Obstetrics and Gynecology

Pelvic Inflammatory Disease (PID)

Pelvic Inflammatory Disease

1. What every clinician should know

Pelvic inflammatory disease (PID) is characterized as an upper genital tract infection in women that is associated with serious sequelae. PID results from the spread of microbes from the vagina through the cervix into the uterus, fallopian tubes, and peritoneal cavity. It represents a spectrum of infections which may include endometritis, salpingitis, oophoritis, pelvic peritonitis, tubo-ovarian abscess, and perihepatitis. Although PID is most often polymicrobial, specific organisms commonly associated with cervicitis and upper genital tract infection includes: Neisseria gonorrhoeae, Chlamydia trachomatis,Trichomonas vaginalis, and Mycoplasma genitalium.

PID can present in an acute or subclinical state. Acute PID is most often associated with severe abdominal or pelvic pain. Other symptoms include vaginal discharge, dyspareunia, dysmenorrhea, dysfunctional uterine bleeding, postcoital bleeding, dysuria, low back pain, nausea and vomiting, and fever. Patients with ruptured tubo-ovarian abscesses may appear septic and require immediate medical attention. Patients with subclinical PID are more well-appearing and may have vague symptoms.

Risk factors associated with PID include:

1. sexual activity, especially with multiple partners

2. a history of sexually transmitted infections (STIs)

3. lack of barrier contraceptive use

4. concurrent vaginitis, such as BV

5. intercourse during menstruation

6. tobacco use

7. gynecologic procedures involving cervical dilation

8. douching

2. Diagnosis and differential diagnosis

Diagnosis

PID is a clinical diagnosis and other morbid conditions (i.e. appendicitis) must be excluded when evaluating the patient. PID is diagnosed based on history and clinical exam. According to CDC recommendations, patients presenting with symptoms suggestive of PID, risk factors for STIs, and pelvic organ tenderness on exam should be treated empirically due to the sequelae of untreated infection. The diagnosis of PID according to clinical criteria is confirmed with diagnostic laparoscopy in approximately 65% of patients, so the sensitivity of these criteria is low. However, in order to capture more mild-moderate (subclinical) cases, it is prudent to treat empirically.

There are major and minor criteria to aid the clinician in making the diagnosis. Any one of the three major criteria along with clinical suspicion (abdominal or pelvic pain with risk of STIs) should be considered for empiric therapy.

The major criteria include: 1) uterine tenderness, 2) cervical motion tenderness (CMT), and 3) adnexal tenderness.

Minor criteria may increase the clinician's suspicion and improve the specificity of exam findings for the diagnosis of PID. These include: fever >101°F, leukocytosis, leukorrhea on microscopy of vaginal fluid, and elevated erythorcyte sedimentation rate (ESR) or elevated C-reactive protein.

A pelvic exam should be performed to determine if pelvic organ tenderness is present. The clinician should inspect the cervix for mucopus or friability. A nucleic acid amplification test (NAAT) for gonorrhea and Chlamydia should be collected. Vaginal fluid should be collected for microscopy (wet mount) and inspected for leukorrhea, bacterial vaginosis, and Trichomonas. All patients diagnosed with acute PID should be screened for HIV infection.

If a pelvic mass is detected on pelvic exam, it is advisable to order a transvaginal pelvic ultrasound to rule out tubo-ovarian abscess, which is present in approximately 30% of patients admitted for PID. The gold standard for diagnosis remains diagnostic laparoscopy, but this is not feasible or necessary in many settings. In patients in whom appendicitis is suspected, computed tomography (CT) of the abdomen-pelvis should be ordered.

Endometritis can be confirmed by obtaining an endometrial biopsy for histology and culture. This diagnostic tool has been used in reach but is not necessary for the clinical diagnosis and management of PID.

Differential Diagnosis

  1. Cervicitis (lower genital tract infection): Patients with cervicitis will not have pelvic organ tenderness on bimanual exam.

  2. Appendicitis: In order to exclude appendicitis, a CT scan of the abdomen and pelvis can be ordered.

  3. Ovarian Torsion: Ovarian torision is also a diagnosis of exclusion and based on history and physical exam. If the patient's history is suggestive of ovarian torsion and this cannot be excluded, it is best to proceed with a diagnostic laparoscopy in order to avoid loss of the affected adnexa.

  4. Ruptured Ovarian Cyst or Hemorrhagic Corpus Luteum: A pelvic ultrasound may help to differentiate PID from a ruptured ovarian cyst, but these may be difficult to differentiate and a diagnostic laparoscopy may be required.

