Pelvic inflammatory disease (PID) is an infectious and inflammatory disorder of the upper

female genital tract, including the uterus, fallopian tubes, and adjacent pelvic structures.
Infection and inflammation may spread to the abdomen, including perihepatic structures
(Fitz-HughCurtis syndrome). The classic high-risk patient is a menstruating woman younger
than 25 years who has multiple sex partners, does not use contraception, and lives in an area
with a high prevalence of sexually transmitted disease (STD).
PID is initiated by infection that ascends from the vagina and cervix into the upper genital
tract. Chlamydia trachomatis is the predominant sexually transmitted organism associated
with PID. Other organisms implicated in the pathogenesis of PID include Neisseria
gonorrhoeae, Gardnerella vaginalis, Haemophilus influenzae, and anaerobes such
as Peptococcus and Bacteroides species. Laparoscopic studies have shown that in 30-40% of
cases, PID is polymicrobial. (See Etiology.)
The diagnosis of acute PID is primarily based on historical and clinical findings. Clinical
manifestations of PID vary widely, however: Many patients exhibit few or no symptoms,
whereas others have acute, serious illness. The most common presenting complaint is lower
abdominal pain. Many women report an abnormal vaginal discharge. (See Presentation.)
The differential diagnosis includes appendicitis, cervicitis, urinary tract infection,
endometriosis, and adnexal tumors. Ectopic pregnancy can be mistaken for PID; indeed, PID
is the most common incorrect diagnosis in cases of ectopic pregnancy. Consequently, a
pregnancy test is mandatory in the workup of women of childbearing age who have lower
abdominal pain. (See DDx.)
PID may produce tubo-ovarian abscess (TOA) and may progress to peritonitis and FitzHughCurtis syndrome (perihepatitis; see the image below). Subclinical PID or a delay in
diagnosis or treatment of PID can result in long-term sequelae, such as chronic pelvic pain
and tubal infertility.[1]

"Violin-string" adhesions of chronic Fitz-Hugh-Curtis syndrome.

Laparoscopy is the current criterion standard for the diagnosis of PID. No single laboratory
test is highly specific or sensitive for the disease, but studies that can be used to support the
diagnosis include the erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP)
level, and chlamydial and gonococcal DNA probes and cultures. Imaging studies (eg,
ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI]) may
be helpful in unclear cases. (See ">Workup.)
Most patients with PID are treated in an outpatient setting. In selected cases, however,
physicians should consider hospitalization. (See Treatment.)
Empirical antibiotic treatment is recommended for patients with otherwise unexplained
uterine or adnexal tenderness and cervical motion tenderness, according to guidelines from
the Centers for Disease Control and Prevention (CDC).[2] Antibiotic regimens for PID must be

effective against C trachomatis andN gonorrhoeae, as well as against gram-negative

facultative organisms, anaerobes, and streptococci. (See Treatment and Medication.)

Etiology
The organisms most commonly isolated in cases of acute PID are N gonorrhoeaeand C
trachomatis. C trachomatis is an intracellular bacterial pathogen and the predominant
sexually transmitted organism that causes PID.
In the United States, N gonorrhoeae is no longer the primary organism associated with PID,
but gonorrhea remains the second most frequently reported sexually transmitted disease, after
chlamydial infection. Clinically, gonorrheal infection may be asymptomatic or may manifest
similarly to chlamydial infection; however, it more often produces more acute symptomatic
disease. An estimated 10-20% of untreated chlamydial or gonorrheal infections progress to
PID.
Cultures of specimens collected during laparoscopy have demonstrated that PID is a
polymicrobial infection in as many as 30-40% of cases. Polymicrobial PID may begin as an
isolated infection with N gonorrhoeae or C trachomatis, which causes inflammation of the
upper genital tract that facilitates the involvement of other pathogens (anaerobes, facultative
anaerobes, and other bacteria). These other organisms are increasingly isolated as
inflammation increases and abscesses form.
In addition to N gonorrhoeae and C trachomatis, organisms involved in PID include the
following:

