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VOL. 116, NO. 2, PART 1, AUGUST 2010 OBSTETRICS & GYNECOLOGY 419
polymicrobial.13,14 Anaerobic and facultative aerobic
bacteria with and without N gonorrhoeae and C trachomatis
have been isolated from the upper genital tract in up to
70% of women with PID. Rarely, respiratory pathogens,
eg, Haemophilus influenzae and Streptococcus pneumoniae,
can be isolated from the fallopian tubes of women with
salpingitis.
There has been a recent resurgence of interest in
the sexually transmitted pathogen, Mycoplasma geni-
talium, as a possible cause of PID. Haggerty and col-
leagues15 reported the detection of M genitalium from the
endocervix or endometrium or both in 14% of women
with non-gonococcal, non-chlamydial PID, and the mi-
Fig. 1. Microorganisms from the lower genital tract ascend croorganism has been isolated from the fallopian tube of
into the endometrium, fallopian tubes, and peritoneum to a patient with visually confirmed salpingitis.16 M genitali-
cause endometritis-salpingitis-peritonitis (pelvic inflammatory
disease). The arrows indicate the “flow” of microorganisms um–associated PID appears to present with mild clinical
from the lower genital tract to the upper genital tract. This is symptoms similar to chlamydial PID.17
noted as an ascending infection in the text. Reprinted from: There is little to no long-term morbidity associated
Soper DE. Upper genital infections. In: Copeland LJ, ed. with cervcitis or endometritis without the concurrent
Texbook of gynecology. Philadelphia (PA): WB Saunders, association of salpingitis.18 Once infection-induced in-
1993:521. Copyright © 1993 Elsevier.
flammation reaches the fallopian tube, epithelial degen-
Soper. Pelvic Inflammatory Disease. Obstet Gynecol 2010.
eration and deciliation of ciliated cells occurs along the
fallopian tube mucosa in association with a submucosal
mon, suggesting effective containment or efficient elim- inflammatory cell infiltrate.19 There is an associated
ination of pathogens.5 edema of the fallopian tube that augments the intralu-
The sexually transmitted microorganisms Neisseria minal agglutination that occurs with endosalpingitis and
gonorrhoeae and Chlamydia trachomatis have been isolated leads to clubbing of the involved fallopian tube(s). This
from the cervix, endometrium, and fallopian tube of leads to a dysfunctional, partially or totally obstructed
women with histologically confirmed endometritis and fallopian tube causing infertility or ectopic pregnancy.
visually confirmed salpingitis. They are universally ac- Peritonitis is characterized by a fibrinoid exudate on the
cepted as etiologic agents of PID.6,7 Bacterial vaginosis is serosal surfaces of the uterus, tubes, and ovaries leading
present in up to two thirds of women with PID.8 to an agglutination of the tubes, ovaries, bowel, and
Bacterial vaginosis is a complex alteration of the vaginal omentum to the pelvic structures and to each other
microflora in which the normal lactobacilli dominant (Fig. 2).20 This agglutination matures to both filmy
vaginal flora are replaced with an anaerobic dominant and thick pelvic adhesive disease, which is a well-
microflora in association with increasing concentrations known cause of pelvic pain.
of Gardnerella vaginalis and genital mycoplasmas. The
microbial milieu of bacterial vaginosis is associated with DIAGNOSIS
the elaboration of a variety of mucolytic proteinases that The clinician needs to consider PID in the differential
appear to degrade the mucous plug and the natural diagnosis of women presenting to their offices or
occurring antimicrobials, eg, secretory leukocyte pro- emergency departments. The diagnosis is dependent
tease inhibitor, that reside on the genital tract mu- on the elements of patient evaluation: history, physi-
cosa.9,10 This potentiates the development of cervical cal examination, laboratory studies, and imaging.
inflammation and may facilitate ascending infection by If women with the clinical diagnosis of PID were
cervical and vaginal microorganisms, thus resulting in to undergo routine laparoscopy, visual evidence of
endometritis and salpingitis.11 “Bacterial vaginosis mi- acute tubal inflammation (erythema, edema, and pu-
croorganisms,” particularly anaerobic gram-negative rulent exudate) would be confirmed approximately
rods, are associated with upper genital tract inflamma- 65% of the time.21 Therefore, the clinical diagnosis of
tion.12 Bacterial vaginosis, therefore, not only facilitates PID may represent women with visually confirmed
ascending spread of vaginal microorganisms by interfer- acute salpingitis. However, the clinical diagnosis of
ing with the host’s defenses but also provides an inocu- PID may also represent women with cervicitis and
lum of potentially pathogenic microorganisms. The mi- endometritis without salpingitis or with cervicitis
crobial etiology of PID can be referred to as alone.22,23 Chlamydia trachomatis, N. gonorrhoeae, bacte-
VOL. 116, NO. 2, PART 1, AUGUST 2010 Soper Pelvic Inflammatory Disease 421
sage of a cotton swab through the cervical os).30 In of a pelvic mass, which might suggest the presence of
addition, evaluation for bacterial vaginosis (vaginal a tuboovarian abscess.
