PARK CITY, UTAH – Adding metronidazole to ceftriaxone/doxycycline for acute pelvic inflammatory disease (PID) improved clearance of endometrial anaerobes and reduced the frequency of pelvic tenderness at 30 days, without reducing overall antibiotic compliance, in a randomized, placebo-controlled trial conducted at the University of Pittsburgh.
Anaerobic organisms are associated with endometritis, but guidelines from the Centers for Disease Control and Prevention have been equivocal about adding metronidazole to standard antibiotic regimens, citing a lack of data. CDC currently recommends treatment “with or without metronidazole.”
Dr. Harold Wiesenfeld
“Finally, we have data. This work has been needed to be done for over a decade. This is a huge contribution to the literature,” said Cheryl Walker, MD, of the department of obstetrics and gynecology at the University of California, Davis; she moderated the study presentation.
All 233 women in the study received ceftriaxone 250 mg (intramuscular) once and doxycycline 100 mg orally twice a day for 14 days; 116 were randomized to metronidazole 500 mg orally twice a day for 14 days, and 117 to matching placebo.
At 30 days, just 8% in the metronidazole group had pelvic tenderness, compared with 22.3% in the placebo arm (P = .006); clinical outcomes were otherwise similar.
Meanwhile, all of the women taking metronidazole cleared Atopobium vaginae, anaerobic gram-negative rods, and anaerobic gram-positive cocci, while one-third of women in the placebo group did not (P = .02).
Many clinicians hesitate to give metronidazole for PID out of concern that the drug’s gastrointestinal side effects will cause women to quit their antibiotic regimens early, but that wasn’t a problem in the Pittsburgh study. Compliance and adverse events were similar in both groups; 53.8% of the women taking metronidazole, for instance, versus 47.1% of women in the placebo arm, reported gastrointestinal side effects (P = .57).
“When we unmasked the treatment arms and showed there was really no difference, it was very surprising. When we looked at compliance at a level of 75% of drugs taken – we used blister packs and self-report – 90% of women in each arm took at least 75% of the medication,” Dr. Wiesenfeld said. Metronidazole side effects didn’t have much of an impact in the study, he added.
The women were a mean age of 23 years old; 59% were black, 28% were white, and 15% had private insurance. The groups were well balanced, with similar clinical presentations and prevalence of chlamydia (15%), gonorrhea (7%), Mycoplasma genitalium (18%), bacterial vaginosis (55%) and Trichomonas vaginalis (8.9%). Pregnant women and those requiring hospitalization were among those excluded from the study.
The work was funded by the National Institutes of Health. Hologic donated laboratory reagents. Dr. Wiesenfeld reported having no relevant disclosures.