Pelvic inflammatory disease (PID) continues to pose great risk to the reproductive health of women worldwide, with the long-term sequelae of infertility, ectopic pregnancy, and chronic pelvic pain. The etiology of PID is generally recognized to be polymicrobial, and includes the sexually transmitted organisms Neisseria gonorrhoeae and /or Chlamydia trachomatis in approximately one-half of cases. Organisms associated with bacterial vaginosis are recovered from the upper genital tract from the majority of women with acute PID, suggesting that anaerobic organisms play an essential role in the pathogenesis of PID. Despite these findings, the Centers for Disease Control and Preventions'recommended outpatient treatment regimen does not provide effective activity against anaerobic microorganisms, leading to concerns that failure to eradicate anaerobic organisms from the upper genital tract may affect the long-term treatment goals of protecting fertility and limiting ectopic pregnancy. Our hypothesis is that an antibiotic regimen that includes anaerobic coverage will more effectively clear anaerobic microorganisms from the endometrium in women with acute PID compared to a standard antibiotic regimen lacking effective anaerobic therapy against anerobes.
Our specific aims are to 1. Compare the clearance of anaerobic organisms from the endometrium between PID treatment regimens with and without anaerobic coverage, 2. Evaluate the role of Mycoplasma genitalium in the pathogenesis of acute PID, and 3. Determine the treatment response between antibiotic treatment regimens for acute PID with and without optimal anaerobic therapy. To accomplish our goals, we will conduct a randomized phase III clinical trial in women with acute PID, comparing the only recommended treatment regimen for acute PID (ceftriaxone and doxycycline) to this same regimen with the addition of a two-week course of metronidazole. Our primary outcome is clearance of anaerobic organisms from the endometrium following treatment. As the importance of anaerobic therapy in PID remains an important yet unanswered question, the proposed study will provide critical information that will assist clinicians in the selection of the most effective antibiotic treatment regimen for women with PID.

Public Health Relevance

Pelvic inflammatory disease (PID) continues to pose grave risk to women's fertility. Currently recommended antibiotic treatments only target some of the bacteria that commonly cause this infection. This study will determine which antibiotics best treat the common bacteria that cause PID, thereby reducing the risk of infertility that occurs following PID.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-MMT-M)
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University of Pittsburgh
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Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women. Front Cell Infect Microbiol 8:307
Zheng, Xiaojing; O'Connell, Catherine M; Zhong, Wujuan et al. (2018) Discovery of Blood Transcriptional Endotypes in Women with Pelvic Inflammatory Disease. J Immunol 200:2941-2956
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