Managing Escherichia coli O157:H7 infections
Diagnosis, treatment vexing but improving
Escherichia coli outbreaks this summer in Georgia, Maine, and Wyoming continue to underscore how weak the drug arsenal is against the bacteria. With no known treatment, little understanding of its mechanism of action, and symptoms that can be blamed on a number of conditions, even properly diagnosing an infection can be a challenge.
The main weapons used to combat E. coli continue to be solid reporting systems and specific lab cultures - areas where there have been improvements.
The number of states requiring E. coli reporting to federal health officials has grown from two in 1987 to 32 today. Within that time, the number of outbreaks reported has grown from four in 1992 to 30. Currently, federal health officials estimate about 20,000 infections and 250 deaths each year can be attributed to E. coli.
What makes E. coli 0157:H7 particularly virulent is its extra set of genes. These genes allow the bacteria to stick to the walls of the intestine to produce Shiga toxins, which cause bleeding. Once E. coli enters the bloodstream, other vessels are damaged, particularly in the kidneys, where blood vessel damage can lead to kidney failure.
Born largely from contaminated feces or undercooked beef, the bacteria are known to be present in about 1% of healthy cattle. In adults, the diarrhea, cramping, and fever usually run their course after an unpleasant two to three weeks. Experts caution against the use of standard antibiotics, as their effectiveness can cause the bacteria to release a host of toxins. Therefore, fluids and simple monitoring are the mainstays in treating adults.
For children, though, the amount of red blood cells and platelets destroyed by the bacteria's toxins always should be considered life-threatening.
"We know that infection with this organism is a common cause of bloody and non-bloody diarrhea, and that E. coli is responsible for most cases of hemolytic uremic syndrome [HUS], which is a major cause of acute renal failure in children," says Thomas Boyce, MD, of the federal Centers for Disease Control and Prevention in Atlanta.
This summer's worst outbreak occurred in Alpine, WY, where 62 confirmed cases were reported to federal officials, the majority being adult patients. Health officials there contained the outbreak, attributing it to wild elk feces washing into the town's natural springs water supply. Health officials have barred use of the springs for drinking water until tests are completed, leaving existing well water as the area's main supply.
In Atlanta, 26 children were diagnosed with E. coli after coming into contact with the bacteria at a water park. The original source of the outbreak has been traced to contaminated meat eaten by a young visitor to the park living several counties away. The bacteria most likely spread through exposure to fecal matter or person-to-person contact.
A 2-year-old who visited the water park died after contracting HUS and falling into a coma. She was being treated with transfusions, dialysis, and intravenous feeding, the type of life support techniques that are the only current options while clinical trials of an investigational drug to treat HUS move forward.
Treatment and diagnosis keys
According to the CDC, the typical incubation period for E. coli is three to four days. The condition usually begins with severe abdominal cramps and non-bloody diarrhea that turns bloody by the second or third day. About 50% of patients have nausea and vomiting as well.
Overall, E. coli can cause asymptomatic infection, bloody or non-bloody diarrhea, thrombocytopenia, purpura, and HUS primarily. E. coli infection also can manifest through a low-grade fever or the absence of fever, adding to the challenge of a proper diagnosis.
According to Boyce, the symptoms often mirror those of gastrointestinal hemorrhaging or worse. "Because the abdominal pain and tenderness may be severe, appendicitis or another acute condition requiring surgery may be the initial diagnosis."
More than anything, the CDC stresses that hospitals should screen all stool samples - bloody or not - for E. coli. "Although bloody stools are common with E. coli infection, the diagnosis must be considered in patients with non-bloody diarrhea as well," Boyce says.
A 1995 survey of 129 randomly selected clinical labs found that only 29% screened all stool samples for E. coli, though an additional 25% screened all bloody stool specimens for the bacteria. Those numbers, he says, must improve for outbreaks to be properly identified for the more severe cases of HUS to be quickly known.
Severity tied to high white cell counts
Treated or not, E. coli usually disappears in about a week, except in cases of HUS, which attacks about 6% of all patients and should be diagnosed from two to 14 days - with a mean of six days - after the onset of diarrhea. In children, of whom those ages 5 months to 6 years are most susceptible, HUS is characterized by hemolytic anemia, thrombocytopenia, renal failure, and central nervous system manifestations.
The CDC also reports that the severity of HUS can be tied to elevated white cell counts. Once HUS has taken hold, a quarter of all patients experience neurological complications including seizures or coma, 50% require dialysis, and up to 75% require red cell transfusions.
When it comes to diagnosing E. coli, Boyce reiterates that it won't show up in routine stool cultures and that cases of bloody or non-bloody diarrhea should be considered E. coli if the patient is in day care, a nursing home, or possibly has consumed undercooked ground beef or unpasteurized milk.
When it comes to treatment, options are even less clear in the absence of a proven therapy, leaving researchers more sure of what not to do. Antimotility agents are specifically contraindicated in patients with bloody diarrhea. Some studies have argued that antimotilities can lead to HUS in patients with E. coli. Studies also have made or debunked the argument that certain antimicrobials lead to HUS.
The CDC recommends that during the initial week of the onset of diarrhea, patients should be monitored for any signs of HUS, particularly high-risk pediatric or elderly patients, done by peripheral blood smears, blood counts, and urinalysis.
Treating HUS can entail strict fluid and electrolyte balance, dialysis, transfusions, and IV immune globulin therapy, although health officials say efficacies have not been proven. That really leaves identification, containment, and reporting as the most tangible ways to stem an outbreak, with patient histories, cluster detection, patient setting, exposure, and recent behaviors as the key areas of concern.
Investigational HUS drug
Begun in 1996 as a $1.3 million grant from the National Institutes of Health, a five-year multinational drug trial to counter the effects of pediatric HUS remains in the very early stages.
The drug is SYNSORB, from Canadian pharmaceutical SYNSORB Biotech. A mix of synthetic carbohydrates, the drug is designed to bind onto E. coli bacteria, neutralizing its harmful effects and then passing through a patient's system. The drug is mixed with soft food and given four times a day.
With a goal of 210 patients, to date only 30 have been designated officially for the double-blind studies. So far, the drug has been free of known side effects, according to researchers involved in the trials, but publishable results remain far in the future.
"There's no question that something like this is needed to treat HUS. Right now, there is nothing we can offer a child to stop the infection," says Phillip Tarr, MD, a pediatric gastrointestinal specialist at Children's Hospital in Seattle. The only treatments to stop its spread are dialysis, IV feeding, and other life support system efforts in hopes that the condition will subside.
Tarr saw the effects of HUS up close in 1993, when Children's Hospital dealt with 38 cases during that state's outbreak of E. coli. The outbreak was traced to undercooked beef at a Jack-in-the-Box fast food restaurant.
SYNSORB trials are under way in the U.S., Canada, Japan, and Argentina.
[For additional information, contact the Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333. Telephone: (404) 639-3311.]
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