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## Complete Summary

#### GUIDELINE TITLE

Pelvic inflammatory disease. Sexually transmitted diseases treatment
guidelines 2006.

#### BIBLIOGRAPHIC SOURCE(S)

Centers for Disease Control and Prevention, Workowski KA, Berman SM.
Pelvic inflammatory disease. Sexually transmitted diseases treatment
guidelines 2006 \[published errata appear in MMWR Morb Mortal Wkly Rep
2006 Sep 15;55(36):997\]. MMWR Morb Mortal Wkly Rep 2006 Aug
4;55(RR-11):56-61. \[222 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Centers for Disease Control
and Prevention. Pelvic inflammatory disease. Sexually transmitted
diseases treatment guidelines. MMWR Recomm Rep 2002 May
10;51(RR-6):48-52.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse (NGC)**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [July 08, 2008, Fluoroquinolones (ciprofloxacin, norfloxacin,
    ofloxacin, levofloxacin, moxifloxacin,
    gemifloxacin)](http://www.fda.gov/medwatch/safety/2008/safety08.htm#Fluoroquinolone):
    A BOXED WARNING and Medication Guide are to be added to the
    prescribing information to strengthen existing warnings about the
    increased risk of developing tendinitis and tendon rupture in
    patients taking fluoroquinolones for systemic use.

-   [September 11, 2007, Rocephin (ceftriaxone
    sodium)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin):
    Roche informed healthcare professionals about revisions made to the
    prescribing information for Rocephin to clarify the potential risk
    associated with concomitant use of Rocephin with calcium or
    calcium-containing solutions or products.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Pelvic inflammatory disease (PID) including any combination of the
following:

-   Endometritis

-   Salpingitis

-   Tubo-ovarian abscess

-   Pelvic peritonitis

#### GUIDELINE CATEGORY

Diagnosis\
Evaluation\
Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Infectious Diseases\
Internal Medicine\
Obstetrics and Gynecology\
Preventive Medicine

#### INTENDED USERS

Advanced Practice Nurses\
Allied Health Personnel\
Health Care Providers\
Managed Care Organizations\
Nurses\
Physician Assistants\
Physicians\
Public Health Departments

#### GUIDELINE OBJECTIVE(S)

-   To update the Sexually Transmitted Diseases Treatment Guidelines
    2002 (*MMWR 2002;51\[No. RR-6\]*)

-   To assist physicians and other health-care providers in preventing
    and treating sexually transmitted diseases (STDs)

#### TARGET POPULATION

Women with suspected or confirmed pelvic inflammatory disease (PID)

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis**

1.  Laparoscopy

2.  Evaluation of signs and symptoms of pelvic inflammatory disease
    (PID) according to defined criteria:

    -   Uterine, adnexal, or cervical motion tenderness

    -   Oral temperature \>101 degrees F(\>38.3 degrees C)

    -   Abnormal cervical or vaginal mucopurulent discharge

    -   Presence of abundant numbers of white blood cells on saline
        microscopy of vaginal secretions

    -   Elevated erythrocyte sedimentation rate

    -   Elevated C-reactive protein

    -   Laboratory documentation of cervical infection with *Neisseria
        gonorrhoeae* or *Chlamydia trachomatis*

    -   Histopathological evidence of endometritis on endometrial biopsy

    -   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)

    -   Laparoscopic abnormalities consistent with PID

**Treatment/Management**

1.  Hospitalization at the discretion of the health-care provider

2.  Parenteral regimens:

    -   Cefotetan

    -   Cefoxitin plus doxycycline

    -   Clindamycin or metronidazole in addition to doxycycline

    -   Clindamycin plus gentamicin

    -   Ofloxacin or levofloxacin with or without metronidazole

    -   Ampicillin/sulbactam plus doxycycline

3.  Oral treatment regimens

    -   Ofloxacin or levofloxacin with or without metronidazole

    -   Ceftriaxone plus doxycycline with or without metronidazole

    -   Third-generation cephalosporin (e.g. ceftizoxime or cefotaxime)
        plus doxycycline with or without metronidazole

4.  Alternative treatment regimens

    -   Amoxicillin/clavulanic acid plus doxycycline

    -   Azithromycin

5.  Patient follow-up

6.  Evaluation and treatment of sex partners

7.  Preventive screening for chlamydial infection in high-risk women

8.  Special considerations in pregnancy: hospitalization and parenteral
    antibiotics

9.  Special considerations in HIV infection

10. Special considerations for women with intrauterine devices

#### MAJOR OUTCOMES CONSIDERED

-   Microbiologic cure

-   Alleviation of signs and symptoms

-   Prevention of sequelae

-   Prevention of transmission

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Subjective Review

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Beginning in 2004, Centers for Disease Control and Prevention (CDC)
personnel and professionals knowledgeable in the field of sexually
transmitted diseases (STDs) systematically reviewed evidence (including
published abstracts and peer-reviewed journal articles) concerning each
of the major STDs, focusing on information that had become available
since publication of the *Sexually Transmitted Diseases Treatment
Guidelines, 2002*. Background papers were written and tables of evidence
constructed summarizing the type of study (e.g., randomized controlled
trial or case series), study population and setting, treatments or other
interventions, outcome measures assessed, reported findings, and
weaknesses and biases in study design and analysis. A draft document was
developed on the basis of the reviews.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus (Consensus Development Conference)

