ATLANTA — While the precise nature of the link between medical abortion and fatal toxic shock-like syndrome remains a mystery, the handful of case reports have prompted a difference in opinion about how such procedures should be carried out.
Activists have responded to the reports by calling for a removal of mifepristone (Mifeprex) from the U.S. market. Planned Parenthood, in contrast, has not stopped using mifepristone but has called for an end to the use of intravaginal misoprostol following oral mifepristone. This regimen is not approved by the Food and Drug Administration but is widely used and was associated with all five of the reported fatal Clostridium sordellii infections following medical abortion in the United States and Canada.
For its part, the American College of Obstetricians and Gynecologists will review the final report of the FDA panel before issuing any statements, Dr. Kevin Ault said in an interview.
Five cases of fatal C. sordellii infection have been reported against a background of approximately 560,000 medical abortions a year. “None of it is common. Clearly there are cases related to pregnancy that have nothing to do with pregnancy termination, and then there is the smaller group of nonpregnant cases. It's hard to find cause and effect here,” Dr. Ault said in an interview following a 1-day meeting on emerging clostridial disease sponsored by the Centers for Disease Control and Prevention that he attended on behalf of ACOG.
At the meeting, researchers discussed the latest information in order to draft a research agenda for C. sordellii and C. difficile, another emerging infection associated with toxin-mediated sepsis that has also affected pregnant women.
Dr. Marc Fischer, a medical epidemiologist at the CDC, summarized the published literature to date on infections involving C. sordellii, a gram-positive anaerobic bacillus that resides in soil and colonizes the gastrointestinal and/or genital tracts of healthy humans. In various case reports and series, the organism has been identified in cases of pneumonia, endocarditis, arthritis, peritonitis, corneal ulcer, and bacteremia, and in wound infections among patients with necrotizing fasciitis, tissue allograft infections, neonatal omphalitis, postpartum endometritis, and episiotomy infections.
Between 1977 and 2001, C. sordellii genital tract infections and toxic shock-like syndrome were reported in 10 women, among whom the preceding events were childbirth (8) and medical abortion (1), reported from Canada in 2001. Another four cases were identified between 2003 and 2005, all involving women who had undergone medical abortions using the common “off-label” regimen of 200 mg oral mifepristone followed by 800 mcg vaginal misoprostol, said Dr. Fischer, who was the lead author of the published report of those four cases (N. Engl. J. Med. 2005;353:2352–60).
The four recent cases were all previously healthy women from California who developed symptoms including tachycardia, hypotension, vomiting or diarrhea, and abdominal pain within 5 days of taking mifepristone. Clinical laboratory findings in three of the patients included leukemoid reaction in all three, hemoconcentration in two, and thrombocytopenia in two. All died within a day of hospitalization. The clinical and pathologic findings in these cases were similar to those of the 10 previously reported cases, Dr. Fischer said.
Dr. L. Clifford McDonald, also of the CDC, reported that three additional cases of fatal toxic shock-like syndrome following medical abortion are currently under investigation by the CDC. Each of these differs in various ways from the previous five: One, in a woman who had taken oral mifepristone followed by vaginal misoprostol, was associated with C. perfringens, not C. sordellii. A second case, also of C. perfringens, involved the use of misoprostol with the cervical dilator Laminaria, not mifepristone. The third, although initially reported as being associated with a medical abortion, could not be confirmed as such. Moreover, investigation has shown pathologic findings consistent with appendicitis, serositis, and pneumonia, he noted.
Meanwhile, there have been three reported cases of toxic shock-like syndrome following spontaneous abortion, all involving C. sordellii. One of these patients was coinfected with C. perfringens. Another patient, in whom the C. sordellii did not possess the genes encoding the lethal toxin, was the only one who survived.
Several speakers offered hypotheses as to the mechanism for the lethal infections. Dr. James A. McGregor, of the obstetrics and gynecology department at Keck School of Medicine, Los Angeles, noted that mifepristone is a potent inhibitor of both progesterone and glucocorticoid receptors. As such, mifepristone may impair host immune responses and predispose women to lethal infections caused by toxigenic C. sordellii and other pathogens that exist normally in low numbers in the reproductive tracts of many women (Contraception 2005;72:393).