking water, as well as raising the standards of living, would greatly diminish the prevalence of these diseases (Box 3). In endemic areas, political instability, war, and a weak socioeconomic infrastructure contribute to the persistence of these organisms. Prophylactic antibiotics are not recommended for most travelers, but individuals at high risk for severe disease may benefit from antimicrobial prophylaxis. Travelers should drink bottled water and avoid eating raw, locally washed vegetables. Bismuth subsalicylate, 2 oz or two tablets four times daily, provides some prophylactic benefit, but should not be used as a substitute for other preventive measures. There are currently no vaccines approved for human use against the diarrheagenic E coli.

The EHEC inhabit the intestinal tracts of cattle and other animals. Control of this organism in its natural reservoir is currently impractical. Antimicrobial agents should not be used for its suppression in animals, because these practices provide selective pressures that promote antimicrobial resistance. Infections by the EHEC can be diminished by thoroughly cooking food, consuming only clean water and pasteurized juices, using good food preparation techniques, and maintaining good personal hygiene.

A wide variety of foods have served as vehicles for the transmission of EHEC. These include beef and beef products, dried salami, yogurt, and fresh-pressed apple cider. Of these, ground beef is especially prone to contamination and should never be eaten unless thoroughly cooked. When cooking or reheating meats, all parts of the meat should reach at least 70 °C. Children, who are at higher risk for HUS, should never be given undercooked hamburger.

Only pure, clean water should be consumed and used in food preparation. Wells, especially if they are near farms, should be periodically checked for enteric pathogens. Only pasteurized milk and juices should be consumed. Pasteurization is an effective means of eliminating EHEC, but care must be taken to avoid inadvertent postpasteurization contamination.

Good food preparation practices can also diminish the likelihood of EHEC infection. Hands should be washed thoroughly before food preparation and whenever raw meats have been touched. In addition, great care must be taken to avoid cross-contamination of foods that may not be thoroughly cooked before ingestion. Vegetables and fruits should be rinsed thoroughly under clean, free-flowing water. Cutting boards, knives, and other cooking utensils should be washed after they have been in contact with raw meat.

The infectious dose of E coli O157:H7 is so low that person-to-person transmission may occur. Anyone with EHEC HC must thoroughly wash their hands to avoid transmitting the bacteria. Children with a diarrheal disease should be carefully monitored for good hand washing. Finally, children with a diarrheal disease or history of recent diarrheal disease, especially bloody diarrhea, should avoid contact with other children, particularly contact during swimming.

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