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

In April 2005, the Centers for Disease Control and Prevention (CDC)
staff members and invited consultants assembled in Atlanta, Georgia, for
a 3-day meeting to present the key questions regarding sexually
transmitted disease (STD) treatment that emerged from the evidence-based
reviews and the information available to answer those questions. When
relevant, the questions focused on four principal outcomes of STD
therapy for each individual disease: 1) microbiologic cure, 2)
alleviation of signs and symptoms, 3) prevention of sequelae, and 4)
prevention of transmission. Cost-effectiveness and other advantages
(e.g., single-dose formulations and directly observed therapy of
specific regimens) also were discussed. The consultants then assessed
whether the questions identified were relevant, ranked them in order of
priority, and attempted to arrive at answers using the available
evidence. In addition, the consultants evaluated the quality of evidence
supporting the answers on the basis of the number, type, and quality of
the studies.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not stated

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**Note from the National Guideline Clearinghouse and the Centers for
Disease Control and Prevention**: When more than one therapeutic regimen
is recommended, the sequence is alphabetized unless the choices for
therapy are prioritized based on efficacy, convenience, or cost. For
sexually transmitted diseases (STDs) with more than one recommended
regimen, almost all regimens have similar efficacy and similar rates of
intolerance or toxicity unless otherwise specified.

Pelvic inflammatory disease (PID) comprises a spectrum of inflammatory
disorders of the upper female genital tract, including any combination
of endometritis, salpingitis, tubo-ovarian abscess, and pelvic
peritonitis. Sexually transmitted organisms, especially *Neisseria
gonorrhoeae* and *Chlamydia trachomatis*, are implicated in many cases;
however, microorganisms that comprise the vaginal flora (e.g.,
anaerobes, *Gardnerella vaginalis, Haemophilus influenzae*, enteric
Gram-negative rods, and *Streptococcus agalactiae*) also have been
associated with PID. In addition, cytomegalovirus (CMV), *Mycoplasma
hominis*, and *Ureaplasma urealyticum* might be the etiologic agents in
some cases of PID. All women who are diagnosed with acute PID should be
tested for *N. gonorrhoeae* and *C. trachomatis* and should be screened
for HIV infection.

**Diagnostic Considerations**

Acute PID is difficult to diagnose because of the wide variation in the
symptoms and signs. Many women with PID have subtle or mild symptoms.
Delay in diagnosis and effective treatment probably contributes to
inflammatory sequelae in the upper reproductive tract. Laparoscopy can
be used to obtain a more accurate diagnosis of salpingitis and a more
complete bacteriologic diagnosis. However, this diagnostic tool
frequently is not readily available, and its use is not easy to justify
when symptoms are mild or vague. Moreover, laparoscopy will not detect
endometritis and might not detect subtle inflammation of the fallopian
tubes. Consequently, a diagnosis of PID usually is based on clinical
findings.

The clinical diagnosis of acute PID is imprecise. Data indicate that a
clinical diagnosis of symptomatic PID has a positive predictive value
(PPV) for salpingitis of 65% to 90% compared with laparoscopy. The PPV
of a clinical diagnosis of acute PID depends on the epidemiologic
characteristics of the population, with higher PPVs among sexually
active young women (particularly adolescents), among patients attending
STD clinics, or in other settings where the rates of gonorrhea or
chlamydia are high. In all settings, however, no single historical,
physical, or laboratory finding is both sensitive and specific for the
diagnosis of acute PID (i.e., can be used both to detect all cases of
PID and to exclude all women without PID). Combinations of diagnostic
findings that improve either sensitivity (i.e., detect more women who
have PID) or specificity (i.e., exclude more women who do not have PID)
do so only at the expense of the other. For example, requiring two or
more findings excludes more women who do not have PID but also reduces
the number of women with PID who are identified.

Many episodes of PID go unrecognized. Although some cases are
asymptomatic, others are not diagnosed because the patient or the
health-care provider fails to recognize the implications of mild or
nonspecific symptoms or signs (e.g., abnormal bleeding, dyspareunia, and
vaginal discharge). Because of the difficulty of diagnosis and the
potential for damage to the reproductive health of women, even by
apparently mild or subclinical PID, health-care providers should
maintain a low threshold for the diagnosis of PID.

