ICAAC: Got Clostridium Difficile Diarrhea? Got Milk?

SAN FRANCISCO, Sept. 27 -- Immunogenically enhanced cow's milk may sharply reduce the relapsing diarrhea associated with Clostridium difficile infection, according to a study from Holland.

In an open-label, uncontrolled trial, the so-called MucoMilk cut the expected relapse rate in half in 107 C. difficile patients, found Jaap van Dissel, M.D., Ph.D., of the University of Leiden.

"The preliminary efficacy evidence shows about a 50% reduction in the relapse rate, although of course we still need a randomized controlled trial," Dr. van Dissel told the Interscience Conference on Antimicrobial Agents and Chemotherapy here.

Over the course of the study, he said, 10 of the 100 patients had a relapse after the milk therapy. By comparison, the relapse rate in a 2005 C. difficile outbreak in The Netherlands was 23%, Dr. van Dissel said.

Dr. van Dissel and colleagues used an enhanced milk product from the Leiden company Mucovax BV, which specializes in milk-based antibody therapies. The experimental milk was taken from cows immunized against C. difficile and its toxins and converted into a powder.

Reconstituted later, it was given to patients as a "medical food" after in vitro and animal studies showed it appeared to block the vicious cycle of C. difficile-associated diarrhea, Dr. Van Dissel said.

Because the cows are immunized against the pathogen, their milk contains high levels of secretory immunoglobulins that target C. difficile and the cytotoxins that cause associated diarrhea, Dr. van Dissel said, but the total level of immunoglobulins is the same as in normal milk.

For that reason, he said, there are few safety issues. "Normal milk also has immunoglobulins, people drink it, and it's safe," Dr. van Dissel said.

A small number of people - less than 5% -- stopped taking it because they didn't like the flavor, which is "like skimmed milk," Dr. van Dissel said.

Patients with serious underlying medical conditions were less likely to respond to the treatment, Dr. van Dissel said, as were those infected with the prevalent 027 strain that is linked to major outbreaks in Canada and in the U.S.

On the other hand, he reported the case of an 82-year-old man with chronic lymphocytic leukemia, who was on immunosuppressive medication and had suffered a spleen hemorrhage after trauma. The man had recurrent C. difficile diarrhea, which each time was treated successfully with antibiotics.

But after the third relapse, he was treated with Cipro (ciprofloxacin) for two weeks and then given the milk product for three weeks and has not had a relapse since, Dr. van Dissel said.

The difficulty with C. difficile-associated diarrhea is that the treatment itself sets up the body for relapse, commented Emilio Bouza, M.D., Ph.D., of the University of Madrid, who chaired the symposium at which Dr. Van Dissel spoke.

But "it's not just a problem of antibiotics, it's a problem of immunity," he said, and many researchers have tried ways to improve the immunity of C. difficile patients, including vaccines and passive immunotherapy.

The enhanced milk is "a very brilliant approach," Dr. Bouza said, limited by the fact that it can't be applied to the more serious cases, in which patients no longer can tolerate anything by mouth.

The study also showed that the effect did not depend on the ribotype/serotype of the C. difficile causing the infection, implying that it was likely mediated by specific sIgA antibodies against shared toxins.