Pelvic Inflammatory Disease

Background

Pelvic inflammatory disease (PID) is the syndrome resulting from the ascent of microorganisms from the vagina and cervix to the uterine endometrium, fallopian tubes, ovaries, or contiguous abdominal structures. Many episodes of PID go unrecognized, because of lack of symptoms or mild, nonspecific symptoms (e.g., dyspareunia, abnormal bleeding, and vaginal discharge). Infecting organisms may include Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT), which are sexually transmitted, as well as anaerobic bacteria (Gardnerella vaginalis or Haemophilus influenzae), gram-negative rods (Escherichia coli), Streptococcus agalactiae, gastrointestinal flora, and mycoplasmas (Mycoplasma hominis). It is thought that PID generally is caused by sexually transmitted diseases (STDs) and that additional organisms become involved after infection spreads and protective immunological barriers are disrupted.

Between 20% and 40% of women with cervical chlamydial infection and 10-20% of women with gonococcal infection eventually develop PID, but accurate estimates of the incidence of PID and infertility resulting from GC and CT are difficult to obtain. Hospitalizations for PID declined steadily throughout the 1980s and 1990s but remained relatively constant between 2000 and 2006, at approximately 80,000 annually.

PID is co-epidemic with HIV among some urban populations of reproductive age. Data on PID outcomes among HIV-infected women are limited. Many studies have documented no difference in length or severity of lower abdominal pain, vaginal discharge, fever, abnormal vaginal bleeding, or low back pain between HIV-infected and HIV-uninfected women with PID. However, there is a higher rate of tubo-ovarian abscesses and severe salpingitis and pyosalpinx among HIV-infected women.

Clinical presentation may include salpingitis, endometritis, tubal and ovarian abscess, and pelvic peritonitis, although PID may present with subtle or mild symptoms even in HIV-infected women. Long-term complications of PID may include infertility, ectopic pregnancy, pelvic adhesions, and chronic pain. After a single episode of PID, a woman's risk of ectopic pregnancy increases sevenfold. Approximately 13% of women are infertile after a single episode of PID, 25-35% after two episodes, and 50-75% after three or more episodes.

Diagnosis of PID usually is based on clinical findings, and providers should maintain a low threshold for diagnosing and promptly treating this disease, as it can wreak havoc on a woman's reproductive health. All women who are diagnosed with PID should be tested for GC and CT.

S: Subjective

The patient may complain of mild-to-moderate lower abdominal pain and tenderness, pain with intercourse, vaginal discharge, fever, chills, heavy menstrual bleeding, or other abnormal vaginal bleeding.

Inquire about the following during the history:

  • Symptoms listed above, and duration
  • Sexual history including new sex partner(s) and episodes of unprotected sex
  • Last menstrual period
  • Previous diagnosis of gonorrhea or chlamydia
  • Previous abdominal or gynecologic surgery
  • History of recent intrauterine device (IUD) placement (the risk of PID associated with IUD use is confined primarily to the first 3 weeks after insertion)

O: Objective

Check vital signs with special attention to temperature (may be elevated or normal).

Perform a focused physical examination. Check abdomen (bowel sounds, distention, rebound, guarding, masses, suprapubic and costovertebral angle [CVA] tenderness); perform complete pelvic examination looking for abnormal bleeding or discharge; uterine, adnexal, or cervical motion tenderness; pelvic masses or adnexal enlargement.

A: Assessment

A partial differential diagnosis includes the following:

  • Pregnancy, uterine or ectopic
  • Ruptured or hemorrhagic ovarian cyst
  • Dysmenorrhea
  • Appendicitis
  • Pyelonephritis
  • Diverticulitis
  • Irritable bowel syndrome
  • Cystitis
  • Uterine fibroids/leiomyomas
  • Ovarian torsion
  • Mittelschmerz
  • Kidney stones
  • Pyelonephritis

P: Plan

Diagnostic Evaluation

A diagnosis of PID usually is based on clinical findings; however, the following can support a diagnosis and help rule out other causes of abdominal pain:

  • Pregnancy test
  • Nucleic acid amplification tests (NAAT) or culture for GC and CT
  • Microscopic examination of saline preparation of vaginal secretions

Often, diagnosis must be made and treatment initiated on the basis of clinical criteria. Current guidelines identify "minimal criteria" found on pelvic examination in patients with PID:

  • Cervical motion tenderness, or
  • Uterine tenderness, or
  • Adnexal tenderness

The following signs support a diagnosis of PID:

  • Oral temperature >101°F (>38.3°C)
  • Abnormal cervical or vaginal mucopurulent discharge
  • Presence of abundant numbers of white blood cells on saline microscopy of vaginal secretions (this also can detect concomitant infections such as bacterial vaginosis and trichomoniasis)
  • Elevated erythrocyte sedimentation rate (ESR)
  • Elevated C-reactive protein (CRP)
  • Laboratory documentation of cervical infection with GC or CT (the absence of infection from the lower genital tract, where samples are usually obtained, does not exclude PID and should not influence the decision to treat)

Definitive diagnosis may be made on the basis of:

  • Endometrial biopsy with histopathologic evidence of endometritis
  • Transvaginal sonogram or other imaging showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex
  • Laparoscopic abnormalities consistent with PID

Treatment

Because clinical diagnostic criteria for PID are not always conclusive, presumptive diagnosis and early empiric treatment is common. The positive predictive value of a clinical diagnosis is 65-90%.

Empiric therapy for PID should be started in women who have one or more of the minimal criteria, plus pelvic or lower abdominal pain and risk factors for PID (sexually active young women, women at risk of STDs), unless another cause for the symptoms is identified.

Treatment considerations

Antimicrobial regimens must be broadly effective against likely pathogens (see below). HIV-infected women appear to respond as well to standard antibiotic regimens as do HIV-uninfected women. It is not known whether HIV-infected women with advanced immunosuppression should be treated more aggressively; decisions about whether to use oral or parenteral therapy must be individualized.

In the United States and elsewhere GC commonly is resistant to fluoroquinolone; thus, this class of antibiotics is no longer recommended for treatment of PID.

No evidence suggests that IUDs should be removed in women diagnosed with PID. However, caution should be used if the IUD remains in place, and close clinical follow-up is recommended.

The goals of treatment include the following:

  • Alleviate the pain and systemic malaise associated with infection
  • Achieve microbiological cure
  • Prevent development of permanent tubal damage with associated problems, such as chronic pelvic pain, ectopic pregnancy, and infertility
  • Prevent the transmission of infection to others

Indications for hospitalization of patients with PID include the following:

  • Unsure diagnosis; surgical emergency cannot be excluded
  • Pregnancy
  • Patient does not respond clinically (within 72 hours) to oral antimicrobial therapy
  • Tubo-ovarian abscess
  • Severe illness with nausea and vomiting or high fever
  • Inability to follow or tolerate outpatient regimen

Pregnancy

If the patient is pregnant, aggressive treatment is essential to prevent preterm delivery, fetal loss, and maternal morbidity. Some medications should be avoided to reduce the risk of fetal toxicity; these include doxycycline and gentamicin. Hospitalization for parenteral antibiotic therapy is recommended.

Antibiotic Regimens

Recommended Oral/Outpatient Regimens

  • Ceftriaxone 250 mg IM in a single dose + doxycycline 100 mg PO BID for 14 days, with or without metronidazole 500 mg PO BID for 14 days
  • Cefoxitin 2 g IM in a single dose and probenecid 1 g PO concurrently in a single dose + doxycycline 100 mg PO BID for 14 days, with or without metronidazole 500 mg PO BID for 14 days
  • Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) + doxycycline 100 mg PO BID for 14 days, with or without metronidazole 500 mg PO BID for 14 days

Alternative Oral Regimens

If parenteral cephalosporin therapy is not feasible, consult with an expert. Limited evidence supports the use of amoxicillin/clavulanic acid with doxycycline, and azithromycin with or without metronidazole or ceftriaxone. Because of the prevalence of fluoroquinolone-resistant GC, use of fluoroquinolones is no longer recommended but may be considered, with or without metronidazole, if the community prevalence is low, the patient's risk of gonorrhea is low, and follow-up can be assured if the GC test result is positive. For more information, see the CDC Sexually Transmitted Diseases Treatment Guidelines (see "References," below).

