The Importance of Anti-anaerobic Therapy for Acute Pelvic Inflammatory Disease (PID)

This study is a randomized placebo-controlled trial comparing two antibiotic treatment
regimens for acute PID. Women with acute PID will be randomized to one of two treatment
regimens. One group of women will receive a single intramuscular dose of ceftriaxone 250 mg,
doxycycline 100 mg orally twice a day for 14 days, along with placebo tablets orally twice a
day for 14 days. The second group of women will receive the same doses of ceftriaxone and
doxycycline, and metronidazole 500 mg orally twice a day for 14 days. The primary objective
is to compare the eradication of anaerobic organisms from the upper genital tract in women
with acute PID who receive standard outpatient antibiotic treatment to the eradication of
these organisms from the upper genital tract in women who receive standard outpatient
treatment along with a two-week course of metronidazole. Women will be followed for one month
for clinical outcomes, and will undergo assessment for clearance of microorganisms from the
upper genital tract. Our hypothesis is that an antibiotic treatment regimen that includes
anaerobic coverage will more effectively clear anaerobic organisms from the endometrium in
women with acute PID compared to a standard antibiotic treatment regimen lacking effective
antibiotic coverage against anaerobes.

Inclusion Criteria:

Women must meet all of the following inclusion criteria:

1. Age 15-40 at the time of enrollment (Note: Participants between the ages of 15-17 will
require written informed consent from parent/legal guardian. Written assent will also
be obtained from the minor)

2. Acute PID, defined by symptoms and signs guided by current CDC guidelines:50

1. Current symptoms of lower abdominal or pelvic pain (present for ≤30 days) AND

2. Cervical motion tenderness AND/OR uterine tenderness AND/OR adnexal tenderness on
pelvic examination

3. Ability to provide written informed consent

Exclusion Criteria:

Women with any of the following will be ineligible to participate:

1. Pregnant or nursing a baby (Note: a urine pregnancy test will be done at enrollment.
Result must be negative to participate in the study.)

2. Uterine procedure (e.g. dilation and curettage, abortion) or miscarriage within the
past 6 weeks.

3. Allergy to any of the study medications (cephalosporins, doxycycline, or
metronidazole) or Type 1 hypersensitivity allergic reaction to penicillin for those
with unknown tolerance to cephalosporins.

4. Systemic or vaginal antibiotic therapy in the preceding 7 days

5. Requires inpatient PID therapy (per the current CDC guidelines)50

6. Inability to obtain an endometrial biopsy at enrollment

7. Known inability to comply with the follow-up visits

8. Prior hysterectomy

9. Menopause (including natural menopause defined as lack of menses for 12 consecutive
months [in the absence of pregnancy] and surgical menopause defined as a woman who has
had both ovaries removed)

10. Inability to swallow pills

11. Not willing to refrain from alcohol during the two week treatment period (and two
additional days following completion of study medication)

12. Other condition present at enrollment that requires additional antibiotic treatment

13. Current use of any of the following medications:

- Anticoagulants, coumarin- or indandione-derivative: warfarin

- cimetidine (Tagamet)

- Disulfiram

- Seizure medications including: phenytoin (Dilantin), carbamezapine (Tegretol),
barbiturates (i.e. Phenobarbital)

- Lithium

- Immunosuppressive drugs including: cyclosporine, amprenavir

- Antacids, minerals or bismuth subsalicylate (Pepto Bismol)

14. Any condition, in the opinion of the investigator that would interfere with the
participant's safety or with study outcomes

15. Participation in any study involving an investigational product in the past 30 days or
anticipation of participation in any study using an investigational product in the
next 30 days

16. Previous participation in this study

17. Evidence of a tuboovarian abscess