The optimal treatment regimen and long-term outcome of early treatment
of women with asymptomatic or subclinical PID are unknown. The following
recommendations for diagnosing PID are intended to help health-care
providers recognize when PID should be suspected and when they need to
obtain additional information to increase diagnostic certainty.
Diagnosis and management of other common causes of lower abdominal pain
(e.g., ectopic pregnancy, acute appendicitis, and functional pain) are
unlikely to be impaired by initiating empiric antimicrobial therapy for
PID.

Empiric treatment of PID should be initiated in sexually active young
women and other women at risk for STDs if they are experiencing pelvic
or lower abdominal pain, if no cause for the illness other than PID can
be identified, and if one or more of the following minimum criteria are
present on pelvic examination:

-   cervical motion tenderness OR uterine tenderness OR adnexal
    tenderness.

The requirement that all three minimum criteria be present before the
initiation of empiric treatment could result in insufficient sensitivity
for the diagnosis of PID. The presence of signs of lower genital tract
inflammation, in addition to one of the three minimum criteria,
increases the specificity of diagnosis. In deciding upon the initiation
of empiric treatment, clinicians should also consider the risk profile
of the patient for STDs.

More elaborate diagnostic evaluation frequently is needed because
incorrect diagnosis and management might cause unnecessary morbidity.
These additional criteria may be used to enhance the specificity of the
minimum criteria. The following additional criteria can be used to
enhance the specificity of the minimum criteria and support a diagnosis
of PID:

-   oral temperature \>101 degrees F (\>38.3 degrees C)

-   abnormal cervical or vaginal mucopurulent discharge

-   presence of abundant numbers of white blood cells (WBCs) on saline
    microscopy of vaginal secretions

-   elevated erythrocyte sedimentation rate

-   elevated C-reactive protein, and

-   laboratory documentation of cervical infection with *N. gonorrhoeae*
    or *C. trachomatis*.

The majority of women with PID have either mucopurulent cervical
discharge or evidence of WBCs on a microscopic evaluation of a saline
preparation of vaginal fluid. If the cervical discharge appears normal
and no WBCs are observed on the wet prep of vaginal fluid, the diagnosis
of PID is unlikely, and alternative causes of pain should be
investigated. A wet prep of vaginal fluid offers the ability to detect
the presence of concomitant infections (e.g., bacterial vaginosis and
trichomoniasis).

The most specific criteria for diagnosing PID include the following:

-   endometrial biopsy with 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); and

-   laparoscopic abnormalities consistent with PID

A diagnostic evaluation that includes some of these more extensive
studies might be warranted in some cases. Endometrial biopsy is
warranted in women undergoing laparoscopy who do not have visual
evidence of salpingitis, as some women with PID have endometritis alone.

**Treatment**

PID treatment regimens must provide empiric, broad spectrum coverage of
likely pathogens. Several antimicrobial regimens have been effective in
achieving clinical and microbiologic cure in randomized clinical trials
with short-term follow-up. However, only a limited number of
investigations have assessed and compared these regimens with regard to
elimination of infection in the endometrium and fallopian tubes or
determined the incidence of long-term complications (e.g., tubal
infertility and ectopic pregnancy) after antimicrobial regimens.

All treatment regimens should be effective against *N. gonorrhoeae* and
*C. trachomatis* because negative endocervical screening for these
organisms does not rule out upper reproductive tract infection. The need
to eradicate anaerobes from women who have PID has not been determined
definitively. Anaerobic bacteria have been isolated from the upper
reproductive tract of women who have PID, and data from in vitro studies
have revealed that some anaerobes (e.g., *Bacteroides fragilis*) can
cause tubal and epithelial destruction. In addition, BV also is present
in many women who have PID. Until treatment regimens that do not
adequately cover these microbes have been demonstrated to prevent
long-term sequelae (e.g., infertility and ectopic pregnancy) as
successfully as the regimens that are effective against these microbes,
the use of regimens with anaerobic activity should be considered.
Treatment should be initiated as soon as the presumptive diagnosis has
been made because prevention of long-term sequelae is dependent on
immediate administration of appropriate antibiotics. When selecting a
treatment regimen, health-care providers should consider availability,
cost, patient acceptance, and antimicrobial susceptibility.

Some specialists have recommended that all patients with PID be
hospitalized so that bed rest and supervised treatment with parenteral
antibiotics can be initiated. However, in women with PID of mild or
moderate clinical severity, outpatient therapy can provide short- and
long-term clinical outcomes similar to inpatient therapy. Limited data
support the use of outpatient therapy in women with more severe clinical
presentations. The decision of whether hospitalization is necessary
should be based on the discretion of the health-care provider.