Recommended Parenteral Regimens

  • Cefotetan 2 g IV Q12H + doxycycline 100 mg PO BID
  • Cefoxitin 2 g IV Q6H + doxycycline 100 mg PO BID
  • Clindamycin 900 mg IV Q8H + gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) Q8H; single daily dosing (3-5 mg/kg) may be substituted

Alternative Parenteral Regimen

  • Ampicillin/sulbactam 3 g IV Q6H + doxycycline 100 mg PO BID

Women who are started on oral antibiotics but do not respond within 72 hours should be reevaluated to confirm the diagnosis of PID and should be administered parenteral therapy on either an outpatient or inpatient basis. Patients who are treated with parenteral antibiotics usually can be transitioned to oral antibiotics within 24 hours of clinical improvement.

Follow-Up

  • Patients should show significant clinical improvement within 3 days of initiation of therapy (e.g., improvement in fever, abdominal tenderness, and uterine, adnexal, and cervical motion tenderness). If the patient has not improved, consider hospitalization, additional diagnostic testing, or surgical intervention. Patients who are hospitalized for treatment initially may be switched to an oral regimen and be discharged on oral therapy after they have improved clinically.
  • Evaluate sex partners and offer them treatment if they had sexual contact with the patient during the 60 days preceding the patient's onset of symptoms. Treat empirically for both chlamydia and gonorrhea.
  • If the GC or CT test results are positive, rescreening for GC and CT 3 months after therapy is recommended. Provide education about sexual risk reduction. Instruct patients to use condoms with every sexual contact to prevent reinfection with GC and CT, to prevent other STDs, and to prevent passing HIV to sex partners.
  • Studies of patients treated for CT infection show reinfection rates as high as 13% within 4 months of treatment, highlighting the need for follow-up and partner treatment.

Patient Education

  • Instruct patients to take all of their medications. Advise patients to take medications with food if they feel nauseated, and to contact the clinic promptly if they experience vomiting or are unable to take their medications.
  • Sex partners from the previous 60 days need to be tested for CT, GC, and syphilis (as well as HIV, if uninfected) and treated empirically, as soon as possible, with a regimen effective against GC and CT, even if they have no symptoms. Advise patients to inform their partners that they need to be tested and treated. Otherwise, they may be reinfected.
  • Advise patients to avoid sexual contact until the infection has been cured.
  • Provide education about sexual risk reduction. Instruct patients to use condoms with every sexual contact to prevent becoming reinfected, to prevent other STDs, and to prevent passing HIV to sex partners.
  • Advise patients that PID can recur, and that they should contact the clinic if symptoms such as pain or fever develop.
  • Patients must not drink beer, wine, or any other alcoholic beverage while taking metronidazole, and for at least 24-48 hours after the last dose. Metronidazole may cause a disulfiram-like reaction, resulting in severe nausea and vomiting. Note that patients taking ritonavir capsules may experience symptoms caused by the small amount of alcohol in the capsules; advise patients to contact the clinic if nausea and vomiting occur.

References

  • Abularach S, Anderson J. Gynecologic Problems. In: Anderson JR, ed. A Guide to the Clinical Management of Women with HIV. Rockville, MD: Health Resources and Services Administration, HIV/AIDS Bureau; 2005. Accessed December 1, 2013.
  • Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. MMWR 2010 Dec 17; 59 (No. RR- 12):1-110. Accessed December 1, 2013.
  • Cohn SE, Clark RA. Sexually transmitted diseases, HIV, and AIDS in women. In: The Medical Clinics of North America, vol. 87; 2003:971-995.
  • Handsfield HH, Sparling PF. Gonococcal Infections. In: Goldman L, Ausiello D, eds. Cecil Medicine; 23rd edition. Philadelphia: Saunders Elsevier; 2007.
  • Handsfield HH, Sparling PF. Neisseria Gonorrhoeae. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Vol. 7. New York: Churchill Livingstone; 2010.
  • Trigg BG, Kerndt PR, Aynalem G. Sexually transmitted infections and pelvic inflammatory disease in women. Med Clin North Am. 2008 Sep;92(5):1083-113, x.

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Abbreviations for Dosing Terminology

BID
twice daily
BIW
twice weekly
IM
intramuscular (injection), intramuscularly
IV
intravenous (injection), intravenously
PO
oral, orally
Q2H, Q4H, etc.
every 2 hours, every 4 hours, etc.
QAM
every morning
QD
once daily
QH
every hour
QHS
every night at bedtime
QID
four times daily
QOD
every other day
QPM
every evening
TID
three times daily
TIW
three times weekly