Escherichia coli (e Coli 0157 H7)

Etiology

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). The 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. The 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.[4][5][6]

Epidemiology

E. coli O157: H7 causes an estimated 63,000 hemorrhagic colitis cases annually in the United States. Review of database and studies from 10 out of 14 world health organizations subregions showed the global incidence of E. coli to be 2.8 million cases per year. 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.

Pathophysiology

The infectious dose of E.coli O157: H7 is, however low. One study shows that as few as ten viable bacteria can cause disease in humans. 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 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.[7]

Histopathology

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.

Toxicokinetics

After ingestion of E. coli O157: H7, the bacteria bind to the 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 three days after exposure to the contaminated food specimen. After three days of diarrheal symptoms, diarrhea will become bloody in approximately 90% of affected patients. Hemorrhagic diarrheal symptoms will often resolve after seven 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.

History and Physical

Patients will classically present with acute onset of bloody diarrhea and abdominal cramping, usually without fever. Diarrhea initially may not be bloody, often being watery in consistency. Most patients will not manifest a temperature during the 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, cold extremities, and delirium, presage worsened morbidity, particularly in children.

Evaluation

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 above 10,000/microL. Initial diagnosis of E. coli O157: H7 utilizes the 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 request testing for E. coli 0157:H7 specifically. 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.[8][9][10]

Treatment / Management

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 ten days other than fluid replacement. Antibiotic therapy 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 sudden release of Shiga toxin into the systemic circulation. Patients with severe manifestations of HUS may benefit from hemodialysis to treat volume, electrolyte, and uremia issues related to 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.[4][11](B3)

Differential Diagnosis

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.

Prognosis

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%.

Complications

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.