The following criteria for hospitalization are suggested:

-   surgical emergencies (e.g., appendicitis) cannot be excluded

-   the patient is pregnant

-   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 and vomiting, or high fever;
    and

-   the patient has a tubo-ovarian abscess

Many practitioners have preferred to hospitalize adolescent women whose
condition is diagnosed as acute PID. No evidence is available suggesting
that adolescents benefit from hospitalization for treatment of PID.
Younger women with mild-to-moderate acute PID have similar outcomes with
either outpatient therapy or inpatient therapy. Further, clinical
response to outpatient treatment is similar among younger and older
women. The decision to hospitalize adolescents with acute PID should be
based on the same criteria used for older women. Whether women in their
later reproductive years benefit from hospitalization for treatment of
PID also is unclear, although women aged [\>]{.underline}35 years who
are hospitalized with PID are more likely than younger women to have a
complicated clinical course.

**Parenteral Treatment**

For women with PID of mild or moderate severity, parenteral and oral
therapy appears to have similar clinical efficacy. Many randomized
trials have demonstrated the efficacy of both parenteral and oral
regimens. In the majority of clinical trials, parenteral treatment for
at least 48 hours has been used after the patient has demonstrated
substantial clinical improvement. Clinical experience should guide
decisions regarding transition to oral therapy, which usually can be
initiated within 24 hours of clinical improvement. The majority of
clinicians recommend at least 24 hours of direct inpatient observation
for patients who have tubo-ovarian abscesses.

***Recommended Parenteral Regimen A***

-   **Cefotetan** 2 g intravenously (IV) every 12 hours

> **OR**

-   **Cefoxitin** 2 g IV every 6 hours

> ***PLUS***

-   **Doxycycline** 100 mg orally or IV every 12 hours

**Note**: Because of the pain associated with infusion, doxycycline
should be administered orally when possible, even when the patient is
hospitalized. Oral and IV administration of doxycycline provide similar
bioavailability.

Parenteral therapy may be discontinued 24 hours after a patient improves
clinically, and oral therapy with doxycycline (100 mg twice a day)
should continue to complete 14 days of therapy. When tubo-ovarian
abscess is present, many health-care providers use clindamycin or
metronidazole with doxycycline for continued therapy, rather than
doxycycline alone, because it provides more effective anaerobic
coverage.

Clinical data are limited regarding the use of other second- or
third-generation cephalosporins (e.g., ceftizoxime, cefotaxime, and
ceftriaxone), which also might be effective therapy for PID and may
replace cefotetan or cefoxitin. However, these cephalosporins are less
active than cefotetan or cefoxitin against anaerobic bacteria.

***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 may be substituted.

Although use of a single daily dose of gentamicin has not been evaluated
for the treatment of PID, it is efficacious in analogous situations.
Parenteral therapy can be discontinued 24 hours after a patient improves
clinically; continuing oral therapy should consist of doxycycline 100 mg
orally twice a day or clindamycin 450 mg orally four times a day to
complete a total of 14 days of therapy. When tubo-ovarian abscess is
present, many health-care providers use clindamycin for continued
therapy, rather than doxycycline, because clindamycin provides more
effective anaerobic coverage.

***Alternative Parenteral Regimens***

Limited data support the use of other parenteral regimens, but the
following three regimens have been investigated in at least one clinical
trial, and they have broad spectrum coverage.

-   **Levofloxacin** 500 mg IV once daily\*

> **WITH OR WITHOUT**

-   **Metronidazole** 500 mg IV every 8 hours

> **OR**

-   **Ofloxacin** 400 mg IV every 12 hours\*

> **WITH OR WITHOUT**

-   **Metronidazole** 500 mg IV every 8 hours

> **OR**

-   **Ampicillin/Sulbactam** 3 g IV every 6 hours

> ***PLUS***

-   **Doxycycline** 100 mg orally or IV every 12 hours

\*Quinolones should not be used in persons with a history of recent
foreign travel or partners\' travel, infections acquired in California
or Hawaii, or infections acquired in other areas with increased
quinolone-resistant *Neisseria gonorrhoeae* (QRNG) prevalence.

IV ofloxacin has been investigated as a single agent; however, because
of concerns regarding its spectrum, metronidazole may be included in the
regimen. Levofloxacin is as effective as ofloxacin and may be
substituted; its single daily dosing makes it advantageous from a
compliance perspective. One trial demonstrated high short-term clinical
cure rates with azithromycin, either alone for 1 week (at least one IV
dose followed by oral therapy) or with a 12-day course of metronidazole.
Ampicillin/sulbactam plus doxycycline is effective coverage against *C.
trachomatis, N. gonorrhoeae*, and anaerobes and for patients who have
tubo-ovarian abscess.

**Oral Treatment**

Oral therapy can be considered for women with mild-to-moderately severe
acute PID, as the clinical outcomes among women treated with oral
therapy are similar to those treated with parenteral therapy. The
following regimens provide coverage against the frequent etiologic
agents of PID. Patients who do not respond to oral therapy within 72
hours should be reevaluated to confirm the diagnosis and should be
administered parenteral therapy on either an outpatient or inpatient
basis.

