INTRODUCTION — Escherichia coli are normal inhabitants of the human gastrointestinal tract and are among the bacterial species most frequently isolated from stool cultures. When E. coli strains acquire certain additional genetic material, they can become pathogenic; these pathogenic clones circulate widely and are among the most virulent enteric pathogens. Diarrheagenic E. coli are among the most frequent bacterial causes of gastroenteritis worldwide.
The most common diarrheagenic clones can be assigned to specific pathotypes, which have distinct pathogenic, epidemiologic, and clinical characteristics (table 1) [1]. The characteristics of diarrheal illness caused by the following pathotypes will be reviewed here:
●Enterotoxigenic E. coli (ETEC)
●Enteropathogenic E. coli (EPEC)
●Enteroinvasive E. coli (EIEC)
●Enteroaggregative E. coli (EAEC)
Shiga toxin-producing E. coli (STEC) is discussed in greater detail separately. (See "Shiga toxin-producing Escherichia coli: Microbiology, pathogenesis, epidemiology, and prevention" and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)
COMMON CLINICAL CONCEPTS
Microbiology — E. coli can be cultured readily from the stool under aerobic conditions. On selective media, such as MacConkey agar, E. coli usually appear as dark pink colonies, indicating that the organism ferments lactose (picture 1). Additional biochemical identification should also be performed, since up to 10 percent of E. coli do not ferment lactose or ferment lactose relatively slowly. The most useful biochemical identification test for E. coli is the indole test, which is positive in up to 99 percent of E. coli strains.
Pathogenic E. coli are not distinguishable from other strains or from each other by the appearance on culture plates or by the results of the usual biochemical tests. To determine whether the isolated strain is one of the pathogenic clones or merely a nonpathogenic constituent of the intestinal microbiota, one must employ additional identification techniques; such tests are increasingly available in diagnostic laboratories. (See 'Clinical diagnosis' below.)
Enterohemorrhagic E. coli (EHEC) O157:H7 is the only pathogenic strain that can be identified readily in the clinical laboratory using nonmolecular tests [2]. Such testing can include determining the serotype of the strain and biochemical characteristics demonstrable on agar plates.
The virulence traits are distinct for each category of pathogenic E. coli [3]. These virulence traits include adherence factors that allow E. coli to attach to the intestinal mucosa, and toxins that interrupt normal intestinal cell secretion and absorption (secretory toxins) or that damage the intestinal cell (cytotoxins). These adherence factors and toxins are encoded on accessory genetic elements in E. coli, such as plasmids, transposons, and bacteriophages.
Clinical diagnosis — Identification of one of these pathogenic E. coli isolates through molecular testing on stool in a patient with diarrhea is generally sufficient to make the clinical diagnosis of an E. coli infection. However, a high degree of clinical correlation is necessary, and some caveats are warranted.
Prior to the increasing availability of commercial molecular tests for diagnosis of diarrheal pathogens, E. coli pathotypes (apart from EHEC O157:H7) were not readily identifiable in the clinical setting, as they are indistinguishable from each other and nonpathogenic E. coli on culture and biochemical testing. (See 'Microbiology' above.)
In the clinical context of stool molecular testing, the relevant gene targets are identified relatively frequently among patients with diarrhea. Given the mosaic nature of the E. coli genome, any of these gene targets may detected in isolation; detection of a single gene target is not equivalent to detection of a pathogen. Moreover, test results may reflect the presence of nonviable organisms or a clinically insignificant pathogen burden [4].
For these reasons, we interpret stool molecular test results together with the corresponding clinical context:
●For stool testing demonstrating enteroaggregative E. coli (EAEC) and enteropathogenic E. coli (specifically presence of the eae gene in isolation), the clinical context should consist of diarrhea in the absence of a more likely etiology.
●For stool testing demonstrating genes with heat-labile or heat-stable enterotoxins, the clinical context should consist of travel to areas with endemic enterotoxigenic E. coli (ETEC).
●For stool testing demonstrating a gene-encoding Shiga toxin, this may be presumed to represent Shiga toxin-producing E. coli (STEC) infection, given the epidemiologic and clinical risk associated with this pathogen. Details regarding diagnosis of EHEC are discussed separately. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Microbiologic diagnosis'.)