pH, clue cells, and whiff test) and trichomonas vagi- Laboratory testing adds little to the diagnosis of
nitis is in order. Finally, nucleic acid amplification PID. The peripheral white blood cell count is com-
testing for N. gonorrhoeae and C. trachomatis should be monly normal in women with PID. While the eryth-
performed. If the cervix is normal and no white blood rocyte sedimentation rate (ESR) or C-reactive protein
cells are noted during microscopy of the vaginal is commonly elevated in women with confirmed
secretions, an alternative diagnosis should be investi- salpingitis, the results of these tests are not rapidly
gated since this reliably excludes (negative predictive available in most laboratories. A more thorough
value 94.5%) upper genital tract infection.31 evaluation, including a complete blood count and
Clinicians should maintain a low threshold for erythrocyte sedimentation rate, is recommended for
the diagnosis of PID. The diagnosis should be consid- the woman with clinically severe PID.26,32 Women
ered in sexually active women with or without lower with a clinical diagnosis of PID should be screened for
abdominal pain and symptoms noted in Box 1. A human immunodeficiency virus (HIV).
physical examination should be performed assessing Imaging is most helpful when ruling out compet-
the abdomen for tenderness. A pH of the vaginal ing differential diagnoses such as the use of pelvic
secretions should be performed along with a whiff test ultrasonography to rule out symptomatic ovarian
to assess for the presence of bacterial vaginosis. cysts and computed tomography to rule out appendi-
Microscopy of the vaginal secretions (wet mount) citis.33,34 Pelvic ultrasonography has limited sensitivity
should be examined for the presence of leukocytes as for the diagnosis of PID, but the specific finding of
well as clue cells and trichomonads (Fig. 3). The thickened fluid-filled tubes by ultrasonography sup-
cervical canal should be examined for the presence of ports the diagnosis of upper genital tract inflamma-
yellow or green mucopus and friability and testing for tion. Pelvic ultrasonography should be ordered in
C. trachomatis and N. gonorrhoeae should be performed. patients requiring hospitalization or those with a
A bimanual pelvic examination should be performed pelvic mass noted on bimanual pelvic examination to
to assess for pelvic organ tenderness and for evidence further characterize what is likely to be a tuboovarian
abscess.35
TREATMENT
Women with evidence of lower genital tract infection/
inflammation and no pelvic organ tenderness can be
treated for an uncomplicated lower genital tract infec-
tion or cervicitis (Box 2).28,36 Although a significant
proportion of these women will have histologic evi-
VOL. 116, NO. 2, PART 1, AUGUST 2010 Soper Pelvic Inflammatory Disease 423
lent cure rates. Azithromycin, for the reasons enumer-
ated above, is an acceptable and possibly superior Box 4. Criteria for Hospitalization in Women
alternative to doxycycline. Caution should be exer- With Pelvic Inflammatory Disease
cised when using this agent as monotherapy for PID
because of its suboptimal coverage of N. gonorrhoeae Surgical emergencies (eg appendicitis) cannot be ex-
(Box 3). Topical therapy for concurrent bacterial cluded
vaginosis should avoid the poor tolerability of oral Patient is pregnant
metronidazole regimens.55 Patient does not respond clinically to oral antibiotic
Women with severe PID or the criteria noted in therapy
Box 4 or both should be considered for hospitaliza- Patient is unable to follow or tolerate an outpatient oral
regimen
tion and inpatient parenteral therapy. Patients with
severe PID are more likely to have gonococcal or Patient has severe illness, nausea and vomiting or high
fever
non-chlamydial polymicrobial PID. Given that up to
Patient has a tuboovarian abscess
one third of women hospitalized with severe PID will
have evidence of tuboovarian abscess, imaging with
Data from reference 28.