Gardnerella vaginalis
Mycoplasma hominis
Mycoplasma genitalium
Ureaplasma urealyticum
Herpes simplex virus 2 (HSV-2)
Trichomonas vaginalis
Cytomegalovirus (CMV)
Haemophilus influenzae
Streptococcus agalactiae
Enteric gram-negative rods (eg, Escherichia coli)
Enterococcus, described in 2 individuals post IUD insertion [14]
Peptococcus species
Anaerobes
The microbiology of PID reflects the predominant sexually transmitted pathogens within a
specific population, as well as some organisms less commonly seen in that population.
Bacterial vaginosis (BV) may lead to vaginal inflammation, which could facilitate ascending
infection with BV-associated organisms (eg, G vaginalis). In some regions, PID may be from
a granulomatous salpingitis caused byMycobacterium tuberculosis or Schistosoma species.[15]
In a cross-sectional study of 736 women with PID, patients with Trichomonasinfections
demonstrated a 4-fold increase in the histologic evidence of acute endometritis. Coinfection
with HSV-2, N gonorrhoeae, C trachomatis, and BV were associated with histologic
evidence of acute endometritis. HSV-2 was associated with fallopian tube inflammation and

lower tract ulcerations that may contribute to disruption of the endocervical canal mucous
barrier.[16]
HIV infection is associated with an increased incidence of infection with C
trachomatis, Candida, and human papillomavirus (HPV). N gonorrhoeae can facilitate HIV
transmission via modulation of HIV-specific immune responses.[17]Women with HIV infection
also have an increased risk of progression to PID and TOA.[18]
Microbial virulence appears to play a significant role in PID. Bjartling et al studied different
chlamydial strains recovered from patients with PID and found less symptomatic disease in
infection produced by a less virulent variant strain.[19]Features that may increase the
likelihood that a lower tract infection will progress to frank PID include expression of
chlamydial heat shock protein 60 (CHSP60) in C trachomatis[20] and expression of P9Opa(b)
protein in N gonorrhoeae.[21]
Risk factors
Risk factors for PID include multiple sexual partners, a history of prior STIs, and a history of
sexual abuse.[22] Frequent vaginal douching has been considered a risk factor for PID, [23] but
studies reveal no clear association.[24] Gynecologic surgical procedures such as endometrial
biopsy, curettage, and hysteroscopy break the cervical barrier, predisposing women to
ascending infections.[25, 26]
Younger age has been found to be associated with an increased risk of PID. Likely reasons
include increased cervical mucosal permeability, a larger zone of cervical ectopy, a lower
prevalence of protective antichlamydial antibodies, and increased risk-taking behaviors.
Contraception
Different forms of contraception may affect the incidence and severity of PID. Appropriately
used barrier contraception has clearly been shown to decrease the acquisition of most STIs.[27]
Studies of oral contraceptive pills (OCPs) have found differing effects on PID risks. On one
hand, some authors suggest that OCPs increase the risk of endocervical infection, probably
by increasing the zone of cervical ectopy. On the other hand, some evidence indicates that
OCPs can decrease the risk of symptomatic PID, possibly by increasing cervical mucus
viscosity, decreasing menstrual anterograde and retrograde flow, and modifying local immune
responses. Still other studies have suggested that OCPs may not have any effect on PID
incidence.[27]
Use of an intrauterine device (IUD) has been linked to a 2- to 9-fold increased risk of PID,
but current IUDs may pose a substantially lower risk. [28] In a large retrospective cohort study
from 2012, the overall risk of PID in women receiving IUDs was 0.54%.[29]
Kelly et al reported 9.6 cases of PID per 1,000 IUD insertions, with the most significant risk
in the first 20 days.[30] Meirik et al validated the risk of PID within the first month after
insertion and also found that the risk appears to be modified by the patients number of sexual
partners and age and by the community prevalence of STIs. [31] The CDC notes that the risk of
PID is greatly reduced by testing forand, if necessary, treatingSTD before IUD insertion.
[32, 33]
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PID may have a different microbial profile in IUD users. Viberga et al found that in women
with PID, Fusobacterium and Peptostreptococcus species were significantly more common in

IUD users than in non-IUD users. Actinomyces species were found almost exclusively in
patients with IUDs.[34]
Bilateral tubal ligation (BTL) has not been found to provide protection against PID. However,
patients with BTL may have delayed or milder forms of PID.

