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Chapter 8: Pelvic Inflammatory Disease

Pelvic inflammatory disease (PID) is a term used to describe upper genital tract infections that frequently involve the endometrium (endometritis), fallopian tubes (salpingitis or tubo-ovarian abscess), and pelvic peritoneum (peritonitis). These infections result from ascending spread of lower genital tract infection. Due to the imprecise nature of the clinical diagnosis and likely also to under-reporting, incidence figures are unreliable. Hospitalizations due to PID appeared to decline between the 1980s and 1990s but stabilized between 2000 and 2007. Moreover, consistent with racial disparities in Neisseria gonorrhoeae and Chlamydia trachomatis, rates of PID are two to three times higher among Black women than among White women.

ETIOLOGY

The most common etiologic agents in PID are gonorrhea, chlamydia and several anaerobic bacterial species found in the vagina and associated with bacterial vaginosis (BV), particularly Bacteroides spp., Gardnerella vaginalis, anaerobic Gram-positive cocci, and E. coli. Mycoplasma hominis, Ureaplasma urealyticum and Mycoplasma genitalium may also be pathogens in PID. These organisms initially cause lower genital tract infections and then spread into the upper genital tract via the endometrium. Many cases are polymicrobial in etiology, with two or more of these organisms involved. The relative frequency of the various agents depends somewhat on the population tested, the site cultured (i.e., cervix, endometrium, or Fallopian tubes), and the sensitivity of the diagnostic tests performed.

CLINICAL MANIFESTATIONS AND DIAGNOSIS

All young, sexually active women presenting with lower abdominal pain should be carefully evaluated for the presence of salpingitis and endometritis.  

Although not commonly employed in most practice settings, the most definitive and specific criteria for diagnosis of PID include:

  • Endometrial biopsy demonstrating histopathologic evidence of endometritis;
  • Transvaginal sonography or magnetic resonance imaging techniques showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian complex, or Doppler studies suggesting pelvic infection (e.g., tubal hyperemia); or
  • Laparoscopic abnormalities consistent with PID

History and examination

PID is difficult to accurately diagnose largely because clinical manifestations overlap with a number of other pelvic and intra-abdominal conditions, including appendicitis, cholecystitis, ovarian cyst rupture, and endometritis. However, given the serious sequelae associated with untreated PID, clinicians should maintain a low threshold to begin treatment for PID empirically in a young sexually active woman who presents with abnormal vaginal discharge, lower abdominal pain or dyspareunia. (See algorithm below in Figure 8-1). Patients with PID may also complain of pain with menses, menometorrhagia, fever, nausea or vomiting.

 Figure 8-1 for evaluation and management of PID.

Figure 8-1 reproduced with the permission of the Sylvie Ratelle STD/HIV Prevention Training Center of New England

Presumptive treatment for PID should be initiated in the presence of intentionally broad clinical criteria below:

  • • cervical motion tenderness
  • OR
  • • adnexal tenderness
  • OR
  • • uterine tenderness.

Detection of one or more of the following signs in addition to the criteria above can increase the specificity of the diagnosis of PID (CDC 2010 Treatment Guidelines):

  • oral temperature greater than 101° F (or 38.3 C)
  • presence of abundant numbers of WBCs on saline microscopy of vaginal fluid
  • elevated erythrocyte sedimentation rate
  • elevated C-reactive protein
  • laboratory documentation of either chlamydia or gonorrhea

In general, clinicians should err on the side of over-diagnosing and treating milder cases.

DIFFERENTIAL DIAGNOSIS

PID should be distinguished from a wide variety of other intra-abdominal and pelvic conditions. Women with unilateral adnexal mass lesions and an atypical history on physical examination should be carefully evaluated for ectopic pregnancy, ruptured ovarian cyst, pyelonephritis, appendicitis, or PID. A history or signs of fetal expulsion, in addition to heavy vaginal bleeding and acute onset, suggests a miscarriage or ruptured ectopic pregnancy. Such patients, or patients in whom the diagnosis is unclear, should be referred for further evaluation.