pelvic ultrasonography or computed tomography is
recommended.56 Although 75% of women with tubo-
ovarian abscess will respond to antibiotic therapy hypoxic abscess environment. In addition, Escherichia
alone, some will fail to respond and require surgical coli is a common isolate from those patients with
drainage. The need for surgical intervention is related ruptured tuboovarian abscess, and is a well-recog-
to the size of the tuboovarian abscess with 60% of nized cause of gram-negative sepsis, making coverage
those women with abscesses 10 cm or greater in of this microorganism critical. Although regimens
diameter, 30% of those measuring 7 to 9 cm, and only containing an aminoglycoside have been used effec-
15% of those 4 to 6 cm in diameter needing surgery.57 tively in women with pelvic abscesses, this class of
Those patients failing to respond to antibiotic treat- antibiotic have their activity significantly reduced at
ment within 48 to 72 hours as characterized by low pH, at low oxygen tension, and in the presence of
persistent fever, an increasing size of tuboovarian drug-binding purulent debris.58 McNeeley et al59
abscess, and a persistent or increasing leukocytosis, showed that the combination of clindamycin and
should be considered for surgical drainage. Drainage gentamicin was associated with a significantly lower
of tuboovarian abscess can be effected by laparotomy, response rate (47%) than the combination of clinda-
laparoscopy, or image guided percutaneous routes. mycin/ampicillin/gentamicin (87.5%) when used to
Proper antimicrobial therapy of pelvic abscesses treat patients with tuboovarian abscess. For these
includes antibiotic regimens with activity against an- reasons, an extended spectrum cephalosporin, eg,
aerobic bacteria in addition to an ability to penetrate ceftriaxone may be a better choice to combine with
abscess cavities while remaining stable in an acidic, either clindamycin or metronidazole in treating
women with severe PID with or without a tuboovar-
ian abscess. In addition, extended spectrum cephalo-
Box 3. Outpatient Antibiotic Regimen for sporins have a much higher serum level to minimum
Treatment of Mild-to-Moderate Pelvic inhibitory concentration ratio than the aminoglyco-
Inflammtory Disease* sides. Clindamycin is actively transported into poly-
morphonuclear leukocytes and macrophages and is
Cefoxitin 2 g intramuscularly in a single dose and present in relatively high concentrations, compared
probenicid, 1 g orally administered concurrently in a with peak serum levels, in experimental abscesses.60
single dose Antimicrobial regimens recommended for the treat-
PLUS ment of severe PID and tuboovarian abscess are listed
Doxycycline 100 mg orally twice daily for 14 days in Box 5. Patients should be discharged on a broad-
OR spectrum oral antimicrobial regimen to complete a
Azithromycin 500 mg orally followed by 250 mg orally 14-day course. Recommended oral regimens for dis-
daily for a total of 7 days charge include amoxicillin/clavulanate (875 mg twice
daily) or the combination of trimethoprim/sulfame-
* Topical metronidazole or clindamycin may be used to treat thoxazole (160/800 mg twice daily) and metronida-
concurrent bacterial vaginosis.55
Data from references 51 and 54.
zole (500 mg twice daily) due to excellent polymicro-
bial coverage.
VOL. 116, NO. 2, PART 1, AUGUST 2010 Soper Pelvic Inflammatory Disease 425
likewise follows that treatment of incident infections pelvic inflammatory disease. N Engl J Med 1975;293:
166 –71.
associated with endometritis (N. gonorrhoeae, bacterial
vaginosis, trichomonas vaginitis) would also contrib- 14. Sweet RL. Treatment strategies for pelvic inflammatory dis-
ease. Expert Opin Pharacother 2009;10:823–37.
ute to prevention. The U.S. Preventative Services
15. Haggerty CL, Totten PA, Astete SG, Ness RB. Mycoplasma
Task Force recommends screening for Chlamydia in genitalium among women with nongonococcal, nonchlamydial
sexually active women 25 years of age and younger as pelvic inflammatory disease. Infect Dis Obstet Gynecol 2006;
well as high-risk (multiple sex partners or a history of 2006:30184.
prior sexually transmitted disease or both) women 16. Cohen CR, Mugo NR, Astete SG, Odondo R, Manhart LE,
over 25. Finally, sex partners of women with PID Kiehlbach JA, et al. Detection of Mycoplasma genitalium in
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tected in the patient with PID. These male sex CL. Clinical presentation of Mycoplasma genitalium infection
partners are commonly asymptomatic but still have a versus Neisseria gonorrhoeoe infection among women with pelvic
inflammatory disease. Clin Infect Dis 2009;48:41–7.
strong likelihood of being infected.
18. Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE.
Pelvic inflammatory disease and fertility. A cohort study of
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