First isolated in 1982, Shiga toxin-producing Escherichia coli O157: H7 has become an important food- and waterborne pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS) in humans. An enterohemorrhagic bacterial strain, E. coli O157: H7 infects the alimentary tract and induces abdominal cramps with hemorrhagic diarrhea. Transmission of E. coli O157: H7 occurs via the fecal-oral route after consumption of contaminated, undercooked liquids and foods. Alternatively, E. coli 0157: H7 can be transmitted by person-to-person through fecal shedding and accounts for an estimated 11% of infections. The production of Shiga toxins is a key factor contributing to the development of HUS. Enterohemorrhagic E. coli O157: H7 induces illness secondary to its production of Shiga toxin that causes a range of gastrointestinal illnesses, from watery diarrhea to hemorrhagic colitis. E. coli 0157: H7 induces enterohemorrhagic disease that can cause systemic illness by hemolytic uremic syndrome, which manifests as hemolytic anemia, thrombocytopenia, and acute renal failure. HUS can result in both acute, potentially life-threatening illness and lifelong, chronic illness.
E. coli O157:H7 has become a major, worldwide food-borne pathogen known to result in life-threatening conditions, including HUS and thrombotic thrombocytopenic purpura (TTP). Epidemiological investigation has identified cattle as the main reservoir for E. coli O157:H7 after tracing outbreaks of Shiga toxin enterohemorrhagic diarrhea to domesticated animals, particularly feedlot cattle. Ruminant animals on farms act as a natural reservoir of E. coli 0157: H7. Zoonotic transmission of E. coli 0157:H7 occurs after consumption of undercooked meat or deficiently pasteurized dairy products or contact with contaminated fomites laden with Shiga toxin enterohemorrhagic E. coli. Other causal etiologies of Shiga toxin enterohemorrhagic E. coli include exposure to contaminated water from potable drinking sources, swimming pools and lakes, contaminated food such as insufficiently cooked meats, inadequately washed leafy greens and fruits, unpasteurized drinks including apple juice, and direct contact with contaminated animals in petting farms. Contamination of fresh fruits and vegetables occurs secondary to fecal contamination in agricultural irrigation water or runoff. Although linked to other bacteria, HUS most commonly occurs after infection with Shiga toxin-producing E. coli, termed enterohemorrhagic E. coli, particularly E. coli 0157:H7. E. coli O157 has hardy survival characteristics exceeding those found in commensal E. coli strains, which enable this food-borne pathogen to survive a wide range of harsh conditions frequently encountered within the human food chain. This pathogen can persist for extended periods in the food matrix.
E. coli O157: H7 causes an estimated 63,000 hemorrhagic colitis cases annually in the United States. E. coli O157: H7-induced HUS can result in systemic morbidities, such as acute renal failure, primarily in children. E. coli 0157: H7-induced HUS has become an important etiology of acute renal failure in children over the last two decades. While E. coli 0157: H7 causes diarrheal illness in both children and adults, systemic complications occur more frequently in children. In adults, E. coli 0157: H7 colitis can occasionally cause HUS and thrombotic thrombocytopenic purpura. Outbreaks of E. coli 0157: H7 typically occur sporadically in outbreaks with exposure to contaminated food sources.
The pathogenesis of E. coli O157:H7 results from its production of Shiga toxin that injures the intestine by sloughing off of intestinal mucosa cells and results in hemorrhagic diarrhea. The Shiga toxin has systemic effects on vascular endothelial cells, resulting in a vasculitis, and manifests in hemolytic uremic syndrome, abdominal pain, and rarely, thrombotic thrombocytopenic purpura. E. coli 0157:H7 Shiga toxin initiates the inflammatory cascade that causes leukocyte aggregation, apoptosis of the affected cells, platelet aggregation, microthrombi formation, hemolysis, and renal dysfunction, as the renal glomeruli have a particular vulnerability to a microthrombi formation. E. coli 0157:H7 Shiga toxin effect manifests not only in the kidney, but in its most severe manifestations, it can result in a diffuse vasculitic injury that affects multiple organ systems and multiple organ failures.