  5. Ectopic Pregnancy: PID during pregnancy is very rare. In the case of a patient presenting with symptoms of an ectopic pregnancy (abdominal pain, spotting, and positive pregnancy test), this patient should be evaluated for ectopic pregnancy before the diagnosis of PID is considered.

  6. Cystitis/Pyelonephritis: Patients with significant cystitis may have abdominal and pelvic pain. They may have pain when palpating the bladder during bimanual exam or low back and costovertebral angle (CVA) pain with pyelonephritis. A urinalysis may be collected to determine if the etiology of infection is more likely a urinary pathogen rather than PID. These patients are also less likely to have cervical mucopus, leukorrhea, or cervical motion tenderness.

  7. Diverticulitis: patients with suspected diverticulitis or rupture diverticulum should be evaluated with a CT scan of the abdomen and pelvis.

3. Management

The goal of PID treatment is to provide broad spectrum antimicrobial therapy that will cover any of the likely pathogens. Most PID infections are polymicrobial and involve a mix of aerobic and anaerobic microorganisms. All therapeutic regimens used to treat PID should adequately treat gonorrhea, Chlamydia, gram-negative enteric bacilli, streptococci, and anaerobes. Patients with concurrent bacterial vaginosis should receive additional therapy to treat vaginitis.

Patients with mild-moderate PID may be treated as outpatients, whereas women with more severe acute PID may require hospitalization and parenteral therapy. Outpatients should follow up within 48-72 hours to determine if they are symptomatically improving and if not admission should be considered. Criteria for admission include:

  1. nausea and vomitting with inability to tolerate oral therapy

  2. high fever or severe clinical illness

  3. tubo-ovarian abscess

  4. inability to comply with therapy and follow up

  5. cannot exclude surgical condition, i.e. appendicitis

  6. pregnancy

Various emperic antimicrobial regimens have been studied. Due to rising gonococcal fluoroquinolone resistance, this drug class is no longer considered adequate as a component of therapy. Physicians must consider drug availability, cost, and patient tolerance when determining which regimen is best for the individual patient.

CDC recommendations for outpatient antimicrobial therapy:

A. Ceftriaxone 250 mg intramuscularly (IM) once

AND

Doxycycyline 100 mg by mouth (PO) twice daily (BID) for 14 days

AND in cases of concurrent bacterial vaginosis

Metronidazole 500 mg PO BID for 14 days

B. Cefoxitin 2 gm IM once

WITH

Probenecid 1 gm PO once

AND

Doxycycyline 100 mg by mouth (PO) twice daily (BID) for 14 days

AND in cases of concurrent bacterial vaginosis

Metronidazole 500 mg PO BID for 14 days

CDC recommendations for inpatient parenteral antimicrobial therapy

A. Cefotetan 2 gm intravenously (IV) every 12 hours

AND

Doxycycline 100 mg IV every 12 hours (change to oral therapy when patient can tolerate PO)

B. Cefoxitin 2 gm IV every 6 hours

AND

Doxycycline 100 mg IV every 12 hours (change to oral therapy when patient can tolerate PO)

C. Clindamycin 900 mg IV every 8 hours

AND

Gentamicin loading dose 2 mg/kg IV followed by 1.5 mg/kg IV every 8 hours (may substitute daily dosing 3-5 mg/kg/day)

D. Ampicillin/sulbactam 3 gm IV every 6 hours

Doxycycline 100 mg IV every 12 hours (change to oral therapy when patient can tolerate PO)

Parenteral therapy may be discontinued following 24 hours of clinical improvement. Patients should be discharged with two weeks of oral therapy to treat PID.

Discharge medications following parenteral therapy:

1. Doxycycline 100 mg PO BID for 14 days

AND in cases of concurrent bacterial vaginosis

Metronidazole 500 mg PO BID for 14 days

2. Clindamycin 450 mg PO QID for 14 days

4. Complications

Immediate Complications

  • Ruptured tubo-ovarian abscess and peritonitis

  • Failure to respond to outpatient management, requiring hospital admission

  • Misdiagnosis

Long-term Sequelae:

  • Chronic pelvic pain

  • Infertility

  • Ectopic pregnancy

  • Recurrent infection

A high clinical suspicion and readiness to provide emperic treatment in women at risk are the best strategies for lowering a woman's risk for long-term sequelae. Early recognition and treatment of PID are key in decreasing a woman's risk of long-term sequelae.

Consequences of Treatment

Consequences of therapy are rare. Patients may have an adverse reaction to the antimicrobial therapy provided. Patients with large tubo-ovarian abscesses may not respond to parenteral antibiotics and may require surgical drainage of the abscess. Hysterectomy is rarely needed to treat PID.

