INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Pelvic inflammatory disease (PID) is a spectrum of infections of the female genital tract that includes endometritis, salpingitis, tuboovarian abscess, and peritonitis.

Pathophysiology

PID is caused by organisms ascending to the upper female genital tract from the vagina and cervix. It most commonly is associated with Chlamydia trachomatis and Neisseria gonorrhoeae, but other organisms and, in many cases, multiple organisms, have been isolated.

Anaerobic bacteria, including those in the genera Peptococcus, Peptostreptococcus, and Bacteroides, appear to play an important role. The genital Mycoplasma and Ureaplasma organisms and the gut coliforms also have been isolated from the upper genital tract of women with PID.

Frequency

United States

PID is the single most frequent serious infection encountered by women. The disease afflicts more than 1 million women each year and generates annual health care costs of approximately 4.2 billion dollars. It is responsible for nearly 250,000 hospitalizations per year.

Mortality/Morbidity

Several long-term sequelae have been clearly associated with PID.

• Ectopic pregnancy rates are 12-15% higher in women who have had an episode of PID.
• Tubal occlusion with infertility occurs at a rate of 12-50% in these patients, increasing with each episode of PID.
• Chronic pelvic pain has been associated with PID at an incidence as high as 18% after a single episode of the disease.

Sex

PID is a disease of the female upper genital tract.

Age

Sexually active women younger than 25 years are at greatest risk, although PID can occur at any age.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Most women with PID typically report symptoms of bilateral lower abdominal pain.
• Vaginal discharge
• Low back pain
• Irregular vaginal bleeding
• Depending on the severity of the infection, patients with PID may be minimally symptomatic or may present with toxic symptoms of fever, nausea, vomiting, and severe pain.
• Gonococcal PID is thought to have an abrupt onset with more toxic symptoms than nongonococcal disease.
• Gonorrhea- and chlamydia-associated infections are more likely to cause symptoms toward the end of menses and in the first 10 days following the menstrual period.

Physical

• The lower abdomen is usually tender. This is a very sensitive but nonspecific finding.
• Pelvic examination
• • Mucopurulent cervical discharge
  • Cervical motion tenderness
  • Uterine tenderness
  • Adnexal tenderness (usually bilateral)
• An adnexal mass may be found in more extensive cases, suggesting a tuboovarian abscess, or peritonitis may be present, mimicking an acute surgical abdomen.
• The clinical diagnosis of PID can be difficult and imprecise due to the nonspecific nature of the presenting signs and symptoms.
• • Diagnosis also is complicated because a subset of women with PID appear to exhibit subtle symptoms that often are undiagnosed by a health care provider or are unappreciated by the patient.
  • Due to the serious potential complications of untreated PID and the endemic prevalence of the infection, the Centers for Disease Control and Prevention (CDC) has adopted an approach to maximize diagnosis by using minimal criteria and by urging providers to maintain a low threshold for diagnosis and empiric treatment.
• Minimum criteria for the diagnosis of PID are listed below. Institute empiric treatment of PID when a patient has all of the following minimal clinical criteria in the absence of an established cause other than PID:
• • Lower abdominal tenderness on palpation
  • Adnexal tenderness
  • Cervical motion tenderness
• Additional criteria, especially in women with more severe clinical signs, can be used to increase the specificity of the diagnosis.
• • Oral temperature more than 38.3°C (101°F)
  • Abnormal cervical or vaginal discharge
  • Elevated erythrocyte sedimentation rate (ESR)
  • Elevated C-reactive protein
  • Laboratory documentation of cervical infection with N gonorrhoeae or C trachomatis.

