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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Taylor, Brandie D; Zheng, Xiaojing; Darville, Toni et al. (2017) Whole-Exome Sequencing to Identify Novel Biological Pathways Associated With Infertility After Pelvic Inflammatory Disease. Sex Transm Dis 44:35-41
Petrina, Melinda A B; Cosentino, Lisa A; Rabe, Lorna K et al. (2017) Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin. Anaerobe 47:115-119
Russell, Ali N; Zheng, Xiaojing; O'Connell, Catherine M et al. (2016) Identification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection. J Infect Dis 214:1884-1892
Russell, Ali N; Zheng, Xiaojing; O'Connell, Catherine M et al. (2016) Analysis of Factors Driving Incident and Ascending Infection and the Role of Serum Antibody in Chlamydia trachomatis Genital Tract Infection. J Infect Dis 213:523-31
Barral, Romina; Desai, Ruchi; Zheng, Xiaojing et al. (2014) Frequency of Chlamydia trachomatis-specific T cell interferon-? and interleukin-17 responses in CD4-enriched peripheral blood mononuclear cells of sexually active adolescent females. J Reprod Immunol 103:29-37
Darville, Toni; Pelvic Inflammatory Disease Workshop Proceedings Committee (2013) Pelvic inflammatory disease: identifying research gaps--proceedings of a workshop sponsored by Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases, November 3-4, 2011. Sex Transm Dis 40:761-7
Darville, Toni (2013) Recognition and treatment of chlamydial infections from birth to adolescence. Adv Exp Med Biol 764:109-22
Frazer, Lauren C; Scurlock, Amy M; Zurenski, Matthew A et al. (2013) IL-23 induces IL-22 and IL-17 production in response to Chlamydia muridarum genital tract infection, but the absence of these cytokines does not influence disease pathogenesis. Am J Reprod Immunol 70:472-84
Vicetti Miguel, Rodolfo D; Harvey, Stephen A K; LaFramboise, William A et al. (2013) Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity. PLoS One 8:e58565
Taylor, Brandie D; Darville, Toni; Ferrell, Robert E et al. (2013) Racial variation in toll-like receptor variants among women with pelvic inflammatory disease. J Infect Dis 207:940-6

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