Pelvic Inflammatory Disease (PID) is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and/or ovaries. It is typically an ascending infection, spreading from the lower genital tract. The majority of cases of PID are related to a sexually transmitted infection. The diagnosis of PID is primarily clinical and should be suspected in female patients with lower abdominal or pelvic pain and genital tract tenderness. During the patient’s evaluation, other etiologies of pain including ectopic pregnancy should be considered and ruled out. PID is treated with antibiotics to cover the primary pathogens including Neisseria gonorrhoeae and Chlamydia trachomatis. Short-term complications include tubo-ovarian or pelvic abscess. Long-term complications include ectopic pregnancy, infertility, and chronic pelvic pain. Early diagnosis and treatment can potentially prevent complications.

Causes of Pelvic Inflammatory Disease

Ascending infection from the cervix causes PID. In 85% of cases, the infection is caused by sexually transmitted bacteria. Of the offending agents, the bacteria Neisseria gonorrhoeae or Chlamydia trachomatis are the most common pathogens. Approximately 10% to 15% of women with endocervical N. gonorrhea or C. trachomatis will go on to develop PID. Typically, gonorrheal PID is more severe than PID due to other causes. PID due to chlamydia is less likely to cause symptoms, and therefore, more likely to result in subclinical PID. Subclinical PID can produce little to no symptoms, but can still have adverse long-term consequences.

Other cervical microbes, including Mycoplasma genitalium, have been thought to contribute to the disease. Additionally, pathogens responsible for bacterial vaginosis (Peptostreptococcus species, Bacteroides species), respiratory pathogens (Haemophilus influenza, Streptococcus pneumonia, Staphylococcus aureus), and enteric pathogens (Escherichia coli, Bacteroides fragilis, group B Streptococci) have been implicated in acute PID, and account for approximately 15% of cases overall.

Chlamydia trachomatis and Neisseria gonorrhoeae are usually the main cause of PID. Data suggest that PID is often polymicrobial.[rx] Isolated anaerobes and facultative microorganisms have been obtained from the upper genital tract. N. gonorrhoeae has been isolated from fallopian tubes, facultative and anaerobic organisms were recovered from endometrial tissues.[rx][rx]

The anatomical structure of the internal organs and tissues of the female reproductive tract provides a pathway for pathogens to ascend from the vagina to the pelvic cavity through the infundibulum. The disturbance of the naturally occurring vaginal microbiota associated with bacterial vaginosis increases the risk of PID.[rx]

N. gonorrhea and C. trachomatis are the most common organisms. The least common were infections caused exclusively by anaerobes and facultative organisms. Anaerobes and facultative bacteria were also isolated from 50 percent of the patients from whom Chlamydia and Neisseria were recovered; thus, anaerobes and facultative bacteria were present in the upper genital tract of nearly two-thirds of the PID patients.[rx] PCR and serological tests have associated extremely fastidious organisms with endometritis, PID, and tubal factor infertility. Microorganisms associated with PID are listed below.[rx] Rarely cases of PID have developed in people who have stated they have never had sex.[rx]

Bacteria

  • Chlamydia trachomatis
  • Neisseria gonorrhoeae
  • Prevotella spp.
  • Streptococcus pyogenes
  • Prevotella Livia
  • Prevotella designs
  • Bacteroides spp.
  • Peptostreptococcus saccharolytic
  • Peptostreptococcus anaerobic
  • Gardnerella vaginalis
  • Escherichia coli
  • Group B streptococcus
  • α-hemolytic streptococcus
  • Coagulase-negative staphylococcus
  • Atopobium vaginae
  • Acinetobacter spp.
  • Dialister spp.
  • Fusobacterium gonidiaformans
  • Gemella spp.
  • Leptotrichia sp.
  • Mogibacterium spp.
  • Porphyromonas spp.
  • Sphingomonas sp.
  • Veillonella spp.
  • Cutibacterium acnes
  • Mycoplasma genitalium[rx][rx]
  • Mycoplasma hominis
  • Ureaplasma spp.[rx]
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Symptoms of Pelvic Inflammatory Disease

Symptoms in PID range from none to severe. If there are symptoms, then fever, cervical motion tenderness, lower abdominal pain, new or different discharge, painful intercourse, uterine tenderness, adnexal tenderness, or irregular menstruation may be noted.[rx][rx][rx][rx]

Possible symptoms include:

  • pain, possibly severe, especially in the pelvic area
  • fever
  • fatigue
  • bleeding or spotting between periods
  • irregular menstruation
  • pain in the lower back and the rectum
  • pain during sexual intercourse
  • unusual vaginal discharge
  • frequent urination
  • vomiting

Other complications include endometritis, salpingitis, tubal-ovarian abscess, pelvic peritonitis, periappendicitis, and perihepatitis.[rx]

Diagnosis of Pelvic Inflammatory Disease

Endometrial biopsy is rarely done if there is a doubt about the diagnosis. The biopsy usually shows the presence of inflammation but the organism is never identified.