Approach to treatment — Supportive care with fluid, electrolyte, and nutritional management is the cornerstone of treatment of diarrheal illnesses. (See "Approach to the adult with acute diarrhea in resource-rich settings", section on 'Management' and "Approach to the adult with acute diarrhea in resource-limited countries", section on 'Treatment' and "Approach to the child with acute diarrhea in resource-limited countries", section on 'Treatment'.)
For patients with diarrhea who have a pathogenic E. coli identified on stool testing, we suggest not routinely administering antibiotic therapy. Antibiotics can be effective in reducing the duration of diarrhea associated with pathogenic E. coli. However, most cases of diarrhea associated with E. coli resolve spontaneously and antibiotic therapy is associated with selection of resistant organisms and other adverse effects. Additionally, antibiotic therapy is not recommended in cases of Shiga toxin-producing E. coli infection because of the association with hemolytic uremic syndrome. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment", section on 'Antibiotics'.)
Antibiotic therapy is reasonable in patients with diarrhea associated with pathogenic E. coli infection (other than STEC such as E. coli O157:H7) that is severe (eg, with fever, more than six stools per day, volume depletion warranting hospitalization) or bloody. Antibiotic therapy is also reasonable in patients with prolonged (>7 days) diarrhea, particularly if no other pathogen has been identified. A lower threshold for antibiotic therapy is appropriate in patients who are at risk for more severe or persistent infection, such as immunocompromised patients.
When antibiotic therapy is indicated, azithromycin or a fluoroquinolone is generally an appropriate choice. For infectious diarrhea, azithromycin is given as a single 1 g dose (for patients without dysentery) or as 500 mg once daily for three days. Appropriate fluoroquinolones include ciprofloxacin (a single 750 mg dose or 500 mg twice daily for three to five days) and levofloxacin (500 mg as a single dose or given once daily for three to five days). Studies evaluating the efficacy of antibiotics for particular E. coli pathotypes are limited. Azithromycin and fluoroquinolones have been effective for ETEC in trials of travelers' diarrhea [5,6]. Similarly, several small trials have demonstrated that diarrhea resolved faster when EAEC was cleared from the stool with ciprofloxacin [7,8].
Antibiotic resistance among ETEC and EAEC is common. However, since these pathotypes are identified primarily with culture-independent techniques, having a pathogen on hand for susceptibility testing to inform optimal antibiotic selection is unusual.
Our treatment approach is consistent with the Infectious Diseases Society of America clinical practice guidelines on infectious diarrhea [9].
ENTEROTOXIGENIC E. COLI
Epidemiology — Enterotoxigenic E. coli (ETEC) causes watery diarrhea in young humans and other mammals in resource-limited settings, as well as in older individuals who have not previously been exposed to the organism [10].
Approximately 108 to 1010 ETEC must be ingested to induce diarrhea in an otherwise healthy individual [1]; exposure to this large an inoculum occurs commonly in resource-limited settings since the pathogen thrives in food and water supplies in the absence of adequate sanitation. ETEC is one of the most common bacterial causes of dehydrating diarrheal illness in children under two years of age in these regions [11,12]. These strains can also cause diarrhea in travelers to tropical regions who are exposed to contaminated food and water. In addition, ETEC is emerging as a significant diarrheal pathogen in some resource-rich regions [13-15]. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Pathogenesis — The pathogenesis of disease due to ETEC consists of ingestion of bacteria, intestinal colonization, and elaboration of virulence factor(s).
ETEC must express colonizing fimbriae (CFs) to permit the attachment of the bacteria to the intestine. Antibodies to fimbrial adhesins, specifically colonization factor antigen I, have been shown to be protective in a mouse model [16].
Upon colonization, ETEC elaborates one or both of two major classes of plasmid-encoded secretory toxins: heat-labile toxin (LT) and heat-stable toxin (ST) [17]. Only E. coli that contain one or both of these toxin classes are classified as ETEC [18].
●LT is a complex family of toxins related to Vibrio cholerae cholera toxin with respect to structure, function, and mechanism. LT acts by stimulating adenylate cyclase and increasing intracellular cyclic adenosine monophosphate (AMP), which induces secretion of chloride from intestinal crypt cells and inhibition of absorption of sodium chloride at the villus tips. Secretion of free water into the intestinal lumen follows, manifesting clinically as watery diarrhea [19]. Studies suggest that LT and its secretion apparatus can cluster at one end of the bacterial organism, which may permit ETEC to focus toxin delivery to the host intestinal cell [20]. (See "Cholera: Microbiology and pathogenesis".)