Causes

• N gonorrhoeae and C trachomatis traditionally have been considered the etiologic agents of PID, alone or combined.
• A sexually transmitted disease (STD) organism is not recovered in a third of women with PID.
• Facultative anaerobes consistent with the endogenous vaginal and perineal flora have also been identified as potential etiologic agents in PID. These include the following flora:
• • Gardnerella vaginalis
  • Streptococcus agalactiae
  • Peptostreptococcus species
  • Bacteroides species (other than Bacteroides fragilis)
  • Genital Mycoplasma and Ureaplasma species, coliforms
• Other nongenital pathogens, such as Haemophilus influenzae and Haemophilus parainfluenzae, may be the causes of some PID cases.
• • Actinomyces species have been linked to some PID cases associated with intrauterine device (IUD) usage.
  • In less-developed countries, PID may be due to a granulomatous salpingitis caused by Mycobacterium tuberculosis and Schistosoma species.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• All female patients of childbearing age with lower abdominal pain require a pregnancy test. PID is the most common incorrect diagnosis in missed ectopic pregnancies. While it is rare to have PID in pregnancy, the disease can occur in the first 12 weeks of gestation before the decidua seals off the uterus from ascending bacteria.
• Complete blood count
• • Fewer than 50% of women with acute PID have a white blood cell (WBC) count more than 10,000.
  • An elevated WBC count is not a CDC criterion for diagnosing PID.
• The ESR is included in the CDC's additional criteria for PID. ESR may not be particularly helpful in the ED, however, where other diagnoses that also may elevate ESR are present or under consideration.
• Perform a urinalysis on all patients with lower abdominal pain to exclude cystitis or pyelonephritis.
• Obtain gonorrhea and chlamydia cultures or other detection assays, (eg, enzyme-linked immunosorbent assay [ELISA], fluorescent antibody tests, DNA probes) on all patients during the pelvic examination.

Imaging Studies

• Pelvic ultrasound
• • While pelvic ultrasound is not used in the routine diagnosis of uncomplicated PID, it is a valuable adjunct in the diagnosis of tuboovarian abscess.
  • This imagery also can help diagnose other entities on the differential, including ovarian cyst and ovarian torsion.
• Magnetic resonance imaging is useful in diagnosing pelvic inflammatory disease, but it is not a practical tool due to its limited availability and significant cost.

Other Tests

• Venereal Disease Research Laboratory (VDRL) test
• Rapid plasma reagent test
• HIV test

Procedures

• Some experts believe that PID is rare without a coexisting purulent endocervical infection and recommend a wet-mount examination from the os to look for numerous WBCs.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

• All patients with PID require antibiotics. The CDC recommends several parenteral and oral regimens in the 2002 Guidelines for Treatment of Sexually Transmitted Diseases. These regimens are listed in Medication.
• Treatment should not be postponed due to the evidence that prevention of long-term sequelae is linked with timely administration of appropriate antibiotics.
• Analgesics
• IV fluids, if dehydrated
• Recent studies indicate that oral outpatient treatment is as effective as inpatient parenteral treatment for mild-to-moderate cases of pelvic inflammatory disease. However, the CDC has established the following criteria for hospitalization based on observational data and consensus opinion:
• • Surgical emergencies, such as appendicitis, cannot be excluded.
  • Pregnancy
  • The patient does not respond clinically to oral antimicrobial therapy.
  • The patient is unable to follow or tolerate an outpatient oral regimen.
  • The patient has severe illness, nausea, vomiting, or high fever.
  • The patient has a tuboovarian abscess.
  • The patient is immunodeficient (eg, HIV infection with low CD4 counts, immunosuppressive therapy) or has another disease.

Consultations

• A gynecologist should be consulted if the patient is pregnant or a candidate for admission or if the diagnosis is unclear.
• Surgical consultation is indicated if acute appendicitis or other surgical emergency is being considered.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goal of therapy is to resolve the infection.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Clindamycin (Cleocin) plus gentamicin (Gentacidin, Garamycin)
Description	Parenteral regimen B. Clindamycin is a lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest. Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM. If tuboovarian abscess is present, clindamycin is recommended instead of doxycycline.
Adult Dose	Clindamycin 900 mg IV q8h plus gentamicin Loading dose 2 mg/kg IV/IM, followed by a 1.5 mg/kg maintenance dose IV/IM q8h; single dosing of gentamicin may be substituted; parenteral therapy may be discontinued 24 h after clinical improvement; continue doxycycline 100 mg PO bid or clindamycin 450 mg PO qid for 14 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis; non–dialysis-dependent renal insufficiency
Interactions	Increases duration of neuromuscular blockade, induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adjust dose in severe renal and hepatic dysfunction; associated with severe and possibly fatal colitis; narrow therapeutic index (not intended for long-term therapy); caution in myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission

