What causes Pelvic Inflammatory Disease (PID) in women of reproductive age?

What Causes Pelvic Inflammatory Disease (PID)

PID is caused by ascending infection from the cervix to the upper genital tract, most commonly by the sexually transmitted organisms Neisseria gonorrhoeae and Chlamydia trachomatis, along with polymicrobial involvement of anaerobic and aerobic bacteria from the vaginal flora. 1

Primary Causative Organisms

Sexually Transmitted Pathogens

• Neisseria gonorrhoeae and Chlamydia trachomatis are the most important sexually transmitted organisms causing PID, with cervical isolation rates ranging from 27-80% for gonorrhea and 5-39% for chlamydia in women diagnosed with PID 1
• Between 10-40% of women with untreated gonococcal or chlamydial cervicitis develop clinical symptoms of acute PID 1
• Mycoplasma genitalium has recently been implicated as an additional sexually transmitted cause of acute PID 2

Endogenous Vaginal Flora

• A wide variety of anaerobic and aerobic bacteria from the vaginal flora are isolated from the upper genital tracts of 25-50% of women with acute PID 1
• The most common anaerobic bacteria include Bacteroides species (particularly Bacteroides fragilis), Peptostreptococcus, and Peptococcus species 1
• Common facultative bacteria include Gardnerella vaginalis, Streptococcus species, Escherichia coli, and Haemophilus influenzae 1
• Bacterial vaginosis (BV) has been identified as an antecedent condition that leads to polymicrobial acute PID, with organisms involved in BV being similar to those isolated from the upper genital tract 1

Other Organisms

• Mycoplasma hominis and Ureaplasma urealyticum may be etiologic agents in some cases, though their role is less clearly defined 1
• Cytomegalovirus (CMV) may occasionally cause PID 1

Pathogenesis and Mechanism of Infection

Route of Spread

• PID results from direct canalicular (ascending) spread of organisms from the endocervix through the endometrium to the fallopian tube mucosa and peritoneum 1
• Noncanalicular spread via parametrial lymphatics has also been observed 1

Contributing Factors to Ascending Infection

• Uterine instrumentation (such as IUD insertion) facilitates upward spread of vaginal and cervical bacteria 1
• Hormonal changes during menses and menstruation itself lead to cervical alterations that result in loss of the mechanical barrier preventing ascent 1
• The bacteriostatic effect of cervical mucus is lowest at the onset of menses 1
• Retrograde menstruation may favor ascent of organisms to the tubes and peritoneum 1
• Individual organisms possess virulence factors associated with pathogenesis of acute chlamydial and gonococcal PID 1

Clinical Context and Polymicrobial Nature

• Most cases of PID are associated with more than one organism, making it a polymicrobial infection 1, 2
• The proportion of women infected with specific organisms varies widely based on population characteristics, time intervals, severity of infection, and diagnostic methods used 1
• Even when N. gonorrhoeae or C. trachomatis are not isolated, treatment must still cover these organisms because negative endocervical screening does not preclude upper reproductive tract infection 1

Important Clinical Pitfall

A critical caveat is that ceftriaxone and other cephalosporins have no activity against Chlamydia trachomatis, so when treating PID where chlamydia is a suspected pathogen, appropriate antichlamydial coverage (such as doxycycline or azithromycin) must be added 3. This is why empiric treatment regimens for PID always include coverage for both gonorrhea and chlamydia, along with anaerobic bacteria 1, 4.