Rare Fatal Toxic Shock Reported Following Medical Abortions

The four previously healthy women, ages 18 to 34, died from toxic shock syndrome caused by infection with Clostridium sordellii, following abortions induced with oral Mifeprex (mifepristone, RU-486) and vaginal misoprostol.

The women all died within a day of presenting to the hospital, investigators at the CDC here and health departments in California reported in the Dec. 1 issue of The New England Journal of Medicine.

None of the women when first seen had symptoms that would raise alarms. For example, they had no fevers or rashes and no evidence on autopsy of retained products of conception that might have served as a source of systemic infections. In addition, the women presented initially with abdominal pain or cramping, which occur commonly after medical and surgical abortions.

But for all four patients the conditions progressed rapidly to fulminant infections, and they all died remarkably rapidly, despite a lack of signs pointing to systemic infections, reported Marc Fischer, M.D., M.P.H., of the CDC and colleagues.

"The clinical and pathological findings in these cases are similar to those in 10 other cases of C. sordellii infection of the genital tract reported in the literature," they wrote. "Of the 10 previous cases that we identified, all occurred in previously healthy young women, and nine occurred within one week after delivery (eight women) or after abortion (one woman).

The investigators noted that initial symptoms of toxic shock associated with C. sordellii infection could be mistaken for side effects of misoprostol, such as vomiting, diarrhea, and abdominal cramping.

"To improve diagnosis and therapy, clinicians should be aware of the distinctive features of this potentially fatal entity, including tachycardia, hypotension, edema, hemoconcentration, profound leukocytosis, and absence of fever," the investigators wrote. "Health care providers should report to their state or local health department any cases of toxic shock syndrome occurring after an abortion or associated with pregnancy."

In an accompanying editorial, Michael F. Greene, M.D., of Harvard and an associate editor of the NEJM, noted that such infections are rare occurrences, and cautioned against misinterpretation of the findings.

"As tragic as the deaths of these young, healthy women are, they remain a small number of rare events without a clear pathophysiologic link to the method of termination," he wrote.

"Patients should be informed of this risk before they consent to the procedure and should be vigilant for symptoms after the procedure," Dr. Greene added. "Providers must be aware of this potential complication and not be reassured by the absence of fever. Regulators should keep this rare complication in perspective and not overreact to scant data by prematurely foreclosing the only approved medical option for pregnancy termination."

He estimated that the risk of death from infection following the use of the Mifeprex/misoprostol combination, also known as "the abortion pill," is less than one in 100,000. According to the CDC, from 1991 to 1999, the overall pregnancy-related mortality ratio in the U.S. was 11.8 deaths per 100,000 live births, ranging from 10.3 in 1991 to 13.2 in 1999.

C. sordellii infections occur infrequently in humans, and bacteremia and sepsis caused by the organism are rare. The Gram-negative anaerobic bacillus has, however, been reported to have caused some cases of pneumonia, endocarditis, arthritis, myonecrosis, and peritonitis, Dr. Fischer and colleagues wrote.

"There are limited data regarding the optimal therapy for C. sordelli toxic shock syndrome," Dr. Fischer and colleagues noted. "As with other severe histotoxic clostridial infections, aggressive surgical wound débridement, removal of infected organs (e.g., by means of hysterectomy), and antibacterial agents with good anaerobic activity are logical first steps to decrease the bacterial load and minimize further production of toxins."

In laboratory testing, C. sordellii has been demonstrated to be sensitive to antimicrobials such as penicillin, ampicillin, erythromycin, rifampin, tetracycline, cefoxitin, clindamycin, and metronidazole. In addition, bacterial protein synthesis inhibitors such as clindamycin may also be effective, the authors wrote.

"However, débridement, surgery, and antibacterial therapy will not mitigate the effects of preformed toxin," they added. "There are no clinical data on the use of immunoglobulin or anti-lethal toxin antibodies for treatment of C. sordellii infections."