***Recommended Regimen A***

-   **Levofloxacin** 500 mg orally once daily for 14 days\*

> **OR**

-   **Ofloxacin** 400 mg orally twice daily for 14 days

> **WITH OR WITHOUT**

-   **Metronidazole** 500 mg orally twice a day for 14 days

\*Quinolones should not be used in persons with a history of recent
foreign travel or partners\' travel, infections acquired in California
or Hawaii, or infections acquired in other areas with increased QRNG
prevalence.

Oral ofloxacin has been investigated as a single agent in two clinical
trials, and it is effective against both *N. gonorrhoeae* and *C.
trachomatis*. Despite the results of these trials, lack of anaerobic
coverage with ofloxacin is a concern; the addition of metronidazole to
the treatment regimen provides this coverage. Levofloxacin is as
effective as ofloxacin and may be substituted. Azithromycin has been
demonstrated in one randomized trial to be an effective regimen for
acute PID. The addition of metronidazole should be considered, as
anaerobic organisms are suspected in the etiology of the majority of PID
cases. Metronidazole will also treat BV, which frequently is associated
with PID.

***Regimen B***

-   **Ceftriaxone** 250 mg intramuscularly (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

The optimal choice of a cephalosporin for Regimen B is unclear; although
cefoxitin has better anaerobic coverage, ceftriaxone has better coverage
against *N. gonorrhoeae*. Clinical trials have demonstrated that a
single dose of cefoxitin is effective in obtaining short-term clinical
response in women who have PID. However, the theoretical limitations in
cefoxitin\'s coverage of anaerobes might require the addition of
metronidazole to the treatment regimen). Metronidazole also will
effectively treat BV, which is frequently associated with PID. No data
have been published regarding the use of oral cephalosporins for the
treatment of PID. Limited data suggest that the combination of oral
metronidazole and doxycycline after primary parenteral therapy is safe
and effective.

***Alternative Oral Regimens***

Although information regarding other outpatient regimens is limited, one
other regimen has undergone at least one clinical trial and has broad
spectrum coverage. Amoxicillin/clavulanic acid and doxycycline was
effective in obtaining short-term clinical response in a single clinical
trial; however, gastrointestinal symptoms might limit compliance with
this regimen.

**Follow-Up**

Patients should demonstrate substantial clinical improvement (e.g.,
defervescence; reduction in direct or rebound abdominal tenderness; and
reduction in uterine, adnexal, and cervical motion tenderness) within 3
days after initiation of therapy. Patients who do not improve within
this period usually require hospitalization, additional diagnostic
tests, and surgical intervention.

If no clinical improvement has occurred within 72 hours after outpatient
oral or parenteral therapy (using the criteria for clinical improvement
described previously), an examination should be performed. Subsequent
hospitalization, parenteral therapy, and diagnostic evaluation,
including the consideration of diagnostic laparoscopy for alternative
diagnoses, are recommended in women without clinical improvement. Some
specialists also recommend rescreening for *C. trachomatis* and *N.
gonorrhoeae* 4-6 weeks after therapy is completed in women with
documented infection with these pathogens. All women diagnosed with
acute PID should be offered HIV testing.

**Management of Sex Partners**

Male sex partners of women with PID should be examined and treated if
they had sexual contact with the patient during the 60 days preceding
the patient\'s onset of symptoms. Evaluation and treatment are
imperative because of the risk for reinfection of the patient and the
strong likelihood of urethral gonococcal or chlamydial infection in the
sex partner. Male partners of women who have PID caused by *C.
trachomatis* and/or *N. gonorrhoeae* frequently are asymptomatic.

Sex partners should be treated empirically with regimens effective
against both of these infections, regardless of the etiology of PID or
pathogens isolated from the infected woman. Even in clinical settings in
which only women are treated, arrangements should be made to provide
care for male sex partners of women who have PID. When providing care
for male sex partners is not feasible, health-care providers should
ensure that sex partners are referred for appropriate treatment.

**Prevention**

Prevention of chlamydial infection by screening and treating high-risk
women reduces the incidence of PID. Theoretically, the majority of cases
of PID can be prevented by screening all women or those determined to be
at high risk (based on age or other factors) by using DNA amplification
on cervical specimens (in women receiving pelvic examinations) and on
urine specimens (in women not undergoing examinations). Although
bacterial vaginosis is associated with PID, whether the incidence of PID
can be reduced by identifying and treating women with BV is unclear.

**Special Considerations**

**Pregnancy**

Because of the high risk for maternal morbidity and preterm delivery,
pregnant women who have suspected PID should be hospitalized and treated
with parenteral antibiotics.