Decision to hospitalize should be based on the following criteria:

  • Surgical emergency (e.g., appendicitis) cannot be excluded
  • Pregnancy
  • Lack of clinical response to oral antimicrobial therapy
  • Inability to follow or tolerate an outpatient oral regimen
  • Severe illness, nausea and vomiting, or high fever
  • Presence of tubo-ovarian abscess

TREATMENT

For a more detailed discussion of these regimens and other treatment considerations, please refer to the CDC STD Treatment Guidelines at http://www.cdc.gov/std/treatment/.

Since it is usually not known which etiologic agents are involved when PID is diagnosed in a given patient, broad spectrum antimicrobial coverage should be provided to cover gonorrhea, chlamydia, and anaerobes. Patients should be advised to rest for 1 to 3 days or until symptoms have resolved or pain is significantly improved and to avoid coitus through the course of antibiotic treatment (usually a minimum of 2 weeks).

Among individuals who meet criteria for hospitalization or who do not improve after 24-48 hours of oral therapy, parenteral therapy should be administered. Treatment regimens described below represent recommendations from the CDC's 2010 STD Treatment Guidelines.

Recommended Parenteral Regimen A

Cefotetan 2 g IV every 12 hours

OR

Cefoxitin 2 g IV every 6 hours

PLUS

Doxycycline 100 mg orally or IV every 12 hours

Recommended Parenteral Regimen B

Clindamycin 900 mg IV every 8 hours

PLUS

Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3–5 mg/kg) can be substituted.

After a clinical response has been achieved (generally after 24-48 hours), parenteral therapy can be discontinued and the patient can complete 14 days of therapy with clindamycin 450 mg PO QID (preferred if tubo-ovarian abscess is present), or doxycycline 100 mg PO BID.

The following regimen has at least one study to support its use (McGregor, Crombleholme et al. 1994):

Alternative Parenteral Regimens

Ampicillin/Sulbactam 3 g IV every 6 hours

PLUS

Doxycycline 100 mg orally or IV every 12 hours

One trial demonstrated high short-term clinical cure rates with azithromycin, either as monotherapy for 1 week (500 mg IV for 1 or 2 doses followed by 250 mg orally for 5–6 days) or combined with a 12-day course of metronidazole (Bevan, Ridgway et al. 2003).

Oral Antibiotic Regimens

Oral therapy may be considered in those with mild cases of PID when the patient is able to adhere to an oral regimen and appropriate follow-up. Patients who do not improve on oral therapy within 48 hours should be re-evaluated and considered for inpatient admission.

Recommended Regimens

Ceftriaxone 250 mg IM in a single dose

PLUS

Doxycycline 100 mg orally twice a day for 14 days

WITH or WITHOUT*

Metronidazole 500 mg orally twice a day for 14 days


OR

Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose

PLUS

Doxycycline 100 mg orally twice a day for 14 days

WITH or WITHOUT*

Metronidazole 500 mg orally twice a day for 14 days


OR

Other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime)

PLUS

Doxycycline 100 mg orally twice a day for 14 days

WITH or WITHOUT*

Metronidazole 500 mg orally twice a day for 14 days

*Clear guidelines for the addition of metronidazole to the above regimens do not exist. However, because the presence of BV denotes an abundance of vaginal anaerobes that may be involved in upper reproductive tract infection, some experts endorse the routine addition of metronidazole when BV is present in the setting of PID.