Physical Examination
Because of the potential serious complications of untreated PID and the endemic prevalence
of the infection, the Centers for Disease Control and Prevention (CDC) has adopted an
approach designed to maximize diagnosis by using minimal criteria. The CDC also urges
clinicians to maintain a low threshold for diagnosis and empiric treatment.
The CDC recommends instituting empiric treatment of PID when a sexually active young
woman who is at risk for STI has pelvic or lower abdominal pain, no identifiable cause for
her illness other than PID, and, on pelvic examination, 1 or more of the following minimal
criteria[2] :

Cervical motion tenderness

Uterine tenderness
Adnexal tenderness
A temperature higher than 38.3 C (101 F) and the presence of an abnormal cervical or
vaginal mucopurulent discharge enhance the specificity of the minimum criteria, as do
selected laboratory tests.
Rebound lower abdominal tenderness and involuntary guarding may be noted and suggest
associated peritonitis. The positive predictive value of these findings will vary, depending on
the prevalence of PID in a given population.
A large multicenter trial found adnexal tenderness to be the most sensitive physical
examination finding (sensitivity, 95%).[48] Mucopurulent cervicitis is common and, if absent,
has substantial negative predictive value. Adnexal fullness or disproportionate unilateral
adnexal tenderness may indicate the development of a tubo-ovarian abscess (TOA).
Molander et al found the following 3 variables to be significant predictors of the diagnosis,
correctly classifying 65% of patients with laparoscopically documented PID[49] :

Adnexal tenderness
Fever
Elevated erythrocyte sedimentation rate (ESR)
Right upper quadrant tenderness, especially if associated with jaundice, may indicate
associated Fitz-HughCurtis syndrome. A prospective cohort study in 117 incarcerated
adolescents documented a 4% incidence of Fitz-HughCurtis syndrome in those with mildto-moderate PID

A number of procedures can be performed to improve the diagnosis of pelvic inflammatory

disease (PID) and its complications. These procedures are not necessary, nor are they
indicated, in the management of every case of PID. However, because of the difficulty of
definitive clinical diagnosis and the number of surgical and gynecologic emergencies that
may have similar presentations, the clinician should be aware of these modalities.
Procedures that may be appropriate for some patients, along with the corresponding findings
specific for PID, are as follows:
Laparoscopic confirmation
Transvaginal ultrasonographic scanning or magnetic resonance imaging (MRI)
showing thickened, fluid-filled tubes with or without free pelvic fluid or tubo-ovarian
abscess (TOA)

Endometrial biopsy showing endometritis

Laparoscopy is the criterion standard for the diagnosis of PID, but the diagnosis of PID in
emergency departments and clinics is often based on clinical criteria, with or without
additional laboratory and imaging evidence.[52] No single test is highly specific and sensitive
for PID, but laboratory tests, imaging studies, and procedures may be used to increase the
specificity of the diagnosis.

Additional criteria that improve diagnostic specificity include the following:

Oral temperature higher than 38.3 C (101 F)

Abnormal cervical or vaginal mucopurulent discharge
Abundant white blood cells (WBCs) on saline microscopy of vaginal secretions
Elevated erythrocyte sedimentation rate (ESR)
Elevated C-reactive protein (CRP) level
Laboratory evidence of cervical infection with N gonorrhoeae or C trachomatis(via
culture or DNA probe)
In addition, obtaining a sample from the urethra in women with suspected PID can increase
the diagnostic yield for gonorrhea and chlamydial infection. This step is recommended only if
the more sensitive nucleic acid amplification test (NAAT) is unavailable