History and Physical

  • Women with PID may present with lower abdominal or pelvic pain, vaginal discharge, dyspareunia, and/or abnormal vaginal bleeding.  Therefore, PID should be suspected in any young female presenting with lower abdominal pain and pelvic discomfort.
  • Risk factors include intercourse with multiple partners, age, previous history of PID, intrauterine device implantation, and tubal ligation. As PID is primarily a clinical diagnosis, a thorough history, and physical exam is crucial. Clarification of the onset and character of the pain should be obtained, while also exploring possible alternative diagnoses.
  • All women with suspected PID should have a pelvic examination to evaluate for cervical discharge, cervical motion tenderness, uterine tenderness, adnexal tenderness, or masses. The diagnosis of pelvic inflammatory disease is clinical and is defined by lower genital tract inflammation such as cervical discharge, an increased number of white blood cells on wet prep, or cervical friability.

Evaluation

  • Laboratory evaluation – should include a pregnancy test to exclude the possibility of an ectopic pregnancy as an alternate etiology of pelvic pain. Additionally, practitioners should consider microscopy of vaginal or cervical discharge (if present) along with nucleic acid amplification tests (NAAT) for C. trachomatis and N. gonorrhea. Testing for other sexually transmitted infections like HIV and Treponema pallidum (syphilis) should be considered as well. Additionally, if there is a concern for a turbo-ovarian abscess, pelvic ultrasound should be considered.
  • Nucleic acid amplification tests (NAATs) – direct fluorescein tests (DFA), and enzyme-linked immunosorbent assays (ELISA) are highly sensitive tests that can identify specific pathogens present. Serology testing for antibodies is not as useful since the presence of the microorganisms in healthy people can confound interpreting the antibody titer levels, although antibody levels can indicate whether an infection is recent or long-term.[rx]
  • Pelvic and vaginal ultrasounds –  are helpful in the diagnosis of PID. In the early stages of infection, the ultrasound may appear normal. As the disease progresses, nonspecific findings can include free pelvic fluid, endometrial thickening, uterine cavity distension by fluid or gas. In some instances, the borders of the uterus and ovaries appear indistinct. Enlarged ovaries accompanied by increased numbers of small cysts correlates with PID.[rx]

Treatment of Pelvic Inflammatory Disease

As stated before, the diagnosis of pelvic inflammatory disease is primarily clinical. PID should be considered in any sexually active young woman with pelvic or low abdominal pain and evidence of genital tract tenderness on exam. While laboratory tests may help confirm the diagnosis, NAAT testing typically can take several hours to days to result depending on your institution. Negative results do not exclude the diagnosis. An ultrasound or CT without findings of PID does not exclude the diagnosis. Therefore, early and prompt treatment should be started based on clinical suspicion.

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Indications for hospitalization include pregnancy, failed outpatient treatment, severe clinical illness, PID with pelvic abscess, or the possible need for surgical intervention.

Empiric treatment for PID in the inpatient setting includes:

  • Cefotetan (2 g intravenously [IV] every 12 hours) plus doxycycline (100 mg by mouth every 12 hours) or
  • Cefoxitin (2 g IV every 6 hours) plus doxycycline (100 mg by mouth every 12 hours) or
  • Clindamycin (900 mg IV every 8 hours) plus gentamicin (3 to 5 mg/kg IV once daily)

The CDC recommends the following for first-line treatment for outpatient therapy:

  • Doxycycline (100 mg orally twice a day for 2 weeks) plus ceftriaxone 250 mg intramuscularly (IM) for one dose or cefoxitin 2 g IM with probenecid (1g orally) for one dose or another parenteral third-generation cephalosporin

Metronidazole (500 mg orally twice per day for 14 days) should be added if there is a concern for trichomonas or recent vaginal instrumentation.

PID antibiotic regimens per 2015 CDC PID treatment guidelines

Parenteral treatment
Regimen A CeFotetan 2 g IV every 12 hours + doxycycline 100 mg PO or IV every 12 hours
Regimen B CeFoxitin 2 g IV every 6 hours + doxycycline 100 mg PO or IV every 12 hours
Regimen C Clindamycin 900 mg IV every 8 hours + gentamicin 2 mg/kg loading dose IV or IM followed by 1.5 mg/kg every 8 hours (can substitute single daily dosage of 3–5 mg/kg)
Alternate regimen Ampicillin/sulbactam 3 g IV every 6 hours + doxycycline 100 mg orally or IV every 12 hours
Oral treatment
Regimen A CeFtriaxone 250 mg IM in a single dose + doxycycline 100 mg PO BID for 14 days ± metronidazole 500 mg PO BID for 14 days
Regimen B CeFoxitin 2 g IM and probenecid 1 g PO in a single dose + doxycycline 100 mg PO BID for 14 days ± metronidazole 500 mg PO BID for 14 days
Regimen C A Third-generation cephalosporin + doxycycline 100 mg PO BID for 14 days ± metronidazole 500 mg PO BID for 14 days

