What is the etiology of Pelvic Inflammatory Disease (PID) in sexually active women of reproductive age?

Etiology of Pelvic Inflammatory Disease

PID is a polymicrobial infection primarily caused by sexually transmitted organisms—most commonly Neisseria gonorrhoeae and Chlamydia trachomatis—along with various anaerobic and aerobic bacteria that ascend from the lower genital tract to the upper reproductive organs. 1, 2

Primary Causative Organisms

Sexually Transmitted Pathogens

• Chlamydia trachomatis is recovered from the cervix in 5-39% of women diagnosed with PID, with serologic evidence found in 20-40% of women with PID history 3, 1
• Neisseria gonorrhoeae shows wide variation in isolation rates, recovered from the cervix in 27-80% of PID cases and from fallopian tubes in 13-18% of cases 3, 2
• Mycoplasma genitalium has been implicated as a causative organism, though its precise role remains less clearly defined than chlamydia and gonorrhea 3, 4

Polymicrobial Flora

• Anaerobic bacteria are isolated from the upper genital tract in 25-50% of acute PID cases, most commonly Bacteroides, Peptostreptococcus, and Peptococcus species 3, 2
• Aerobic/facultative bacteria frequently involved include Gardnerella vaginalis, Streptococcus species, Escherichia coli, and Haemophilus influenzae 3
• Bacterial vaginosis (BV) serves as an antecedent condition, with BV-associated organisms contributing to polymicrobial PID through similar bacterial profiles found in both conditions 3, 5

Pathogenesis and Mechanism of Spread

Route of Infection

• Direct canalicular spread is the primary mechanism, with organisms ascending from the endocervix through the endometrium to the fallopian tube mucosa 3, 1, 5
• Noncanalicular spread via parametrial lymphatics has also been documented as an alternative pathway 3, 5

Progression from Lower to Upper Tract

• 10-40% of women with untreated gonococcal or chlamydial cervicitis develop clinical symptoms of acute PID, though even higher percentages show subclinical endometritis on endometrial biopsy 3, 2, 5
• The progression represents an infectious continuum from cervicitis to endometritis to salpingitis and potentially to peritonitis 4

Contributing Factors to Ascending Infection

Mechanical and Procedural Factors

• Uterine instrumentation, particularly intrauterine device (IUD) insertion, facilitates upward spread of vaginal and cervical bacteria into the upper genital tract 3, 2, 5

Hormonal and Physiologic Factors

• Hormonal changes during menstruation alter the cervical mucus barrier, with bacteriostatic effects at their lowest at menses onset 3, 5
• Retrograde menstruation may carry organisms from the lower to upper genital tract 3, 5
• Loss of mechanical cervical barrier during menses facilitates bacterial ascent 3

Organism-Specific Factors

• Individual virulence factors of specific organisms influence the likelihood and severity of ascending infection 3, 5

Clinical Context and Diagnostic Considerations

Pathogen-Negative PID

• Approximately 62% of clinically diagnosed PID cases may have no detectable chlamydia, gonorrhea, M. genitalium, or BV, representing either false-positive diagnosis, PID from other microbiological causes, or cleared cervical infection 6
• These pathogen-negative cases are more likely in women aged ≥30 years, with less vaginal inflammation and less reported unprotected sex 6

Silent or Subclinical Disease

• Many women experience minimal or no symptoms ("silent PID"), yet still develop serious sequelae including tubal infertility 3, 5
• High rates of PID sequelae occur in women with serologic evidence of previous STIs but no history of overt illness 3

Common Pitfalls to Avoid

• Do not assume PID is monoinfectious—most cases involve multiple organisms requiring broad-spectrum coverage 2, 7
• Do not wait for positive STI testing to treat—clinical diagnosis based on pelvic organ tenderness should prompt empiric therapy, as cervical sampling may miss upper tract pathogens 1, 4
• Do not overlook BV as a contributing factor—screen for and treat BV-associated organisms as part of the polymicrobial etiology 3, 5
• Do not dismiss mild symptoms—abnormal discharge, metrorrhagia, postcoital bleeding, and urinary frequency may represent PID even without fever or severe pain 4