E. coli O157: H7 attaches to the microvilli of the intestinal epithelial cells utilizing the fimbriae of the intestinal cellular walls. Bacterial attachment results in characteristic effacing lesions that flatten the microvilli as bacteria rearrange the cytoskeletal actin underneath the epithelial layer and disrupt normal intestinal cell function. Large intestinal biopsy of hemorrhagic colitis specimens demonstrates cellular hemorrhage and edema characteristic of intestinal inflammation. The histologic features resemble a pattern similar to ischemic colitis and other toxin-mediated infectious colitis like C. difficile, making E. coli O157: H7 challenging to differentiate on histology alone.
After ingestion of E. coli O157:H7, the bacteria bind to intestinal mucosa and begin releasing Shiga toxin. The toxin, in turn, disrupts protein synthesis in the epithelial cells lining intestinal mucosa, leading to cell death, sloughing of the mucosa, and eventual bloody diarrhea. Following exposure to the Shiga toxin, diarrhea, often the hemorrhagic variety, develops 3 days after exposure to the contaminated food specimen. After 3 days of diarrheal symptoms, diarrhea will become bloody in approximately 90% of affected patients. Hemorrhagic diarrheal symptoms will often resolve after 7 days, with 85% of patients having a spontaneous resolution; the remainder 15%, often children, will develop systemic manifestations, most often HUS. Chronic colonization with the post-symptomatic shedding of E. coli O157:H7 may continue to occur, leading to a persistent risk of transmission and re-infection.
Patients will classically present with acute onset of bloody diarrhea and abdominal cramping, but without fever. Diarrhea initially may not be bloody, often being watery in consistency. Most patients will not manifest a fever during initial presentation and evaluation. As a result of nausea, vomiting, and profuse diarrhea, patients will often note dehydration, asthenia, and decreased urine output. Patient history should include assessment of risk factors including (1) consumption of raw or undercooked meats or dairy products, especially unpasteurized milk, (2) exposure to ruminant animals or petting zoos, and (3) exposure to other farm scenarios.
Abdominal tenderness on physical examination reflects E. coli 0157: H7 Shiga toxin-induced intestinal vasculitis and inflammation. The abdominal discomfort from enterohemorrhagic E. coli generally manifests more severely than other forms of enteritis as a result of the hemorrhagic vasculitis. Systemic signs of dehydration such as dry mucous membranes, tachycardia, decreased skin turgor, slow capillary refill, cool extremities, and delirium, presage worsened morbidity, particularly in children.
Initial laboratory evaluation should include a complete blood count to rule out leukocytosis, hemolysis, and thrombocytopenia. A complete metabolic profile will aid in ruling out dehydration, electrolyte disturbance, and uremia. The majority of patients with E. coli 0157:H7 colitis will have a leukocytosis in excess of 10,000/microL. Initial diagnosis of E. coli O157:H7 utilizes stool culture of a diarrheal sample within the first days after onset. Most cultures positive for E. coli 0157:H7 will come from patients complaining of hemorrhagic diarrhea or grossly bloody diarrheal samples. Despite the Centers for Disease Control and Prevention recommendation that all diarrheal samples submitted for culture undergo screening for E. coli O157:H7, many laboratories will not routinely screen for this organism necessitating the clinician to specifically request testing for E. coli 0157:H7. Culture the diarrheal specimen with sorbitol MacConkey agar, which allows for differentiation of non-pathogenic E. coli from pathogenic E. coli O157 based on the latter’s inability to metabolize sorbitol. Diagnostic confirmation utilizes testing for the presence of E. coli O157:H7 antigens in the stool or toxin genes with polymerase chain reaction. Commercially available enzyme-linked immunosorbent assays can detect Shiga toxins in hemorrhagic stool samples.