**HIV Infection**

Differences in the clinical manifestations of PID between HIV-infected
women and HIV-negative women have not been well-delineated. In previous
observational studies, HIV-infected women with PID were more likely to
require surgical intervention. More comprehensive observational and
controlled studies (published since the 2002 STD Treatment Guidelines)
have demonstrated that HIV-infected women with PID had similar symptoms
when compared with uninfected controls. They were more likely to have a
tubo-ovarian abscess but responded equally well to standard parenteral
and oral antibiotic regimens when compared with HIV-negative women. The
microbiologic findings for HIV-positive and HIV-negative women were
similar, except HIV-infected women had higher rates of concomitant *M.
hominis*, candida, streptococcal, and HPV infections and HPV-related
cytologic abnormalities. Whether the management of immunodeficient
HIV-infected women with PID requires more aggressive interventions
(e.g., hospitalization or parenteral antimicrobial regimens) has not
been determined.

**IUD**

Intrauterine contraceptive devices (IUDs) are becoming a popular
contraceptive choice for women. Both levonorgestrel- and
copper-containing devices are marketed in the United States. The risk of
PID associated with IUD use is primarily confined to the first 3 weeks
after insertion and is uncommon thereafter. Given the popularity of
IUDs, practitioners might encounter PID in IUD users. No evidence
suggests that IUDs should be removed in women diagnosed with acute PID.
However, caution should be exercised if the IUD remains in place, and
close clinical follow-up is mandatory. The rate of treatment failure and
recurrent PID in women continuing to use an IUD is unknown. No data
exist on antibiotic selection and treatment outcomes according to type
of IUD (e.g., copper or levonorgestrel).

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is not specifically stated for each
recommendation.

Throughout the 2006 guideline document, the evidence used as the basis
for specific recommendations is discussed briefly. More comprehensive,
annotated discussions of such evidence will appear in background papers
that will be published in a supplement issue of the journal *Clinical
Infectious Diseases*.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Improved accurate diagnosis of pelvic inflammatory disease (PID)

-   Reduction in damage to reproductive health of women by PID (e.g.,
    tubal infertility, ectopic pregnancy)

-   Prevention of transmission of gonococcal or chlamydial infections to
    sex partners

-   Prevention of maternal morbidity and preterm delivery in pregnant
    women with PID

**Subgroups Most Likely to Benefit**

-   Pregnant women

-   Women with PID who wish to become pregnant in the future

#### POTENTIAL HARMS

-   Doxycycline is associated with pain during infusion

-   Amoxicillin/clavulanic acid plus doxycycline can cause
    gastrointestinal symptoms

-   The rate of treatment failure and recurrent pelvic inflammatory
    disease (PID) in women continuing to use an intrauterine
    contraceptive device (IUD) is unknown.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   These recommendations were developed in consultation with public-
    and private-sector professionals knowledgeable in the treatment of
    patients with sexually transmitted diseases (STDs). The
    recommendations are applicable to various patient-care settings,
    including family planning clinics, private physicians\' offices,
    managed care organizations, and other primary-care facilities.

-   These recommendations are meant to serve as a source of clinical
    guidance: health-care providers should always consider the
    individual clinical circumstances of each person in the context of
    local disease prevalence. These guidelines focus on the treatment
    and counseling of individual patients and do not address other
    community services and interventions that are important in STD/human
    immunodeficiency virus (HIV) prevention.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Personal Digital Assistant (PDA) Downloads

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Staying Healthy

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Centers for Disease Control and Prevention, Workowski KA, Berman SM.
Pelvic inflammatory disease. Sexually transmitted diseases treatment
guidelines 2006 \[published errata appear in MMWR Morb Mortal Wkly Rep
2006 Sep 15;55(36):997\]. MMWR Morb Mortal Wkly Rep 2006 Aug
4;55(RR-11):56-61. \[222 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

1993 (revised 2006 Aug 4)

#### GUIDELINE DEVELOPER(S)

Centers for Disease Control and Prevention - Federal Government Agency
\[U.S.\]

#### GUIDELINE DEVELOPER COMMENT

These guidelines for the treatment of persons who have sexually
transmitted diseases (STDs) were developed by CDC after consultation
with a group of professionals knowledgeable in the field of STDs who met
in Atlanta, Georgia, during April 19--21, 2005.