●There are two major STs that may be present in ETEC; only one of these, STa, is associated with human disease. STa may exist as a human allele (designated "h") or a porcine allele ("p"). Epidemiologic data are inconclusive with regard to the relative pathogenicity of these alleles. Both STa alleles activate enterocyte cyclic GMP, which leads to the stimulation of chloride secretion and inhibition of sodium chloride absorption. The end result is secretion of free water into the intestinal lumen, which manifests clinically as watery diarrhea [19].
Clinical features — ETEC infection has a short incubation period (one to three days), and the onset of symptoms and signs is rapid. Diarrhea is watery and may be mild or severe. Patients may report nausea, but vomiting is relatively uncommon. The illness is self-limiting, lasting one to five days. (See "Travelers' diarrhea: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Molecular diagnosis — The diagnosis of ETEC is made by molecular detection of the genes for LT or ST [21,22]. Polymerase chain reaction (PCR) or molecular panels that identify ETEC are available in many clinical laboratories.
Classically, these organisms had previously been identified by bioassays for the secretory toxins: the rabbit ileal loop for LT and the suckling mouse assay for ST, but these research tests have been replaced by molecular testing in many clinical laboratories.
ENTEROPATHOGENIC E. COLI — Enteropathogenic E. coli (EPEC) strains are defined by the characteristic "attaching and effacing" effect they elicit upon interaction with epithelial cells and by the fact that they do not produce Shiga toxin (figure 1).
Epidemiology — Typical and atypical EPEC strains have been distinguished based on the presence of certain virulence factors (see 'Pathogenesis' below). Typical EPEC (tEPEC) has been associated with severe sporadic diarrheal illness and diarrhea outbreaks, most commonly among children less than six months of age (and almost exclusively in children <2 years of age) in resource-limited countries [23,24]. Atypical EPEC (aEPEC) are less well understood; limited epidemiologic studies suggest that aEPEC may occur at all ages and in resource-rich countries. Nevertheless, evidence suggests that some aEPEC are diarrheal pathogens [25]. (See 'Approach to treatment' above.)
Pathogenesis — Typical EPEC (tEPEC) harbor a virulence plasmid (pEAF) that encodes the bundle-forming pilus (BFP), the factor required for colonization. In addition, tEPEC carry the Locus for Enterocyte Effacement (LEE) chromosomal island, which contains the eae gene, which encodes an outer membrane protein colonization factor called intimin. To be designated tEPEC, an E. coli strain must possess both pEAF and the eae gene; isolates that have only eae are considered atypical EPEC (aEPEC).
The site of EPEC infection is thought to be the small intestine. The steps in pathogenesis of tEPEC for initiation of diarrheal illness include [26-29]:
●Initial localized adherence of the organisms to the enterocyte via the BFP
●Induction of signal transduction in the enterocyte by protein toxin secretion
●Development of intimin-mediated intimate adherence to the enterocyte
As above, both tEPEC and aEPEC express the LEE chromosomal island, which elaborates, in addition to intimin, a set of >20 protein toxins that are injected directly into the target epithelial cell. Injection of protein toxins is effected by a complex nanomachine called a type III secretion injectisome [30,31]. The type III "effector" toxins are thought to act by binding to protein elements of the cell's signal transduction apparatus, resulting in a complex series of events that transform a normally absorptive epithelial cell into a secretory dynamo [32]. This is accompanied by mobilization of intracellular calcium, activation of protein kinase C and the myosin-light-chain kinase, and induction of tyrosine phosphorylation of proteins [33]. The effectors induce rearrangement of cytoskeletal proteins, resulting in the classic "attaching and effacing" lesion, alterations in water and electrolyte secretion, and increased permeability of intestinal tight junctions.
EspF is an LEE-secreted protein that is not involved with attaching and effacing; it appears to disrupt intestinal barrier function by increasing monolayer permeability via alteration of electrical resistance [34]. EspF has several protein-protein interaction domains that may function by interacting with endocytic regulation [35]. Two other secreted proteins, EspG and EspG2, inhibit luminal membrane chloride absorption by decreasing surface expression of the Cl-/OH-exchanger via disruption of microtubules [36].