5. Prognosis and outcome

Prognosis and Outcome

Approximately 25% of patients diagnosed with acute PID develop long-term sequelae. The risk for sequelae is increased if the patient has recurrent episodes of PID.

  1. Tubal factor infertility (TFI) - TFI occurs in approximately 8-19% of women after one episode of PID. This is more likely in women with severe acute PID and delayed therapy.

  2. Ectopic pregnancy - this is a potential life-threatening complication of upper genital tract infection. Approximately 2-6% of women with a history PID experience an ectopic pregnancy.

  3. Chronic pelvic pain (CPP) - CPP affects approx 12-24% of women with a history of PID. CPP as a consequence of PID has been studied less extensively than TFI and ectopic pregnancy.

Long-term Impact

Patients with a history of PID are at risk for recurrent upper genital tract infections. These women should be educated about risks associated with PID, such as lack of barrier contraception use and douching, in order to decrease their risk of recurrence. They should also be made aware of the symptoms associated with PID and advised to seek medical attention if they develop such symptoms. Despite treatment, patients may develop long-term sequelae such as chronic pelvic pain, infertility, and ectopic pregnancy.

6. What is the evidence for specific management and treatment recommendations

Workowski, KA, Berman, S. "Sexually transmitted diseases treatment guidelines, 2010". MMWR Recomm Rep. vol. 59. Dec17. pp. 1-110.

(The CDC STD Guidelines are an excellent resource for clinicians in regards to the treatment of pelvic inflammatory disease. These guidelines are composed by a panel of experts. The recommendations made are based on the existing evidence and the publications perceived to be most influential in PID research and management.)

Ness, RB, Soper, DE, Holley, RL. "Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial". Am J Obstet Gynecol. vol. 186. 2002. pp. 929-37.

(The PEACH trial is considered a landmark article in PID management. This randomized controlled trial demonstrated that reproductive outcomes in women with mild-moderate PID had similar outcomes following inpatient and outpatient therapy.)

Soper, DE. "Pelvic inflammatory disease". Obstet Gynecol. vol. 116. 2010. pp. 419-28.

(Dr. Soper is one of the contributing authors to the PEACH trial. This review paper in Obstetrics and Gynecology is an excellent up to date source for PID pathophysiology, diagnosis, treatment, and long-term outcomes.)

Eschenbach, DA, Wolner-Hanssen, P, Hawes, SE, Pavletic, A, Paavonen, J, Holmes, KK. "Acute pelvic inflamatory disease: associations of clinical and laboratory findings with laparoscopic findings". Obstet Gynecol. vol. 89. 1997. pp. 184-92.

(This observational trial enrolled 155 women with suspected PID. Clinical and laboratory data were collected before women underwent diagnostic laparoscopy. The findings of this trial suggest that clnical and laboratory criteria for the diagnosis for PID have a low sensitivity for obvious tubal disease at the time of laparoscopy.)

Wiesenfeld, HC, Hillier, SL, Krohn, MA. "Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease". Obstet Gynecol. vol. 100. 2002. pp. 456-63.

(This cross-sectional study determined the rate of subclinical PID of women attending an STI clinic for complaints of vaginitis/ cervicitis. Women with clinical PID were excluded. Approximately one quarter of women with Chlamydia or gonorrhea had histiologic evidence of asymptomatic endometritis.)

Peipert, JF, Ness, RB, Blume, J. "Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease". Am J Obstet Gynecol. vol. 184. 2001. pp. 856-63.

(This observational study demonstrated that the minimal clinical criteria for the diagnosis of PID has a low sensitivity based on confirmatory endometrial biopsy. Sensitivity of clinical diagnosis PID was improved when the patient had adnexal tenderness on exam.)

Westrom, L, Joesoef, R, Reynolds, G, Hagdu, A, Thompson, SE. "Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results". Sex Transm Dis. vol. 19. 1992 . pp. 185-92.

(This observational study conducted in Sweden followed women who underwent diagnostic laparoscopy for suspected PID to monitor reproductive outcomes. 16% of women with a history of confirmed PID were unable conceive. 10% of these women had TFI. 9% of women with PID in this trial experienced an ectopic pregnancy.)

Savaris, RF, Teixeira, LM, Torres, TG, Edelweiss, MI, Moncada, J, Schachter, J. "Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial". Obstet Gynecol. vol. 110. 2007. pp. 53-60.

(This Brazilian study randomized women with mild-moderate PID to either ceftriaxone and doxycycline or ceftriaxone and azithromycin. These treatments were equivalent in regards to patients' resolution of pelvic pain post-therapy.)

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