Drug Name	Ofloxacin (Floxin) plus metronidazole (Flagyl)
Description	Ofloxacin is a pyridine carboxylic acid derivative with broad-spectrum bactericidal effects against N gonorrhoeae and C trachomatis. Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents.
Adult Dose	Inpatient: Ofloxacin 400 mg IV q12h plus metronidazole 500 mg IV q8h Outpatient: Ofloxacin 400 mg PO bid for 14 d plus metronidazole 500 mg PO bid for 14 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); may increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal and hepatic function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; monitor for seizures and development of peripheral neuropathy

Drug Name	Ampicillin and sulbactam (Unasyn) plus doxycycline (Doryx)
Description	Ampicillin and sulbactam is a combination antimicrobial agent that uses a beta-lactamase inhibitor with ampicillin. It covers skin, enteric flora, and anaerobes. It is not ideal for nosocomial pathogens. Doxycycline inhibits protein synthesis and, thus, bacterial growth, by binding with the 30S and, possibly, the 50S ribosomal subunits of susceptible bacteria.
Adult Dose	Ampicillin and sulbactam 3 g IV q6h plus doxycycline 100 mg PO/IV q12h
Pediatric Dose	<8 years: Not recommended > 8 years: Not established
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives; bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Evaluate rash and differentiate from hypersensitivity reaction; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Levofloxacin (Levaquin) plus doxycycline (Doryx)
Description	Levofloxacin antimicrobial activity is based on ability to inhibit bacterial DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Differences in chemical structure between quinolones have resulted in altered levels of activity against different bacteria. Altered chemical structure results in toxicity differences as well. Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding with the 30S and, possibly, the 50S ribosomal subunits of susceptible bacteria.
Adult Dose	Levofloxacin 500 mg PO/IV qd for 14 d plus doxycycline 100 mg PO/IV q12h for 14 d
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations
Pregnancy	D - Unsafe in pregnancy
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Ceftriaxone (Rocephin) or cefoxitin (Mefoxin) plus doxycycline (Doryx)
Description	This regimen is theoretically limited by poor anaerobic coverage. Depending on the clinical situation, consider adding metronidazole. Use of PO cephalosporins is not recommended for PID, only for cervicitis and urethritis.
Adult Dose	Ceftriaxone 250 mg IM once or cefoxitin 2 g IM plus probenecid 1 g PO in single dose once concurrently plus doxycycline 100 mg PO bid for 14 d
Pediatric Dose	<8 years: Not recommended > 8 years: Not established
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity; bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; caution in breastfeeding women and allergy to penicillin

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Clinical improvement should occur within 3 days of initiating therapy.
• Consider further diagnostic tests and/or laparoscopy if symptoms do not improve or worsen.
• Surgical intervention may be indicated in patients with an enlarging pelvic mass despite medical therapy, intraperitoneal bleeding secondary to erosion into a vessel, or abscess rupture.
• Remove IUDs following institution of antibiotics.

Further Outpatient Care

• Continue oral antibiotics for a full 2 weeks.
• Follow-up is suggested in 3 days to monitor clinical improvement.
• Sexual abstinence is advised until cure is achieved.
• Treatment of sexual contacts is essential to prevent reinfection.
• The CDC recommends the treatment of partners who have had sex with the patient during the 60 days preceding onset of symptoms.

Transfer

• Transfer is advised only if a patient is stable and only if the hospital is incapable of managing acutely ill patients with gynecological emergencies.

