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New Treatment for PID – Should We Add Metronidazole?

May 10, 2021

Written by Graham Van Schaik

Spoon Feed
Adding metronidazole to the current IDSA regimen of ceftriaxone (CTX) and doxycycline for outpatient pelvic inflammatory disease (PID) treatment is generally well tolerated and associated with less-frequent recovery of anaerobic organisms and improved clinical response compared to CTX and doxy. 

Why does this matter?
PID is a spectrum of disease that, left untreated, can predispose women to chronic pelvic pain, ectopic pregnancy, abscess formation, sepsis, and infertility. Previous research has found an association between the presence of anaerobic organisms following treatment of pelvic infections and subsequent infectious morbidity when anti-anaerobic therapy has not been administered. These authors sought to identify:

  1. Primarily – if adding metronidazole to IDSA recommended outpatient treatment led to a clinical improvement at a 3-day follow up;

  2. Secondarily – if anaerobes could be isolated in the endometrium at 30 days following treatment.

Next time you treat a patient with PID why not cef-TRI-axone doxy-nidazole….
This was a randomized, double-blind, placebo-controlled trial that compared current IDSA PID guidelines (a single IM shot of 250mg CTX [now 500mg] and doxy 100mg BID for 14 days) to current treatment PLUS metronidazole 500mg BID or a matching placebo for 14 days. They enrolled a total of 233 women over a 4+ year period at an academic ED and county health STD clinic in Pittsburgh, PA. The researchers followed these women for 30 days, checking a clinical pain score at time of enrollment, 3 days following treatment, and a clinical cure (as defined by >70% improvement in tenderness score) at the 30-day mark. They also measured the presence of anaerobic organisms in the endometrium at 30 days following treatment.

There was no difference in the primary outcome of clinical improvement at day 3. While only 184 (79%) women continued all the study medication (taking >75% of prescribed medication), patients taking metronidazole were less likely to have pelvic organ tenderness a month after enrollment than those who received placebo (9% vs 20%, P=0.037). They also found that BV and Trich were more effectively treated, and the metronidazole group had fewer follow-up endometrial cultures positive for anaerobes (8% vs 21%, P< .05). Lastly, there was no significant difference in adverse events (89.7% vs 80.3%, P = .07), though the metronidazole group did have a higher rate of vulvovaginal candidiasis (15.5% vs 6%, P=.02).  GI complaints were similar among the two groups.

Overall, this study, while small in total sample size, supports the routine use of metronidazole with CTX and doxy for the treatment of women with PID and should serve to inform future treatment guidelines.

A Randomized Controlled Trial of Ceftriaxone and Doxycycline, With or Without Metronidazole, for the Treatment of Acute Pelvic Inflammatory Disease. Clinical Infectious Diseases, 2020 72(7), 1181–1189. https://doi.org/10.1093/cid/ciaa101

What are your thoughts?