Clinical features — The diarrhea associated with tEPEC in children can be severe, with concomitant vomiting and dehydration. Stools are typically watery without blood or pus. Fever may occur in a minority of patients. Diarrhea due to aEPEC is also watery and not as severe as that caused by tEPEC.
If diarrhea persists, malnutrition can be a devastating complication, particularly in resource-limited settings, where resources for supportive therapy may be limited. Micronutrient malnutrition in severe infection may also be a result of direct mechanisms, as suggested by cell culture data demonstrating that EPEC infection inhibits intestinal absorption of thiamine [37].
Molecular diagnosis — The gold standard for identification of tEPEC is the molecular detection by panel or polymerase chain reaction (PCR). Such tests identify either the pEAF plasmid or its encoded bundle-forming pilus (BFP); these tests produce equivalent results. BFP is not found in strains lacking the LEE chromosomal island (tEPEC is defined by the presence of both the pEAF/BFP and the LEE).
In contrast, tests that target the LEE (via detection of the eae gene, which encodes intimin) can identify isolates that lack the pEAF (by definition, aEPEC). While aEPEC strains have been implicated in diarrhea outbreaks [25], it is likely that not all strains harboring only the eae gene are human pathogens. Thus, treatment of potential aEPEC infections should only be considered in the absence of another pathogen.
ENTEROINVASIVE E. COLI — Enteroinvasive E. coli (EIEC) is closely related to Shigella and causes colitis that is similar to shigellosis. Clinical EIEC infection appears to be uncommon, although it may be underdiagnosed. Clinical disease with EIEC begins as watery diarrhea and may or may not proceed to bloody diarrhea and frank dysentery. Infection can result in severe disease. In a rare outbreak of EIEC infection in the United States that involved 52 individuals who had attended a potluck party, 28 (54 percent) were hospitalized and 13 (25 percent) had sepsis [38]. Among the subset interviewed about their symptoms, median onset was 20.5 hours after exposure, 77 percent had watery diarrhea, 54 percent had mucoid diarrhea, and 91 percent had fever.
The organisms can be detected using nucleic acid tests, including multiplex panels. EIEC invades the intestinal cell, multiplies intracellularly, and extends into the adjacent intestinal cells. The same genes facilitate pathogenesis of both EIEC and Shigella [39]. EIEC may be differentiated from Shigella principally by the fact that EIEC strains ferment glucose and xylose. (See "Shigella infection: Epidemiology, microbiology, and pathogenesis" and "Shigella infection: Clinical manifestations and diagnosis".)
ENTEROAGGREGATIVE E. COLI — Enteroaggregative E. coli (EAEC) was first described in the 1980s, when collections of E. coli from studies of patients with diarrhea in resource-limited settings were examined in tissue culture adherence assays [40]. E. coli that had a distinctive palisading adherence on human epithelial type 2 (HEp-2) cells were observed more frequently in the stools of children with diarrhea than in children without diarrhea [41].
Epidemiology — EAEC appears to be a cause of acute and chronic diarrheal illness among many different subpopulations in both resource-limited and resource-rich regions.
Surveys of E. coli from diarrhea outbreaks in Europe have demonstrated the presence of EAEC in both outbreaks and sporadic cases of diarrhea [42,43]. In a prospective study of patients presenting with diarrhea to two large medical centers in the United States, EAEC was observed in 4.5 percent of cases and was identified more frequently among cases than asymptomatic controls [44]. One meta-analysis noted a positive correlation between acute diarrheal illness and EAEC excretion (diagnosed by aggregative adherence assay) in the following groups [45]:
●Children residing in both resource-limited and resource-rich regions
●Adults with and without human immunodeficiency virus (HIV) infection residing in resource-limited regions
●International travelers to resource-limited regions
EAEC has also been repeatedly associated with persistent diarrhea among children studied from Chile, Brazil, Mexico, India, and Bangladesh [46-52], and has been associated with persistent diarrhea among adults with HIV infection, particularly those with advanced immune suppression, in the United States and Switzerland [53,54].
As with many diarrheal pathogens, not all studies have identified a link between EAEC and clinically significant diarrhea [12,55]. We consider treatment of patients shedding EAEC in the setting of clinically significant diarrhea in the absence of another likely pathogen.