Deterrence/Prevention

• All patients should routinely receive sexual counseling, including advice to practice safe sex with the use of condoms. Other areas of discussion include limiting the number of sexual partners and avoiding contact with high-risk partners. Adolescents should be advised to delay the onset of sexual activity until the age of 16 or older, as they are at an increased risk for PID.
• Barrier contraceptives (eg, diaphragms with spermicidal agents) and oral contraceptives are thought to reduce the risk for developing PID.
• IUDs predispose patients to PID, predominantly during the first few months after insertion.
• Frequent vaginal douching was considered to be a risk factor for PID, but recent studies reveal no clear association.

Complications

• Ectopic pregnancy is 6 times more likely in women who have had PID than in those who have not.
• Tubal damage and scarring can result in infertility. One study demonstrated infertility in 8% of women after a single PID episode and in 40% of women after 3 or more episodes.
• One investigator found chronic pelvic pain in up to 18% of women after PID had resolved.

Prognosis

• The prognosis is good if diagnosed and treated early.
• A poor prognosis is related to late therapy and continued unsafe lifestyle.

Patient Education

• Emergency physicians should emphasize behavioral and contraceptive methods to prevent the acquisition of STDs.
• HIV testing should be recommended.
• Patients must be encouraged to complete the recommended antibiotic treatment for the full 14 days.
• Sexual partners of patients diagnosed with PID must be treated to prevent reinfection.
• For excellent patient education resources, visit eMedicine's Women's Health Center, Sexually Transmitted Diseases Center, and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Pelvic Inflammatory Disease, Birth Control Overview, Birth Control FAQs, and Female Sexual Problems.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose and treat patients with PID in a timely manner
• Failure to test for pregnancy and potentially to misdiagnose ectopic pregnancy
• Failure to obtain a medication allergy history
• Failure to test for syphilis
• Failure to advise that sexual partners must be treated

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• CDC. 1998 guidelines for treatment of sexually transmitted diseases. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. Jan 23 1998;47(RR-1):1-111. [Medline].
• CDC. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR Recomm Rep. May 10 2002;51(RR-6):1-78. [Medline].
• Hillis SD, Joesoef R, Marchbanks PA. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol. May 1993;168(5):1503-9. [Medline].
• Hollier LM, Workowski K. Treatment of sexually transmitted diseases in women. Obstet Gynecol Clin North Am. Dec 2003;30(4):751-75, vii-viii. [Medline].
• McCormack WM. Pelvic inflammatory disease. N Engl J Med. Jan 13 1994;330(2):115-9. [Medline].
• Ness RB, Hillier SL, Kip KE. Douching, pelvic inflammatory disease, and incident gonococcal and chlamydial genital infection in a cohort of high-risk women. Am J Epidemiol. Jan 15 2005;161(2):186-95. [Medline].
• Ness RB, Hillier SL, Kip KE. Bacterial vaginosis and risk of pelvic inflammatory disease. Obstet Gynecol. Oct 2004;104(4):761-9. [Medline].
• Ness RB, Trautmann G, Richter HE. Effectiveness of treatment strategies of some women with pelvic inflammatory disease: a randomized trial. Obstet Gynecol. Sep 2005;106(3):573-80. [Medline].
• Rice R, Schwartz D, Knapp J, et al. Pelvic inflammatory disease. In: Morse, Moreland, Holmes, eds. Atlas of Sexually Transmitted Diseases and AIDS. 1996;134-47. [Medline].
• Soper DE. Pelvic inflammatory disease. Infect Dis Clin North Am. Dec 1994;8(4):821-40. [Medline].
• Westrom L, Joesoef R, Reynolds G, et al. 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. Jul-Aug 1992;19(4):185-92. [Medline].
• Wiesenfeld HC, Sweet RL, Ness RB. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis. Jul 2005;32(7):400-5. [Medline].

Article Last Updated: Apr 11, 2006