Toxic Shock Syndrome After Medical Abortion
Abstract & Commentary
By Leon Speroff, MD
Professor of Obstetrics and Gynecology, Oregon Health and Sciences University, Portland
Dr. Speroff is a consultant for Barr Laboratories.
Synopsis: Rare cases of fatal toxic shock syndrome associated with Clostridium sordellii have been reported; clinicians are urged to be aware of warning signals.
Source: Fischer M, et al. Fatal Toxic Shock Syndrome Associated with Clostridium sordellii After Medical Abortion. N Engl J Med. 2005;353:2352-2360.
The CDC reported 4 cases of fatal Toxic Shock Syndrome in California associated with Clostridium sordellii that occurred within one week after medical abortions (induced with 200 mg of oral mifepristone and 800 µg of vaginal misoprostol).1
Patient 1: A healthy 18-year-old woman underwent medical abortion at 47 days gestation and, 4 days later, was seen in an emergency ward with abdominal cramping. She was afebrile and there was no tenderness on physical examination. No laboratory studies or cultures were obtained. Three days later, the patient returned with nausea, vomiting, and weakness. She was again afebrile, but now had tachycardia, hypotension, an extremely elevated white count, blood cultures that later were negative, and bilateral infiltrates on chest X-ray. She still had no positive findings on physical examination. Despite treatment with antibiotics, the patient rapidly developed respiratory distress and died 10 hours after admission.
Patient 2: A healthy 21-year-old woman underwent medical abortion at 43 days gestation, and became unresponsive 6 days later. Resuscitation was unsuccessful. No laboratory studies or cultures were performed.
Patient 3: A healthy 22-year-old woman underwent medical abortion at 53 days gestation, and presented to an emergency ward 5 days later with nausea, vomiting, diarrhea, and abdominal pain. The patient had normal vital signs except for mild tachycardia. The patient was admitted to rule out an ectopic pregnancy, and the next day developed hypotension, diffuse abdominal tenderness, a white count of 120,200 cells/µL, and metabolic acidosis. Blood cultures before antibiotic treatment were negative. Within a few hours, the patient had a cardiopulmonary arrest. Emergency laparotomy revealed a large amount of serous peritoneal fluid that failed to grow aerobic or anaerobic bacteria. The patient died during surgery, 23 hours after coming to the hospital.
Patient 4: This healthy 34-year-old woman had her medical abortion at 45 days gestation, and presented to an emergency ward 4 days later with nausea, vomiting, and abdominal pain. Vital signs were normal, and the only finding on physical examination was abdominal tenderness. Her white count was elevated and cultures of blood and urine were later negative. Despite antibiotic treatment, the patient went into refractory hypotension and died 12 hours after presenting to the hospital.
The autopsies revealed pleural, pericardial, and peritoneal effusions, inflammation of endometrium and myometrium with multiple small abscesses, necrosis, and hemorrhage without gas formation. There were no retained fetal or placental tissues. Formalin-fixed tissues were obtained by the CDC, and Clostridium sordellii was identified in uterine tissues by a nonspecific polyclonal anti-clostridium antibody, followed by specific polymerase-chain-reaction assays on extracted DNA.
Commentary
Clostridium sordellii is a Gram-positive anaerobic bacillus that has been previously identified as a cause of fatal toxic shock syndrome in 10 cases in the United States, 8 within one week after delivery of live-born infants, one within a week after a medical abortion, and one not associated with pregnancy (and one more case in Canada following medical abortion). The clinical and pathological findings (responses to exotoxins) in the 4 new cases and the 10 previous cases were similar. Clostridium species are known to colonize the vagina and to be associated with postpartum endometritis and septic abortion. Recognized infections with Clostridium sordellii, however, are very rare, although this rare prevalence may be partly due to the difficulty in the isolation and identification of this organism. The usual anaerobic culture techniques seem to be insufficient for timely diagnosis. The FDA has reported that testing the manufacturing lots of mifepristone and misoprostol has indicated no evidence of bacterial contamination.
