On the Fly, German Doctors Find Treatment for Deadly E. coli Infections

In the middle of the biggest outbreak of food poisoning caused by the bacterium enterohemorrhagic Escherichia coli (EHEC) that Germany has ever seen, a group of doctors may have found a way to treat the most severe cases. The finding appears today in The New England Journal of Medicine (NEJM).

At least four people have died in the outbreak, thought to have been caused by eating contaminated vegetables. To date, 276 patients have developed hemolytic uremic syndrome (HUS). The potentially fatal syndrome, characterized by a destruction of red blood cells and severe kidney problems caused by the bacteria’s toxin, is the most severe complication of an EHEC infection.

In the article, Franz Schaefer, a nephrologist at the Center for Pediatrics and Adolescent Medicine in Heidelberg, Germany, and other physicians describe how they successfully treated three EHEC-infected children suffering from HUS with a novel approach. They used the monoclonal antibody eculizumab, which has been on the market since 2007, to treat a rare blood disorder. Eculizumab inhibits a part of the human immune system called the complement system that usually destroys invading cells that have been tagged for destruction by other parts of the immune system.

The complement system has been implicated for some time in certain patients who develop HUS without any EHEC infection, known as atypical HUS patients, and eculizumab has been used successfully to treat them. Recent research suggests that the complement system might also be involved in the HUS cases caused by EHEC.

Last autumn, Schaefer saw a young girl suffering from HUS due to an EHEC infection. He first tried the most common treatment, replacing the patients’ blood plasma with donor plasma to rid the body of the toxins. (HUS patients are usually not treated with antibiotics because the antibiotics can aggravate the symptoms by releasing the shiga toxin from the bacteria in large amounts.)

When the girl’s health did not improve, Schaefer tried the antibody. "We did not have any other option. She was showing severe neurological symptoms, paralysis of one side of the body, cramps, and then slipped into a coma," Schaefer remembers. “But when we finally gave her the antibody, she improved immensely within 24 hours,” Schaefer says. “This was not a controlled experiment, of course,” he says. “But the improvements were very suggestive of being due to the treatment.”

Schaefer was apparently not the only one with this idea. When he wrote a case report for NEJM, the editors notified him that two other groups had sent in similar reports around the same time. “So we wrote something all together and it was accepted for publication 14 days ago,“ Schaefer says. A few days later, HUS cases started appearing en masse in northern Germany.

“I could not believe it," Schaefer says. "HUS cases with severe neurological symptoms are very rare, but now they are everywhere." He also informed his colleagues elsewhere. “A lot of them have asked about the new treatment, and a few patients are already being treated with it."

At the university clinic in Essen, Andreas Kribben is treating two HUS patients with the antibody. "We have seven HUS patients altogether, but we are using eculizumab only on the two patients that are not responding to the plasmapheresis," he says. Kribben wrote the original paper on using eculizumab to treat atypical HUS, so he had experience with the drug. “We actually started treating the first patient on Wednesday, before Schaefer’s paper came out. Sadly, we have not seen the kind of response that Schaefer describes and that we know from the atypical HUS patients," he says.

Jens Nürnberger, nephrologist at a clinic in Schwerin is somewhat skeptical of the treatment. “There is no real evidence for this treatment," he says. “It might work or it might not." The cases described in Schaefer’s paper could also be spontaneous remissions, he cautions. "The other problem is that this drug is hugely expensive, costing at least €15000 per patient, and the health insurance is not going to pay for it.“

However, in cases in which no other option remains, doctors would be right to try the new drug anyway, Nürnberger says. “But we should really be defining groups of patients who will get the drug and groups who do not and make this into a kind of controlled study," he says. “Instead, a lot of people will be treated this way, some will get better, some will not. In the end, we will not have learned anything.“ But he, like everyone else, is still hoping that this will turn out to be the right treatment at the right time.