#### SOURCE(S) OF FUNDING

United States Government

#### GUIDELINE COMMITTEE

Not stated

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Chairpersons*: David Atkins, MD, Agency for Healthcare Research and
Quality, Rockville, Maryland; Kimberly A. Workowski, MD, National Center
for HIV, STD, and TB Prevention, CDC, and Emory University, Atlanta, GA

*Presenters*: Heidi Bauer, MD, California Sexually Transmitted Disease
Control Branch, Oakland, California; Emily J. Erbelding, MD, Johns
Hopkins University School of Medicine, Baltimore, Maryland; William M.
Geisler, MD, Department of Medicine, University of Alabama, Birmingham,
Alabama; Margaret Hammerschlag, MD, State University of New York,
Downstate Medical Center, Brooklyn, New York; Peter Leone, MD,
University of North Carolina School of Medicine, Chapel Hill, North
Carolina; Jenne Marrazzo, MD, University of Washington, Harborview
Medical Center, Seattle, Washington; Kenneth Hugh Mayer, MD, Brown
University Medical School, Providence, Rhode Island; Pablo Sanchez, MD,
University of Texas Southwestern Medical Center, Dallas, Texas; Bradley
Stoner, MD, PhD, Washington University, St. Louis, Missouri; Anna Wald,
MD, University of Washington, Harborview Medical Center, Seattle,
Washington; George Wendel, MD, University of Texas Southwestern Medical
School, Dallas, Texas; Karen Wendel, MD, University of Oklahoma Health
Science Center, Oklahoma City, Oklahoma; Harold C. Wiesenfeld, MD,
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

*Moderators*: Willard Cates, Jr., MD, Family Health International,
Durham, North Carolina; King K. Holmes, MD, PhD, University of
Washington, Harborview Medical Center, Seattle, Washington; David
Martin, MD, Louisiana State University Medical Center, New Orleans,
Louisiana

*Rapporteurs*: Hunter Handsfield, MD, National Center for HIV, STD, and
TB Prevention, CDC, Atlanta, Georgia, University of Washington, Seattle,
Washington; William McCormack, MD, State University of New York Health
Science Center, Brooklyn, New York; Anne Rompalo, MD, Johns Hopkins
School of Medicine, Baltimore, Maryland

*Consultants*: Michael Augenbraun, MD, State University of New York
Health Science Center, Brooklyn, New York; Gail Bolan, MD, California
Department of Health, Oakland, California; Carolyn Deal, PhD, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland; Kenneth H. Fife, MD, PhD, Indiana University
School of Medicine, Indianapolis, Indiana; J. Dennis Fortenberry, MD,
Indiana University School of Medicine, Indianapolis, Indiana; Edward
Hook, III, MD, Department of Medicine, University of Alabama,
Birmingham, Alabama; Franklyn Judson, MD, University of Colorado
Department of Medicine and Preventive Medicine, Denver, Colorado; Alice
A. Kraman, PharmD; Emory Healthcare, Atlanta, Georgia; Roberta B. Ness,
MD, University of Pittsburgh Department of Medicine, Pittsburgh,
Pennsylvania; Paul Nyirjesy, MD, Drexel University College of Medicine,
Philadelphia, Pennsylvania; Jeffrey Peipert, MD, Women and Infants
Hospital, Providence, Rhode Island; Jane R. Schwebke, MD, Department of
Medicine, University of Alabama, Birmingham, Alabama; Mary Ann Shafer,
MD, University of California, San Francisco Department of Medicine, San
Francisco, California; David Soper, MD, Medical University of South
Carolina, Charleston, South Carolina; Lawrence Stanberry, MD, PhD,
University of Texas Medical Branch, Galveston, Texas; Heather Watts, MD,
National Institute of Child Health and Development, National Institutes
of Health, Bethesda, Maryland; Jonathan M. Zenilman, MD, Johns Hopkins
Bayview Medical Center, Baltimore, Maryland

*Liaison Participants*: Joanne Armstrong, MD, Women\'s Health, Aetna,
Sugar Land, Texas; James R. Allen, MD, American Social Health
Association, Durham, North Carolina; Margaret J. Blythe, MD, American
Academy of Pediatrics, Indianapolis, Indiana; Sherry R. Crump, MD,
American College of Preventive Medicine, Atlanta, GA; Carolyn D. Deal,
PhD, National Institutes of Health, Bethesda, Maryland; Jordon
Dimitrakov, MD, PhD, American Urological Association, Boston,
Massachusetts; Mark FitzGerald, MD, British Association for Sexual
Health and HIV, Southampton, United Kingdom; Edward Harrison, National
Commission on Correctional Health Care, Chicago, Illinois; Edward W.
Hook, III, MD, Infectious Disease Society of America, Birmingham,
Alabama; Michel Janier, MD, PhD, International Union Against Sexually
Transmitted Infections Europe, Paris, France; Abe Macher, MD, HIV/AIDS
Bureau, Rockville, Maryland; Francis J. Ndowa, MD, World Health
Organization, Geneva, Switzerland; Jeffrey F. Peipert, MD, American
College of Obstetricians and Gynecologists, Providence, Rhode Island;
Kees A. Rietmeijer, MD, PhD, Denver Public Health Department, Denver,
Colorado; Richard Rothman, MD, American College of Emergency Physicians,
Baltimore, Maryland; David Soper, MD, Infectious Diseases Society for
Obstetrics and Gynecology, Charleston, South Carolina; Litjen Tan, PhD,
American Medical Association, Chicago, Illinois; Bruce Trigg, MD,
National Coalition for Sexually Transmitted Disease Directors,
Albuquerque, New Mexico; Julia Valderrama, MD, Pan American Health
Organization, Washington, DC; Tom Wong, MD, Public Health Agency of
Canada, Ottawa, Ontario, Canada; Miriam Zieman, MD, Association of
Reproductive Health Professionals, Atlanta, Georgia