Treatment of E. coli 0157: H7 gastrointestinal infection focuses on supportive care and maintenance of hydration status. Most enterohemorrhagic E. coli diarrheal patients recover without treatment within 10 days other than fluid replacement. Antibiotic treatment has not had a beneficial effect in speeding resolution or preventing complications from E. coli 0157: H7; additionally, evidence exists that antibiotics worsen outcomes by increasing the likelihood of development of HUS, possibly secondary to antibiotic-induced lysis of infectious organisms with the precipitous release of Shiga toxin into systemic circulation. Patients with severe manifestations of HUS may benefit from hemodialysis to treat volume, electrolyte, and uremia issues related to the acute renal failure. Limited data suggest that the monoclonal antibody eculizumab may expedite recovery from E. coli 0157: H7 HUS. Eculizumab acts by inhibiting the complement cascade thereby interfering with the recruitment of inflammatory cells and attenuating damage to the renal vasculature. Notably, eculizumab, an extremely expensive pharmaceutical with a primary indication for treatment of paroxysmal nocturnal hematuria, lacks clinical consensus for the treatment of E. coli O157 associated HUS and typically gets utilized as a rescue agent in the sickest patients. Antiperistaltic agents, such as loperamide or dicyclomine, slow intestinal motility and increase the risk of systemic complications; clinicians should avoid their utilization in this setting.
The differentiation of E. coli O157: H7 from other invasive intestinal bacterial pathogens inducing hemorrhagic dysenteries such as Salmonella, Shigella, Campylobacter, Yersinia, and C. difficile has a meaningful clinical impact in that antibiotic therapy often aids in recovery from these other pathogens. Noninfectious etiologies of hemorrhagic diarrhea such as ischemic colitis, mesenteric ischemia, Crohn disease, and ulcerative colitis merit consideration as well.
Enterohemorrhagic E. coli colitis has a good prognosis for recovery when patients do not have systemic manifestations of diarrheal illness. HUS complicates up to 10% of E. coli 0157:H7 cases, with higher risk reported for younger children, especially those under 5 years old. When patients develop HUS complications, the risk of mortality approaches 5%.
Although most with enterohemorrhagic diarrhea-associated HUS recover from the acute illness episode, these patients have the potential for persistent, long-term renal dysfunction and extrarenal complications including seizures, diabetes, chronic colitis, and hypertension. HUS, the most frequent, severe complication of E. coli O157:H7 colitis, occurs most commonly in children, especially young children less than 5 years-old, and in the elderly. HUS manifests 5 to 10 days following the onset of hemorrhagic diarrhea and presents with the triad: hemolytic anemia, acute kidney failure, and thrombocytopenia. Approximately 10% of children with an E. coli O157:H7 infection will develop HUS, which carries an annual 5% mortality rate, and those who survive have an increased risk for developing chronic kidney disease. Shiga toxin enterohemorrhagic-induced HUS in the elderly causes significant morbidity and mortality. E. coli 0157:H7 infections result in healthcare costs in the United States of over US$ 400 million annually. As 10% of E. coli 0157:H7 hemorrhagic colitis cases progress to HUS with worsened prognosis, prevention of Shiga toxin enterohemorrhagic infections would improve health outcomes and reduce healthcare expenditures.
Nephrology consultation has merit if patients develop HUS, as up to 50% require hemodialysis if acute renal impairment occurs. Gastroenterology or infectious disease consultations may also provide expert guidance, especially in the initial diagnostic evaluation patient care phase, when trying to differentiate E. coli O157: H7 from other infectious, inflammatory, or ischemic etiologies of bloody diarrhea.
Potential means of preventing HUS include minimizing fecal Shiga toxin enterohemorrhagic shedding in animals and transmission of infection to humans. Public health measures to safeguard food and water from contamination remain essential in addition to personal hygiene and special care of food preparation and storage. Preventing the spread of E. coli 0157:H7 hemorrhagic colitis includes isolation of potentially infectious contacts in school or within institutions to minimize infectious transmission. Ample evidence suggests that personal hygiene, particularly handwashing, effectively prevents infectious acquisition and spread of E. coli 0157:H7 infections in the community, thereby altering the risk of HUS. Public health education, guidelines and legislation to safeguard food and water against Shiga toxin enterohemorrhagic E. coli food and water contamination and to ensure safe food production, preparation, and storage of food will benefit society as a whole. Research investigating altering bovine intestinal conditions with different feeds as a means of reducing fecal E. coli 0157:H7 shedding has demonstrated that cattle fed hay rather than grain for a brief period before slaughter has reduced fecal shedding of pathogenic E. coli. Developing a human vaccine to prevent enterohemorrhagic E. coli infection may eventually provide herd immunity, protect against HUS, and provide value in low-income, high-risk dysentery settings.