May 26, 2021
By Manie Beheshti, MD
The role of anaerobic organisms in pelvic inflammatory disease (PID) is unclear. Anaerobes are frequently recovered from women with PID and can be destructive to the epithelium and the fallopian tubes. However, studies thus far have failed to demonstrate the benefits of the universal addition of metronidazole for all patients with PID. The 2015 guidelines from the Centers for Disease Control and Prevention reflect this by making the addition of metronidazole optional.
In the April 1 issue of Clinical Infectious Diseases, researchers report on the benefits of the addition of metronidazole for the treatment of PID. In this randomized, double-blind, placebo-controlled trial spanning more than 5 years, 117 women were treated with standard therapy: a single dose of intramuscular ceftriaxone 250 mg, 14 days of twice daily oral doxycycline 100 mg, and placebo. One hundred sixteen women were treated with ceftriaxone, doxycycline, and 14 days of twice daily metronidazole 500 mg. Both groups had comparable histories of chlamydia, gonorrhea, or PID. The rates of bacterial vaginosis, C. trachomatis, N. gonorrhoeae, M. genitalium, and T. vaginalis were similar between both treatment groups.
Clinical improvement at the 3-day follow-up visit was equivalent with an overall improvement of 91.3%. At the 30-day follow-up, while pelvic pain was similar between the two groups, there was a statistically significant difference in pelvic organ tenderness between the metronidazole group (9%) and the placebo group (20%). Recovery of anaerobic organisms from the endometrium was less common in the metronidazole group (8% vs 21%). Lastly, although often cited as a concern for including metronidazole in the therapeutic regimen, adherence and tolerability in both groups were similar.
Though the impact on fertility and long-term complications cannot be gleaned from these findings, this well-designed study points out the short-term benefits of including metronidazole in the standard outpatient regimen of women with PID. It also helps quell the concerns over issues with metronidazole’s adherence and tolerability. Yet, the answers this study provides highlight the many more unanswered questions. As noted in the accompanying editorial, this is an example of the underrepresentation of women’s health in research, and while this study is a “step forward ... we must do better.”