Antibiotic prophylaxis did not significantly lower the risk of pelvic infection in low- and middle-income countries when administered before miscarriage surgery, according to a double-blind placebo-controlled randomized trial (AIMS Current Controlled Trials #ISRCTN97143849) published in The New England Journal of Medicine.
Patients from Malawi, Pakistan, Tanzania, and Uganda were enrolled, 1705 of whom were assigned to receive a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole; 1707 patients received identical placebos. The primary study outcome was pelvic infection within 14 days of surgery.
The risk of pelvic infection in the antibiotics and placebo groups was 4.1% (68/1676) pregnancies and 5.3% (90/1684 pregnancies, respectively (risk ratio [RR], 0.77; 95% CI, 0.56 to 1.04; P =.09) when a pragmatic infection criteria was applied. Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) in the antibiotics group and 2.6% (44 of 1704 pregnancies) in the placebo group (RR, 0.60; 95% CI, 0.37 to 0.96). There were also no significant differences in adverse events between groups.
At the beginning of the trial, the study investigators diagnosed infections using strict criteria based on guidance from the Centers for Disease Control and Prevention and the World Health Organization, a review of outcomes in existing trials of pelvic infection, and consensus among members of the international investigator group. Researchers then widened the criteria in advance of the unblinding of the data because of safety concerns that some infections were being missed. The updated criteria included clinician judgment, which researchers noted is likely to improve the sensitivity for identifying pelvic infections but also to decrease specificity. Further, they posited that adding clinician judgment to the definition, “is likely to have diluted the observed treatment effect, with the change in criteria adding 42 events to the antibiotic-prophylaxis group and 46 events to the placebo group.”
The study investigators concluded that antibiotic prophylaxis with doxycycline and metronidazole before miscarriage surgery did not result in a significantly lower 14-day risk of pelvic infection when defined using the pragmatic criteria. However, in the secondary analysis using strict criteria the results suggested a possible benefit, but investigators cautioned that, “we did not adjust for multiple comparisons of secondary outcomes.”
Lissauer D, Wilson A, Hewitt CA, et al. A randomized trial of prophylactic antibiotics for miscarriage surgery. New Engl J Med. 2019;380:1012-1021.