Clinical Trial for the Treatment of Pelvic Inflammatory Disease Shows Efficacy of Combination Therapy Using Metronidazole

Researchers from the Department of Obstetrics, Gynecology, and Reproductive Sciences at UPMC Magee-Womens Hospital, led by principal investigator Harold Wiesenfeld, MD, published promising findings from their single-center, randomized controlled trial that investigated the efficacy and tolerability of metronidazole when added to the Centers for Disease Control and Prevention (CDC) recommended regimen of ceftriaxone and doxycycline for the treatment of pelvic inflammatory disease. Results from the clinical trial were published in the journal Clinical Infectious Diseases in February. 

Clinical Trial Summary and Aims

This study (NCT01160640), launched in 2010, was a randomized placebo-controlled trial comparing two antibiotic treatment regimens for acute pelvic inflammatory disease (PID). Women with acute PID were randomized into one of two treatment regimens. The first cohort received a single intramuscular dose of ceftriaxone (250 mg), and doxycycline (100 mg orally twice a day for 14 days), along with placebo tablets taken orally twice a day for 14 days. The second study cohort received identical doses of ceftriaxone and doxycycline, but with the addition of metronidazole (500 mg orally twice a day for 14 days). 

The primary objective of the study was to compare the presence of anaerobic organisms in the upper genital tract in women with acute PID following standard outpatient antibiotic treatment to the presence of these organisms in women after receiving the standard outpatient treatment along with a two-week course of metronidazole.
The study followed the two cohorts of women for one month to ascertain clinical outcomes. Each group was assessed for anaerobic microorganisms from the upper genital tract prior to and after completion of antibiotic therapy. 

“Our hypothesis at the beginning of the study was that an antibiotic treatment regimen that includes anaerobic coverage would more effectively clear anaerobic organisms from the endometrium in women with acute PID compared to the standard antibiotic treatment regimen lacking effective antibiotic coverage against anaerobes,” says Dr. Wiesenfeld.

Key Findings and Clinical Implications

A total of 233 women were enrolled in the study. One hundred sixteen were included in the cohort who received metronidazole, and 117 in the placebo group.

In addition to measuring the clinical improvement in the study participants at the three-day point after treatment, the study gathered data on 30-day outcomes, including clinical improvement or cure, the presence of anaerobic bacteria in the endometrium, and the study participants tolerance of metronidazole and their adherence to the prescribed regimen. Clinical cure for the purposes of this study was defined as no fever and an absence or reduction in the experience of tenderness in the pelvic region.

To summarize the key findings, while the level of clinical improvement between the two cohorts was similar at the three-day assessment, measurable improvements in the presence of anaerobic bacteria were seen in the metronidazole group. Eight percent of those receiving metronidazole had detectable levels of anaerobic organisms, while 21% in the placebo group showed positive findings.

The presence of Mycoplasma genitalium, an organism currently under investigation as a possible cause of PID, was detectable in cervical samples in 4% of individuals receiving metronidazole versus 14% in the placebo group. There were no discernible differences in adverse events or treatment regimen adherence between the two groups.

The incidence of pelvic tenderness at the 30-day follow-up was less frequent in the metronidazole group (9%) compared to those receiving the placebo (20%).

“From our study, it appears to be clear that adding metronidazole to the standard of care treatment for PID can improve outcomes, with little or no drawbacks. More work likely needs to be done to better understand the effects of varying doses and other factors. Still, we are confident that clinicians ought to consider adding metronidazole to the CDC-recommended therapy of ceftriaxone and doxycycline for PID," says Dr. Wiesenfeld.

Collaborators in the clinical trial included Sharon Hillier, PhD, and Leslie A Meyn, PhD, from the Department of Obstetrics, Gynecology, and Reproductive Sciences; Toni Darville, MD, from the Department of Pediatrics; and Ingrid Macio, PA-C, from the Magee-Womens Research Institute.

Reference

Wiesenfeld HC, Meyn LA, Darville T, Macio IS, Hillier SL. A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease. Clin Infect Dis. 2020 Feb 13; ciaa101. Epub ahead of print.

More About Dr. Wiesenfeld

Harold Wiesenfeld, MD, is professor of obstetrics and gynecology, vice chair for gynecologic services, and director of the Division of Gynecologic Specialties and the division of Reproductive Infectious Diseases. Dr. Wiesenfeld is active on both the research and clinic fronts with a range of studies in progress aimed at improving treatments and testing for conditions such as pelvic inflammatory disease and sexually transmitted diseases.

Since 1996, Dr. Wiesenfeld has operated the Vaginitis and Vulvar Disorders Clinic at UPMC Magee-Womens Hospital, one of only a few centers in the country to offer a multidisciplinary referral clinic for women with reproductive infectious diseases and vulvar disorders, providing treatment and counseling for vulvar disorders and for complicated, complex, or recurrent vaginal infections and STDs.