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Study finds no benefit of antibiotics before miscarriage surgery
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Antibiotic prophylaxis for miscarriage surgery did not significantly lower the risk for pelvic infection during a double-blind, placebo-controlled, randomized clinical trial conducted in four low- or middle-income countries, according to findings published in The New England Journal of Medicine.
The trial actually produced divergent results depending on which criteria the researchers used to define a pelvic infection.
Initially, pelvic infection was defined using strict criteria based on CDC and WHO guidance, with a diagnosis requiring that patients have two or more of four listed clinical features — purulent vaginal discharge; pyrexia; uterine, parametrial, or adnexal tenderness; or leukocytosis.
“However, during the conduct of the trial, it was observed by the examining clinicians that for some patients, only a single feature of infection was present, but the symptoms were of sufficient severity that the clinicians judged that there was pelvic infection and that treatment was required,” David Lissauer, MBChB, PhD, from the University of Birmingham in England, and colleagues explained.
On this advice, Lissauer and colleagues changed the primary outcome to pelvic infection within 14 days after surgery as defined by the presence of one of the four clinical features, “or by the presence of one of these features and the clinically identified need to administer antibiotics.”
“There was concern that the original criteria, although highly specific, could lead to missed diagnoses in some patients with infection,” the researchers wrote. “This was potentially a patient safety issue, particularly where patient access to care was limited. Therefore, after discussion with the trial steering committee and the data and safety monitoring committee, it was decided that the diagnostic criteria by which pelvic infection was defined should be widened. The original strict definition of pelvic infection was reclassified as a secondary outcome. These changes were made before data were unblinded.”
The trial
According to Lissauer and colleagues, 208 million women and adolescents become pregnant each year globally, and 10% to 20% of these pregnancies end in spontaneous abortion.
“In many of these cases, surgery is needed to remove retained products of conception; such surgery is one of the most common gynecologic operations performed worldwide,” they wrote.
Infection is a serious potential consequence of these surgeries, especially in low- and middle-income countries.
“Rates of surgery for incomplete spontaneous abortion are high owing to low uptake of nonsurgical management approaches, a higher incidence of infections after surgery in these countries than in high-income countries, and poor access to resources to care for women in whom complications develop. High-quality evidence is needed for rational antimicrobial prescribing,” they wrote.
For the study, Lissauer and colleagues enrolled 3,412 patients in Malawi, Pakistan, Tanzania and Uganda, with 1,705 patients receiving a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole and 1,707 receiving placebo.
Using the broader criteria, the results showed that the risk for pelvic infection was 4.1% (68 of 1,676 pregnancies) in the antibiotics group and 5.3% (90 of 1,684 pregnancies) in the placebo group. According to the original strict criteria, pelvic infection was diagnosed in 1.5% (26 of 1,700 pregnancies) in the antibiotics group and 2.6% (44 of 1,704 pregnancies) in the placebo group.
“We found that antibiotic prophylaxis with doxycycline and metronidazole before miscarriage surgery did not result in a significantly lower 14-day risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. However, results suggested a possible benefit when pelvic infection was defined by strict criteria,” Lissauer and colleagues wrote.
Data provide ‘reasonable support’ for antibiotics
In an accompanying editorial, David M. Serwadda, MBChB, MPH, of the Makerere University School of Public Health in Kampala, Uganda, said the criteria that Lissauer and colleagues eventually used to determine the primary outcome “have important limitations” — namely, they did not provide “a clear definition of what constituted perceived need for antibiotics.”
“The change made in the definition of the primary outcome has major implications for the interpretation of the results. Whereas the original criteria would be expected to identify more severe and definitive cases of pelvic infection, the revised criteria would be expected to be more sensitive but less specific, by including women with mild or no pelvic infections,” he wrote.
Serwadda said changing the primary outcome to make it less specific “may have inadvertently reduced the probability of observing a true difference in event rates between the trial groups.”
“Thus, although the investigators concluded that antibiotic prophylaxis before miscarriage surgery ‘did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo’ I would interpret the results as indicating that antibiotic prophylaxis prevented pelvic infections as defined by international diagnostic criteria,” he wrote. “Given the risks associated with pelvic infections in [low- and middle-income countries], these data provide reasonable support for prescribing prophylactic antibiotics in these settings. Antibiotic resistance, however, will need to be monitored.” – by Caitlyn Stulpin
Disclosure: Lissauer reports receiving grant support paid from MSD for Mothers paid to the University of Birmingham. Please see the study for all other authors’ relevant financial disclosures. Serwadda reports no relevant financial disclosures.
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