Mid-outbreak, treatment found for deadly E. coli infections

An unusually lethal strain of the bacterium Escherichia coli has infected more than 1,500 in Germany, killing at least 16 people.

The current outbreak – traced back to contaminated fruits and vegetables – is caused by a rare E. coli strain called O104:H4. And scientists are at a loss to explain why it’s so virulent, and particularly in healthy young adult women.

In an attempt to avert anticipated deaths, doctors in the cities where the outbreak is centered have set up a spontaneous clinical trial for an experimental drug called eculizumab – sold as Soliris – recently listed as the world’s single most expensive drug.

While most E. coli strains are harmless, a distressingly high proportion of those infected with this this enterohemorrhagic E. coli (EHEC) suffer from hemolytic uremic syndrome (HUS) infection – a potentially lethal complication attacking the kidneys that can provoke comas, seizures, and stroke.

On Friday, Rolf Stahl of the Hamburg-Eppendorf University Hospital and Reinhard Brunkhorst of the German Society of Nephrology rolled out an emergency eculizumab treatment strategy to hospitals across the country.

The monoclonal antibody drug has been on the market since 2007 as a treatment for a rare immune system disorder paroxysmal nocturnal hemoglobinuria, which destroys red blood cells. A year’s treatment costs $409,500.

But just last week, a new study reported successful use of the drug in treating HUS. A toxin produced by EHEC activates ‘complement’ proteins, but overactivity can lead to tissue damage in the kidneys.

The team, led by Franz Schaefer of the Center for Pediatrics and Adolescent Medicine in Heidelberg, treated 3 EHEC-infected children with eculizumab – which blocked the complement proteins and improved the patients’ blood-cell counts and kidney function.

A few days after the paper was accepted for publication, HUS cases started appearing in northern Germany.

The drug’s manufacturer, Alexion, is now providing eculizumab free of charge in Germany, taking advantage of an unexpectedly large cohort of patients that might help to speed the drug’s approval for the treatment of HUS.

The drug costs at least €15,000 ($22,000) per patient.

“But we don’t want to be overly optimistic,” Brunkhorst cautions, “we have very little experience with this drug and don’t know how effective it will be.” And because this strain has never been implicated in an outbreak of human EHEC infections before, scientists are racing to sequence the strain’s DNA while doctors are figuring out how to save lives on the fly.

The Food and Drug Administration will conduct a 6-month ‘priority review’ of Soliris as a treatment for HUS. The agency usually takes 10 months to review drug candidates, but speeds up the process for conditions that don’t have good treatment options.

The study was published in the New England Journal of Medicine last week.