Patients who do not improve in 72 hours should be reevaluated for possible laparoscopic or
surgical intervention and for reconsideration of other possible diagnoses. Laparoscopy should
be used if the diagnosis is in doubt. Laparoscopic pelvic lavage, abscess drainage, and
adhesion lysis may be necessary.
Most TOAs (60-80%) resolve with antibiotic administration. If patients do not respond
appropriately, laparoscopy may be useful for identifying loculations of pus requiring drainage.
An enlarging pelvic mass may indicate bleeding secondary to vessel erosion or a ruptured
abscess. Unresolved abscesses may be drained percutaneously via posterior colpotomy, under
computed tomographic (CT) or ultrasonographic guidance, laparoscopically, or through
laparotomy.
The advantages of laparoscopy include direct visualization of the pelvis and more accurate
bacteriologic diagnosis if cultures are obtained. However, laparoscopy is not always available
in acute PID; moreover, it is costly and requires general anesthesia.
Laparotomy is usually reserved for patients experiencing surgical emergencies (eg, abscesses
that have ruptured or that have not responded to medical management and laparoscopic

drainage) and for patients who are not candidates for laparoscopic management. Treatment is
guided by intraoperative findings and the patients desire for fertility maintenance.
Surgical treatment may involve unilateral salpingo-oophorectomy or hysterectomy and
bilateral salpingo-oophorectomy. Ideally, the operation is performed after the acute infection
and inflammation have resolved. In patients with recurrent PID, dense pelvic adhesions may
render surgery difficult.

Treatment of pelvic inflammatory disease (PID) should include empirical broad-spectrum

antibiotics to cover the full complement of common causes. Antibiotics chosen should be
effective against Chlamydia trachomatis and Neisseria gonorrhoeae, as well as against gramnegative facultative organisms, anaerobes, and streptococci. The Centers for Disease Control
and Prevention (CDC) has outlined antibiotic regimens for outpatient and inpatient treatment
of PID.

Outpatient and inpatient regimens

The Centers for Disease Control and Prevention (CDC) has outlined antibiotic regimens for
outpatient and inpatient treatment of PID.
For outpatient treatment, the CDC lists 2 currently accepted treatment regimens, labeled as A
and B.[2] Regimen A consists of the following:

Ceftriaxone 250 mg intramuscularly (IM) once as a single dose plus

Doxycycline 100 mg orally twice daily for 14 days
Metronidazole 500 mg orally twice daily for 14 days can be added if there is evidence
or suspicion of vaginitis or if the patient underwent gynecologic instrumentation in the
preceding 2-3 weeks
Regimen B consists of the following:

Cefoxitin 2 g IM once as a single dose concurrently with probenecid 1 g orally in a

single dose, or another single-dose parenteral third-generation cephalosporin (eg, ceftizoxime
or cefotaxime) plus
Doxycycline 100 mg orally twice daily for 14 days
Metronidazole 500 mg orally twice daily for 14 days can be added if there is evidence
or suspicion of vaginitis or if the patient underwent gynecologic instrumentation in the
preceding 2-3 weeks

Inpatient treatment
For inpatient treatment of PID, the CDC also lists 2 currently accepted treatment regimens,
again labeled as A and B.[2] Regimen A consists of the following:

Cefoxitin 2 g IV every 6 hours or cefotetan 2 g IV every 12 hours plus

Doxycycline 100 mg orally or IV every 12 hours
This regimen is continued for 24 hours after the patient remains clinically improved, after
which doxycycline 100 mg is given orally twice daily for a total of 14 days. If a TOA is
present, clindamycin or metronidazole is used with doxycycline for more effective anaerobic
coverage.

Regimen B consists of the following:

Clindamycin 900 mg IV every 8 hours plus

Gentamicin IV in a loading dose of 2 mg/kg, followed by a maintenance dosage of 1.5
mg/kg q8h
IV therapy may be discontinued 24 hours after the patient improves clinically, and oral therapy
with 100 mg doxycycline twice daily should be continued for a total of 14 days. If TOA is
present, clindamycin or metronidazole may be used with doxycycline for more effective
anaerobic coverage.
An alternative parenteral regimen is ampicillin-sulbactam 3 g IV every 6 hours in conjunction
with doxycycline 100 mg orally or IV every 12 hours.
(Shepherd S Moore, 2014)