In a large multi-center, case-control study among children younger than five years of age in sub-Saharan Africa or south Asia, EAEC was extremely common among both children with diarrhea and controls and was not epidemiologically associated with moderate-to-severe diarrhea [12]. However, a multi-center longitudinal study of children in resource-limited countries suggested that asymptomatic carriage of EAEC could predict linear growth retardation [56]. This association has been previously reported in individual studies [57] and suggests that the burden of EAEC disease may more closely parallel asymptomatic carriage than watery diarrhea.
Pathogenesis — The pathogenesis of diarrhea caused by EAEC is incompletely elucidated [41]. EAEC are capable of inducing the release of interleukin (IL)-8 from polarized colonic T84 cells [58] and inducing epithelial barrier dysfunction [59].
Most EAEC strains harbor a transcriptional activator called AggR [60]; AggR activates a large number of genes that are likely involved in pathogenesis. EAEC strains that possess AggR and its regulon are termed typical EAEC strains. Given that most epidemiologic studies addressing EAEC detect the organism by virtue of AggR-dependent genes, most of what is known about EAEC involves typical strains.
A variety of EAEC pathogenetic mechanisms have been postulated:
●Adherence fimbriae (variants AAF/1-AAF/V) are present in nearly all typical EAEC strains, and the AAF-encoding genes are directly controlled by AggR itself [61]. AAF-encoding genes are carried on a virulence plasmid (pAA) in typical EAEC; pAA also encodes AggR. An AggR-activated and pAA-encoded protein called dispersin (encoded by the aap gene) appears to promote AAF-mediated colonization [62].
●Mucosal destruction has been demonstrated in clinical specimens and in tissue culture assays, and a protease cytotoxin has been identified in many EAEC strains [63]. Serine family proteases are commonly found in EAEC and may be associated with diarrheagenic strains [64].
●Some EAEC strains may invade tissue culture cells and induce IL-8 production via mitogen-activated protein kinase [65,66].
Clinical features — As above, both acute and chronic diarrhea have been associated with EAEC. Patients with symptomatic infection typically present with watery diarrhea without blood in the stools. In one study that included 37 patients with EAEC-associated diarrhea, concomitant fever, abdominal pain, and vomiting were reported in 43, 65, and 57 percent, respectively [44].
In 2011, a typical EAEC strain that had become lysogenized with a Shiga toxin-encoding phage was associated with a large multi-country outbreak of hemorrhagic colitis and hemolytic uremic syndrome (HUS) [67]. This outbreak, responsible for 52 deaths, was linked to contaminated fenugreek sprouts. The implicated strain has not been isolated since the outbreak, although other Shiga toxin-producing EAEC have been isolated. Whether these clones will emerge epidemiologically remains to be seen.
Molecular diagnosis — The gold standard for the diagnosis of EAEC is detection of the AggR regulon using molecular techniques. Commonly available molecular panels detect EAEC this way. Although no single deoxyribonucleic acid (DNA) target has been epidemiologically linked to pathogenicity, the linkage of the AggR regulon with pathogenesis suggests that targeting any number of AggR-activated genes for detection will produce similar diagnostic performance.
Other methods for identifying EAEC include detection of aggregative adherence to HEp-2 cells in culture; EAEC has a distinctive palisading adherence pattern. While not used in clinical laboratories, research studies have used this technique for diagnosing cases [45].
SHIGA TOXIN-PRODUCING AND ENTEROHEMORRHAGIC E. COLI — Some strains of E. coli produce Shiga toxin. Shiga toxin-producing strains that also demonstrate an "attaching and effacing" lesion like enteropathogenic E. coli (albeit in the colon, not the small intestine) are categorized as enterohemorrhagic E. coli (EHEC). A particularly virulent subset of EHEC organisms belongs to serotype O157:H7 [2,68]; non-O157 serotypes also account for a large proportion of EHEC infections (figure 1).
EHEC strains, especially those belonging to serotype O157:H7, have been responsible for large outbreaks of bloody diarrhea, some associated with hemolytic uremic syndrome, a triad of microangiopathic anemia, renal failure, and thrombocytopenia [69,70].
Shiga toxin-producing E. coli infection is discussed further elsewhere. (See "Shiga toxin-producing Escherichia coli: Microbiology, pathogenesis, epidemiology, and prevention" and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)
Shiga toxin-associated hemolytic uremic syndrome is discussed further separately. (See "Clinical manifestations and diagnosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children" and "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children".)
