Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI
Dr. Allen reports she receives grant/research support from Bayer and is a consultant for Merck.
SYNOPSIS: In this randomized, controlled trial of more than 3,000 women in developing countries with incomplete or missed abortion at less than 22 weeks’ gestation, antibiotic prophylaxis prior to uterine evacuation reduced infection rates when a strict definition for pelvic infection was used, but not when a more expanded definition was used.
SOURCE: Lissauer D, Wilson A, Hewitt CA, et al. A randomized trial of prophylactic antibiotics for miscarriage surgery. N Engl J Med 2019;380:1012-1021.
This was a randomized, controlled trial conducted in Malawi (three hospitals), Pakistan (five hospitals), Tanzania (three hospitals), and Uganda (two hospitals) comparing doxycycline 400 mg plus metronidazole 400 mg to placebo two hours prior to surgical evacuation of the uterus for spontaneous abortion (incomplete or missed abortion) at less than 22 weeks’ gestation. The surgery was conducted according to local practice and could include manual vacuum aspiration, suction curettage, or sharp curettage. Exclusion criteria included evidence of induced abortion, current pelvic infection, need for immediate surgery, current or recent (within seven days) antibiotic use, age younger than 16 years, or other contraindications to doxycycline and metronidazole. The primary outcome was pelvic infection within 14 days after surgery. The investigators studied two definitions for pelvic infection: 1) strict criteria requiring the presence of two or more of four clinical features — purulent vaginal discharge; fever > 38.0º C; uterine, parametrial, or adnexal tenderness on exam; and a white cell count of more than 12 × 109 per liter; and 2) expanded criteria that allowed the diagnosis of pelvic infection with only the presence of one criteria but with symptoms of sufficient severity that the clinician judged treatment was required.
A total of 3,412 women were randomized between June 2014 and April 2017. After withdrawals, 1,700 patients in the antibiotic prophylaxis group and 1,704 in the placebo group were included in the intention-to-treat analysis. Sharp curettage was used for 70% of the procedures, 23.2% manual vacuum aspiration, and 6.2% suction curettage. The majority of the cases (83%) were incomplete abortions. There was no difference between the two groups in terms of age, gestational age, HIV status, and socioeconomic indicators. The rate of pelvic infection with the strict criteria was 1.5% in the antibiotic group and 2.6% in the placebo group (relative risk [RR], 0.60; 95% confidence interval [CI], 0.37-0.96). The rate of pelvic infection with the expanded criteria was 4.1% in the antibiotic group and 5.3% in the placebo group (RR, 0.77; 95% CI, 0.56-1.04). There were no significant interactions according to maternal age, gestational age, HIV infection status, type of miscarriage, country of recruitment, timing of antibiotic prophylaxis, or residence in an urban or rural location. The only factor that affected the results was the type of surgery where the effect of the antibiotics appeared greater with manual vacuum aspiration (rate of infection, 1.3% antibiotic group vs. 4.1% placebo group; RR, 0.32; 95% CI, 0.12-0.86) than with sharp curettage (rate of infection, 5.3% antibiotic group vs. 6.0% placebo group; RR, 0.89; 95% CI, 0.64-1.23).
Antibiotic prophylaxis for surgically induced abortion has been the standard of care for many years based on strong evidence.1,2 However, recommendations for antibiotic prophylaxis for uterine evacuation for the indication of incomplete or missed abortion are inconsistent, mainly because of the lack of adequate trials. Extrapolating from induced abortion data, most providers do administer antibiotics prior to surgery, which aligns with the American College of Obstetricians and Gynecologists’ (ACOG) recommendations.2-4 It is unclear why the same procedure would have different risks of infection depending on the indication. One might theorize that women with early pregnancy loss are more likely to have known partners and, thus, have a lower risk of sexually transmitted infections. However, this has not been studied. The antibiotic regimen recommended by ACOG is 200 mg of doxycycline at least one hour preoperatively; however, other agents, such as azithromycin and metronidazole, have been used.2,4 Therefore, Lissauer et al intended to study, with sufficient sample size, the utility of antibiotic prophylaxis in low-resource countries, given that there is a higher incidence of infections after surgery in these countries compared to high-income countries and that women may not be able to access postoperative care if they develop complications.
The findings of this study are difficult to interpret because of the two definitions of pelvic infection used. The expanded criteria were instituted mid-trial because study clinicians were concerned that potential infections were missed in women who had only one sign of clinical infection. Therefore, the investigators decided to broaden the definition of pelvic infection. Now, there is evidence showing reduced infections with antibiotics when the strict definition of pelvic infection was used and no difference when the wider criteria were used. Looking at the data further, antibiotics made more of a difference compared to sharp curettage among women undergoing manual vacuum aspiration. Given that manual vacuum aspiration and suction curettage are practiced in the United States for uterine evacuation, as opposed to sharp curettage, this result is more relevant to U.S. practice. ACOG does not recommend the practice of sharp curettage alone for uterine evacuation, but it still is used widely internationally.3
One other aspect of this study that differs from U.S. practice is the high proportion of incomplete abortions (roughly 80%) treated compared to missed abortions. Therefore, the results may not be generalizable to the United States since the proportion of incomplete to missed abortions likely is reversed. U.S. providers treat many more women with missed abortions compared to incomplete abortions. It is unknown if this would change the results, although the investigators did not find the type of miscarriage to affect the findings. These investigators used two antibiotics and a higher dose of doxycycline than normally is used in the United States. Interestingly, there was no difference in vomiting (1.1% vs. 1.3%) and diarrhea (1.2% vs. 1.3%) between the two groups. My takeaway from this trial is that antibiotic prophylaxis for uterine evacuation for early pregnancy loss still is beneficial in the United States. The intervention is not expensive, if 200 mg of doxycycline is used, and has few side effects.
- Low N, Mueller M, Van Vliet HA, Kapp N. Perioperative antibiotics to prevent infection after first-trimester abortion. Cochrane Database Syst Rev 2012;(3):CD005217.
- Achilles SL, Reeves MF; Society of Family Planning. Prevention of infection after induced abortion: Release date October 2010: SFP guideline 20102. Contraception 2011;83:295-309.
- ACOG Practice Bulletin No. 200. Early Pregnancy Loss. American College of Obstetricians and Gynecologists. 2018.
- ACOG Practice Bulletin #195. Prevention of Infection After Gynecologic Procedures. American College of Obstetricians and Gynecologists. 2018.