How great is the risk? The 4 patients in this report and the one previous case (whose death was attributed to a ruptured ectopic pregnancy) represent the only fatal cases recognized after nearly 500,000 uses of medical abortion in the United States since mifepristone was approved in 2000. The mortality rate is estimated to be from 1.0 to 1.5 per 100,000, a rate that would be higher than that associated with legal surgical abortions. The number of American women reported as dying from abortion declined from nearly 300 deaths in 1961, to only 6 in 1985, 10 in 1992, and 4 in 1999, or about 0.6 deaths for every 100,000 legal abortions.2,3 The risk of death from any cause associated with pregnancy is higher. For comparison, in 1990, the maternal death rate for childbirth in the United States was 10 per 100,000 births, and for ectopic pregnancy, approximately 50 per 100,000 cases4-6 and, in 1992, 17 deaths were associated with spontaneous miscarriage.2
Why haven’t similar cases been reported in Europe? Philip Darney has speculated regarding the possibilities.7 Because of equivalent efficacy and safety, the currently accepted method of medical abortion, supported by the recommendation of the World Health Organization, uses 200 mg mifepristone orally followed the next day by 800 µg misoprostol vaginally; this differs from the FDA-approved regimen of 600 mg mifepristone orally followed by 400 µg misoprostol also given orally. Thus, one might suspect different American and European experiences to reflect the different dose of mifepristone; however, American clinicians have not followed the FDA-approved regimen, but instead, used the European lower-dose regimen that has solid clinical trial support. The use of self-administered vaginal misoprostol in America is different compared with the European practice of administering misoprostol by health care personnel in a clinic setting. Darney questions whether the misoprostol oral route, with its equivalent pharmacokinetic behavior, might be preferable.
Is there an alteration in immunity secondary to one of the drugs. McGregor and Equiles suggest that mifepristone may impair stress responses by blocking both progesterone and glucocorticoid receptors.8 On the other hand, Grimes points out that infection with Clostridium sordellii has occurred without exposure to mifepristone.9
At this point in time, no changes have been suggested in the regimen used for medical abortion. The best prevention of fatal toxic shock with this rare infection is awareness of the possibility and early recognition. Abdominal cramping as a presenting complaint makes the diagnosis difficult because this is a common symptom following medical abortion. Unique characteristics include: the absence of fever, markedly elevated white counts, fluid effusions sufficient to produce hemoconcentration, and eventually tachycardia and hypotension. Specific antibiotics with demonstrated efficacy against Clostridium sordellii have not been identified. Early recognition of this rare infection would mandate consideration of aggressive surgery with hysterectomy, a lesson learned from the experience with septic abortions in the years before legalized abortion.
References
- Fischer M, et al. Fatal Toxic Shock Syndrome Associated with Clostridium sordellii After Medical Abortion. N Engl J Med. 2005;353:2352-2360.
- Koonin LM, et al. Centers for Disease Control Abortion Surveillance: United States, 1996. MMWR. 1999;48:1-42.
- Elam-Evans LD, et al. Abortion surveillance-United States, 2000. MMWR. 2003;52:1-32.
- Lawson HW, et al. Abortion Mortality, United States, 1972 Through 1987. Am J Obstet Gynecol. 1994;171:1365-1372.
- Lawson HW, et al. Ectopic Pregnancy Surveillance, United States, 1970-1986. MMWR. 1989;38:11.
- Berg CJ, et al. Pregnancy-Related Mortality in the United States, 1987-1990. Obstet Gynecol. 1996;88:161-167.
- Darney PD. Deaths Associated with Medication Abortion. Contraception. 2005;72:319.
- McGregor JA, Equiles O. Risks of Mifepristone Abortion in Context. Contraception. 2005;72:393.
- Grimes DA. Response Letter to the Editor. Contraception. 2005;72:394.
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