Two New Fatalities from Clostridium sordellii, Neither Linked to Morning-After Pill

BOISE, Idaho, Nov. 7 -- Two more fatalities from the rarely encountered pathogen Clostridium sordellii have been reported, neither linked to the so-called morning-after pills, Mifeprex (mifepristone) and Cytotec (misoprostol), according to investigators here.

The new cases involved a four-year-old boy after a closed transverse fracture on his arm and a 21-year-old women after a normal birth of a child during which she had a third-degree vaginal laceration, , reported Michael Aldape, Ph.D., of the Veteran's Affairs Medical Center here.

These two patients brought to 45 the reported cases of Clostridium sordellii infections in the world's literature from 1927 to 2006, according to a review paper on the pathogen Dr. Aldape and colleagues published in the Dec. 1 issue of Clinical Infectious Diseases.

They found that 69% of patients died, usually within two to six days of developing the infection.

For reasons that the review suggested could not be unraveled with currently available data, five American women who had a medically induced abortion with Mifeprex and Cytotec developed toxic shock and died because of a C. sordellii infection.

Those five cases account for 11% of the 43 found in the literature and two reported by Dr. Aldape and colleagues:

• Eight (or 18%) were associated with normal childbirth and two (or 0.4%) were associated with spontaneous abortion. The fatality rate was 100% in these groups and among those who were infected after a medically induced abortion.
• Ten (or 22%) infections occurred in injection drug users, and half died.
• Nineteen other cases of C. sordellii infection (or 43%) occurred after trauma or surgery, mostly in healthy people, and 53% died.

Last year, in response to reports of deaths associated with the use of Mifeprex and Cytotec, the FDA amended the product labeling to alert physicians.

"While there have been a handful of C. sordellii-related deaths stemming from mifepristone/misoprostol usage in the past few years, I believe the problem is more global," Dr. Aldape said. "There are many examples of non-gynecological infections due to C. sordellii in the literature, of which more than half were fatal."

The problem, the researchers said, is that diagnosis of C. sordellii is "confounded by early, nonspecific signs and symptoms and by the absence of fever." By the time physicians are aware of the possibility, it may be too late - especially since there is no rapid diagnostic test for the pathogen.

Characteristically, patients with a C. sordellii infection will develop a profound systemic capillary leak, refractory hypotension, and a marked leukemoid reaction, the researchers said, often followed rapidly by fatal tachycardia.

"In fact, the time between onset of symptoms and death is often so short that little time exists to initiate empirical anti-microbial therapy," Dr. Aldape and colleagues said.

There is little or no information on appropriate treatment, they said, adding that there is some evidence that the pathogen, like most of its cousins, is susceptible to ?-lactams, clindamycin, tetracycline, and chloramphenicol but is resistant to aminoglycosides and sulfonamides.

In an accompanying editorial, Beverly Winikoff, M.D., of Gynuity Health Projects, a New York-based research organization, said several theories have been put forward to explain why the infection might be associated with medically induced abortion, but none is convincing.

For example, Dr. Winikoff said, one idea was that Mifeprex suppressed the immune system in the five women who died, rendering them unable to battle the infection. But the drug has been used widely in Europe since 1988 - at a dose triple that used in the U.S. - and there have been no cases of associated C. sordellii infection reported there.

Also, the women who died after normal childbirth or a spontaneous abortion did not receive the drug, she noted.

Another possible explanation - since ruled out - was that the medication had been contaminated with C. sordellii.

"The importance of articles like (the review) is to point out that C. sordellii infections are a broader problem," she said. "It's a big intellectual and strategic error to focus on medical abortions. This is an infectious diseases issue."

But while researchers try to figure out the causes and treatment of C. sordellii infection, Dr. Aldape said, doctors should suspect the pathogen in patients who present within two to seven days after an injury, surgical procedure, drug injection, childbirth, or medically induced abortion and who complain of pain, nausea, vomiting, and diarrhea but have no fever.