Notes: Reproduced from CDC. 2015 Sexually Transmitted Diseases Treatment Guidelines. Atlanta, GA: Department of Health and Human Services; 2015. Trials have shown short-term clinical effectiveness with monotherapy azithromycin 500 mg IV daily for one or two doses +250 mg PO for 5–6 days or combined with a 12-day course of metronidazole.,

The reported efficacy of CDC-recommended treatment regimens for inpatient and outpatient management of PID

TnQTable % Response to treatment References
Inpatient
Cefotetan 2g IV q12h AND 89–94% [, ]
Doxycycline 100mg PO/IV q12h
followed by Doxycycline 100mg PO BID for a total of 14 days
Cefoxitin 2g IV q6h AND 84–95% [, –]
Doxycycline 100mg PO/IV q12h
followed by Doxycycline 100mg PO BID for a total of 14 days
Clindamycin 900mg IV q8h AND 84–90% [, , ]
Gentamicin 2mg/kg IV/IM load then 1.5 mg/kg maintenance
OR 3–5mg/kg daily dosing
Followed by Doxycycline 100mg PO BID OR
Clindamycin 450mg PO QID, total 14-day course
Ampicillin/Sulbactam 3g IV q6h AND 85–94% [, ]
Doxycycline 100mg PO/IV q12h
Followed by Doxycycline 100mg PO BID, total 14 day course
Outpatient
Ceftriaxone 250mg IM once AND 72–95% [, , ]
Doxycycline 100mg PO BID, total 14 days;
Cefoxitin 2mg IM once, with Probenecid 1g PO once AND 90% []
Doxycycline 100mg PO BID, total 14 days;
Other parenteral third-generation cephalosporins (cefotaxime, ceftizoxime) AND –
Doxycycline 100mg PO BID, total 14 days
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Equivalent oral and IV bioavailability for doxycycline. IV doxycycline causes burning, therefore elect for oral doxycycline if able to be tolerated
Must add clindamycin 450mg PO QID or metronidazole 500mg PO q6h in the setting of a tube-ovarian abscess, for a total 14-day course
Continue clindamycin in the setting of tubo-ovarian abscess
The higher-end of the range is a regimen including metronidazole
or all three regimens, consider adding metronidazole 500mg PO BID for 7 days

Complications

Delayed treatment of PID has a strong association with worsened outcomes and long-term complications. However, even with timely treatment, long-term complications can occur. One study estimated that for females with PID between 20 to 24 years of age, 18% would eventually develop chronic pain, 8.5% would develop ectopic pregnancies, and 16.8% would struggle with infertility.

Chronic pelvic pain is seen in as many as one-third of women with PID. The pain is thought to be related to inflammation, scarring, and adhesions from the infectious process. The strongest predictor of developing chronic pelvic pain related to PID is recurrent PID.

Infertility can also result from PID, regardless if the patient is symptomatic or asymptomatic from the pelvic infection. The infection can cause severe damage to the fallopian tubes, including loss of the ciliary epithelial cells of the fallopian tube and occlusion of the tube. The effects on fertility can be pronounced, with some studies indicating a 5-fold increase in infertility in women with a history of PID. Infertility related to PID is more likely to occur if chlamydia is the infectious cause, if there is a delay in treatment for PID, if the patient has recurrent episodes of PID, or if the case of PID is more severe.

The increased risk for ectopic pregnancy following PID is also related to damage to the fallopian tubes. In one study the rate of ectopic pregnancy following PID is approximately 7.8% according to one study, while the non-PID ectopic rate is 1.3%.

Prevention

Regular testing for sexually transmitted infections is encouraged for prevention. The risk of contracting the pelvic inflammatory disease can be reduced by the following:

  • Using barrier methods such as condoms; see human sexual behavior for other listings.
  • Seeking medical attention if you are experiencing symptoms of PID.[rx]
  • Using hormonal combined contraceptive pills also helps in reducing the chances of PID by thickening the cervical mucosal plug & hence preventing the ascent of causative organisms from the lower genital tract.[rx]
  • Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.[rx]
  • Getting an STI history from your current partner and strongly encouraging them to be tested and treated before intercourse.[rx]
  • Diligence in avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.[rx]
  • Reducing the number of sexual partners.[rx]
  • Sexual monogamy.[rx]
  • Abstinence[rx]

References

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