OTHER E. COLI STRAINS — There are no good data supporting the association of other types of E. coli (eg, diffusely adherent E. coli, detaching E. coli) with diarrhea. However, since E. coli are ubiquitous and have a demonstrated capacity for acquiring the DNA for virulence traits from other organisms, additional groups of E. coli will probably be associated with diarrheal disease in the future.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Travelers' diarrhea (The Basics)" and "Patient education: E. coli diarrhea (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Pathogenic Escherichia coli – E. coli are normal inhabitants of the human gastrointestinal tract. When E. coli strains acquire certain additional genetic material, they can become pathogenic. E. coli are among the most frequent bacterial causes of diarrhea. (See 'Introduction' above.)
●Features – The different E. coli pathotypes have distinct epidemiologic, clinical, and pathogenic features (table 1):
•Enterotoxigenic E. coli (ETEC) – ETEC survives readily in water and food and is one of the most common bacterial causes of dehydrating diarrheal illness in children under two years of age in resource-limited regions. ETEC can also cause diarrhea among travelers to tropical regions and is emerging as a pathogen in resource-rich settings. ETEC causes primarily watery diarrhea through plasmid-encoded toxin production. (See 'Enterotoxigenic E. coli' above.)
•Enteropathogenic E. coli (EPEC) – EPEC has been associated with sporadic diarrheal illness and diarrhea outbreaks, most commonly among children under six months of age in resource-limited countries. EPEC strains are defined by their characteristic "attaching and effacing" effect upon interaction with epithelial cells and by the fact that they do not produce Shiga toxin. EPEC proteins affect cell physiology through adherence and induction of signal transduction. (See 'Enteropathogenic E. coli' above.)
•Enterohemorrhagic E. coli (EHEC) – EHEC strains are capable of producing Shiga toxin and, like EPEC strains, demonstrate an "attaching and effacing" lesion. EHEC strains, especially those belonging to serotype O157:H7 (and also O104:H4) have been responsible for large outbreaks of bloody diarrhea, some associated with hemolytic uremic syndrome. (See 'Shiga toxin-producing and enterohemorrhagic E. coli' above and "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)
•Enteroinvasive E. coli (EIEC) – EIEC infection appears to be uncommon. Clinical disease begins as watery diarrhea that may progress to bloody diarrhea and dysentery. EIEC is closely related to Shigella, and the same genes facilitate pathogenesis of both organisms. EIEC invades the intestinal cell, multiplies intracellularly, and extends into the adjacent intestinal cells. (See 'Enteroinvasive E. coli' above.)
•Enteroaggregative E. coli (EAEC) – EAEC is associated with persistent and acute diarrheal illness among many demographic groups in both resource-limited and -rich settings and may be associated with linear growth retardation. On tissue culture adherence assays, EAEC has a distinctive palisading adherence on human epithelial type 2 (HEp-2) cells. The pathogenesis of diarrhea caused by EAEC is incompletely elucidated. (See 'Enteroaggregative E. coli' above.)
●Microbiology – E. coli can be cultured readily from the stool under aerobic conditions. However, pathogenic E. coli are not distinguishable from nonpathogenic strains or from each other by their appearance on culture plates or by the results of the usual biochemical tests. E. coli O157:H7 (EHEC) is the only pathogenic strain that can be identified readily without molecular testing. With the increasing availability of commercial molecular tests for diagnosis of diarrheal pathogens, other E. coli pathotypes are being identified more frequently. (See 'Microbiology' above.)
●Clinical diagnosis – Identification of one of these pathogenic E. coli isolates through molecular testing on stool is not tantamount to an E. coli infection. Clinical correlation is required, along with consideration of potential alternative etiologies. A positive test in an asymptomatic patient does not indicate infection. (See 'Clinical diagnosis' above.)
●Management (See 'Approach to treatment' above.)
•Supportive care – Supportive care with fluid, electrolytes, and nutritional management is the cornerstone of treatment of diarrheal illnesses.
•Role of antibiotics
-For patients with diarrhea who have a pathogenic E. coli identified on stool testing, we suggest not routinely administering antibiotic therapy (Grade 2C).
-Antibiotic therapy (eg, with azithromycin or ciprofloxacin) is reasonable in patients with severe, bloody, or persistent diarrhea, particularly in children or immunocompromised hosts.
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Christine A Wanke, MD, who contributed to an earlier version of this topic review.