*CDC, Division of Sexually Transmitted Disease Prevention Treatment
Guidelines 2006 Project. Coordinator*: Kimberly A. Workowski, MD,
National Center for HIV, STD, and TB Prevention, CDC, and Emory
University, Atlanta, GA

*Project Manager*: Donald F. Dowda, ORISE, Oakridge, Tennessee; Richard
Voigt, National Center for HIV, STD, and TB Prevention, CDC, Atlanta,
Georgia

*Co-Moderators*: Lyn Finelli, Ph.D., DSTDP; Robert Johnson, M.D., DSTDP;
Lauri Markowitz, M.D., DSTDP

*CDC Presenters*: Joanna Buffington, MD, National Center for Infectious
Diseases; Eileen Dunne, MD, National Center for HIV, STD, and TB
Prevention, CDC, Atlanta, Georgia; Matthew Hogben, PhD, National Center
for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Emily Koumans,
MD, National Center for HIV, STD, and TB Prevention, CDC, Atlanta,
Georgia; Hershel Lawson, MD, National Center for Chronic Disease
Prevention and Health Promotion, Atlanta, Georgia; Catherine McLean, MD,
National Center for HIV, STD, and TB Prevention, Atlanta, Georgia;
Juliette Morgan, MD, National Center for Infectious Diseases, CDC,
Atlanta, Georgia; Lori Newman, MD, National Center for HIV, STD, and TB
Prevention, CDC, Atlanta, Georgia; Madeline Sutton, MD, National Center
for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia

*CDC Consultants*: Sevgi O. Aral, PhD, Stuart M. Berman, MD, John
Douglas, MD, Susan J. DeLisle, Kathleen Ethier, PhD, National Center for
HIV, STD, and TB Prevention, CDC, Atlanta, Georgia; Kevin Fenton, MD,
National Center for HIV, Hepatitis, Sexually Transmitted Diseases and
Tuberculosis Prevention, CDC, Atlanta, Georgia; John Moran, MD, National
Immunization Program, CDC, Atlanta, Georgia; Julia Schillinger, MD,
National Center for HIV, STD, and TB Prevention, CDC, Atlanta, Georgia

*Support Staff*: Valerie Barner, Winda Graves, Garrett Mallory, Deborah
McElroy, National Center for HIV, STD, and TB Prevention, CDC, Atlanta,
Georgia; Eboney Walker, NAI Personnel, Washington, DC

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

This guideline updates a previous version: Centers for Disease Control
and Prevention. Pelvic inflammatory disease. Sexually transmitted
diseases treatment guidelines. MMWR Recomm Rep 2002 May
10;51(RR-6):48-52.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the Centers for Disease Control and
Prevention (CDC) Web site:

-   [HTML Format](http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5511a1.htm)

-   [Portable Document Format
    (PDF)](http://www.cdc.gov/mmwr/PDF/rr/rr5511.pdf)

Print copies: Available from the Centers for Disease Control and
Prevention, MMWR, Atlanta, GA 30333. Additional copies can be purchased
from the Superintendent of Documents, U.S. Government Printing Office,
Washington, DC 20402-9325; (202) 783-3238.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   Workowski KA, Levine WC, Wasserheit JN. U.S. Centers for Disease
    Control and Prevention guidelines for the treatment of sexually
    transmitted diseases: an opportunity to unify clinical and public
    health practice. Ann Intern Med. 2002 Aug 20;137(4):255-62.
    Electronic copies: Available through [Annals of Internal Medicine
    Online](http://www.annals.org/issues/v137n4/full/200208200-00010.html).

-   The CDC Sexually Transmitted Diseases Treatment Guidelines 2004 for
    PDA or Palm OS. Available from the [CDC National Prevention
    Information Network (NPIN) Web
    site](http://www.cdcnpin.org/scripts/std/pda.asp).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on August 19, 2002. This summary was
updated by ECRI on October 12, 2006. This summary was updated by ECRI
Institute on October 3, 2007 following the U.S. Food and Drug
Administration (FDA) advisory on Rocephin (ceftriaxone sodium). This
summary was updated by ECRI Institute on July 28, 2008 following the
U.S. Food and Drug Administration advisory on fluoroquinolone
antimicrobial drugs.

#### COPYRIGHT STATEMENT

No copyright restrictions apply.

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008