Alternative Regimens

As a result of the emergence of quinolone-resistant gonorrhea, regimens that include a quinolone agent are no longer recommended for the treatment of PID. If parenteral cephalosporin therapy is not feasible, use of fluoroquinolones (levofloxacin 500 mg orally once daily or ofloxacin 400 mg twice daily for 14 days) with or without metronidazole (500 mg orally twice daily for 14 days) might be considered if the community prevalence and individual risk for gonorrhea are low, though this option may become increasingly unfeasible in the future. If fluoroquinolones are used, it is especially important that diagnostic tests for gonorrhea (ideally culture if available) be performed before instituting therapy and the patient managed as follows if the test is positive:

  • If culture for gonorrhea is positive, treatment should be based on results of antimicrobial susceptibility.
  • If the isolate is determined to be quinolone-resistant N. gonorrhoeae (QRNG) or if antimicrobial susceptibility cannot be assessed (e.g., if only NAAT testing is available), parenteral cephalosporin is recommended. However, if cephalosporin therapy is not feasible, the addition of azithromycin 2 g orally as a single dose to a quinolone-based PID regimen is recommended.

Finally, although not yet a part of common clinical practice, multiple studies have evaluated the efficacy of oral moxifloxacin (400 mg orally daily) and found it to be effective and well tolerated among women with acute uncomplicated PID (Judlin, Liao et al. 2010, Heystek et al 2009, Ross et al 2006).

FOLLOW-UP

Patients should exhibit clinical signs of improvement within 72 hours of either oral or parenteral therapy for PID. If this is not observed, practitioners should re-evaluate the diagnosis of PID or consider infection with antibiotic-resistant gonorrhea.

Women with documented chlamydial or gonococcal infections should be retested 3-6 months after initial diagnosis. All women with PID should undergo testing for HIV infection.

MANAGEMENT OF SEX PARTNERS

Examination and diagnostic tests for gonorrhea and chlamydia should occur for all sex partners within the preceding 60 days, regardless of symptoms. Empirically treat partners with a regimen active against C. trachomatis and N. gonorrhoeae, regardless of the apparent etiology of the PID. Expedited partner therapy may play an effective role in the referral and administration of appropriate therapy for male sexual partners of infected women.

HIV INFECTION

There is no clear evidence to suggest a difference in the clinical manifestations of PID in HIV infected and uninfected women. Ultimately, both HIV infected and uninfected women appear to respond equally and with comparable cure rates to standard PID treatment regimens.

INTRAUTERINE CONTRACEPTIVE DEVICES

Roughly 5.5% of U.S. women who practice contraception use the IUD (Mosher and Jones 2010). Given its relative popularity, providers may encounter women that have signs and symptoms suggestive of PID among IUD users. Although there is some evidence for low risk of infection in the first three weeks following IUD insertion, the risk of PID associated with its use is quite rare thereafter (Grimes 2000). Ultimately, there is insufficient evidence to require removal of IUDs during acute PID or to avoid placing IUDs among women with a history of gonorrhea or chlamydia. Nonetheless, providers are encouraged to closely follow patients diagnosed with PID with retained IUDs.

SEQUELAE

Long term sequelae include chronic pelvic pain, infertility and an increased risk of ectopic pregnancy. As many as one out of four women who acquire PID will experience one or more of these sequelae. Most experts agree that routine screening of young women for chlamydia reduces subsequent risk of PID and related complications.



Reference:
Bevan, C. D., G. L. Ridgway, et al. (2003). Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res 31(1): 45-54. [PubMed]

Grimes, D. A. (2000). Intrauterine device and upper-genital-tract infection. Lancet 356(9234): 1013-1019. [PubMed]

Judlin, P., Q. Liao, et al. (2010). Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study. BJOG 117(12): 1475-1484. [PubMed]

McGregor, J. A., W. R. Crombleholme, et al. (1994). Randomized comparison of ampicillin-sulbactam to cefoxitin and doxycycline or clindamycin and gentamicin in the treatment of pelvic inflammatory disease or endometritis. Obstet Gynecol 83(6): 998-1004. [PubMed]

Mosher, W. D. and J. Jones (2010). Use of contraception in the United States: 1982-2008. Vital Health Stat 23(29): 1-44. [PubMed]

CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR 2012:61(31); 590-594

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