Researchers note gain against stubborn infection

C. difficile infections have become more common and more severe in recent years as virulent strains have taken hold. It is the leading cause of hospital-acquired diarrhea, making its spread a growing concern.

Up to a third of people with C. difficile, mostly over 50, suffer recurring infections after being treated with antibiotics for the first infection.  Many patients have multiple recurrences. Scientists suspect that antibiotics destroy normal organisms in the digestive system, making people more vulnerable to new C. difficile infections or resurgence of the bacteria that persist despite antibiotics.

A team from MassBiologics, which is part of University of Massachusetts Medical School, and the New Jersey biotech company Medarex created monoclonal antibodies to fight C. difficile. From previous work, they knew that people who had recurrences had not formed their own antibodies in response to the initial infection, so they used genetic engineering to create human antibodies that would fight two toxins found in C. difficile.

In the new trial, the researchers randomly assigned 200 patients receiving standard antibiotics for C. difficile infections to receive either a single infusion of the monoclonal antibodies or a placebo. After 84 days, 7 of the 101 patients in the antibody group had a recurrence of the infection, compared with 25 of 99 patients in the placebo group.

"What's really critical here is that this is the first new therapy that is preventing recurrence of C. difficile," Ambrosino said in an interview. "There is nothing out there for patients, and this product, if it goes through licensure and gets to patients, will offer them an opportunity not to have that recurrence."

Lahey's Ricciardi noted that the cost of the therapy would need to be weighed against longer term outcomes than were addressed in the study, such as death or continued illness. From a public health perspective, he said, the therapy's value would increase if it both cured patients and made them unable to spread the bacteria to other people.

The next step is a larger trial of the therapy, whose ultimate cost is not known, Ambrosino said. MassBiologics and Medarex have sold the rights to commercialize the product to the pharmaceutical company Merck, which would carry out further trials and seek federal approval for the treatment.

MassBiologics, formerly called the Massachusetts Biological Laboratory,  develops new products that will have an impact on public health, Ambrosino said. The nonprofit arm of UMass is also working on monoclonal antibodies against hepatitis C and rabies.

Some authors of the New England Journal article work for Medarex or have equity interests in Medarex or Merck. Ambrosino is an inventor of the product, but said she does not have any financial gain from it.

"The trial results are impressive," Dr. Lorraine Kyne of University College, Dublin, writes in an editorial published with the article. "This novel nonantibiotic approach to secondary infection is likely to offer hope to physicians and patients battling C. difficile infection."